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Childhood onset dystonia, chorea or related movement disorder v4.1 Eleanor Williams Panel version 4.0 has been signed off on 2024-05-01
Childhood onset dystonia, chorea or related movement disorder v4.0 Eleanor Williams promoted panel to version 4.0
Childhood onset dystonia, chorea or related movement disorder v3.78 CENPF Arina Puzriakova Phenotypes for gene: CENPF were changed from Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome to Stromme syndrome, OMIM:243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome
Childhood onset dystonia, chorea or related movement disorder v3.77 ACBD6 Arina Puzriakova Phenotypes for gene: ACBD6 were changed from Neurodevelopmental disorder, MONDO:0700092 to Neurodevelopmental disorder with progressive movement abnormalities, OMIM:620785
Childhood onset dystonia, chorea or related movement disorder v3.74 PRNP Arina Puzriakova changed review comment from: Comment on list classification: Given that the age of onset associated with the multiple phenotypes related to this gene, inclusion on this panel should be reviewed by the GMS specialist group.; to: Comment on list classification: Given that the age of onset associated with the multiple phenotypes related to this gene is almost always in adulthood and poses risk of incidental findings, inclusion of PRNP on this panel should be reviewed by the GMS specialist group.
Childhood onset dystonia, chorea or related movement disorder v3.74 PRNP Arina Puzriakova Classified gene: PRNP as Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v3.74 PRNP Arina Puzriakova Added comment: Comment on list classification: Given that the age of onset associated with the multiple phenotypes related to this gene, inclusion on this panel should be reviewed by the GMS specialist group.
Childhood onset dystonia, chorea or related movement disorder v3.74 PRNP Arina Puzriakova Gene: prnp has been classified as Green List (High Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.70 HSD17B10 Arina Puzriakova changed review comment from: Comment on list classification: Upgrading from Red to Amber but there is sufficient evidence to promote this gene to Green at the next GMS panel update - choreoathetoid movements and dystonia can be reported features of HSD10 disease (PMID: 12555940; 22132097; 26950678; 31654490); to: Comment on list classification: Upgrading from Red to Amber but there is sufficient evidence to promote this gene to Green at the next GMS panel update - choreoathetoid movements and dystonia can be reported features of HSD10 disease (PMID: 12555940; 22132097; 26950678; 27295195; 31654490)
Childhood onset dystonia, chorea or related movement disorder v3.70 HSD17B10 Arina Puzriakova Classified gene: HSD17B10 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v3.70 HSD17B10 Arina Puzriakova Added comment: Comment on list classification: Upgrading from Red to Amber but there is sufficient evidence to promote this gene to Green at the next GMS panel update - choreoathetoid movements and dystonia can be reported features of HSD10 disease (PMID: 12555940; 22132097; 26950678; 31654490)
Childhood onset dystonia, chorea or related movement disorder v3.70 HSD17B10 Arina Puzriakova Gene: hsd17b10 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.65 ASL Eleanor Williams changed review comment from: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy.

The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g.

PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries. No phenotype information is given. They also found a complete homologue of this gene on chr 22 which is predicted to encode an immunoglobulin-lambda-like mRNA.

PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. Ataxia is not mentioned as a phenotypic feature.

PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients (likely founder mutation); c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient. 7/10 patients are reported to show spasticity although it is not reporterd whether they all shared the same founder variant in ASL.

More recent retrospectives show that ataxia is reported in approx. 10% of individuals with Argininosuccinic aciduria. 2 cases with ataxia and ASL variant identified are reported.

PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53  years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 4 were reported to show tremor/dystonia, with this phenotype present at ages 9, 11, 24 and 25 years of age. Homozygous or compound het ASL variants were recorded in 25/60 patients including 3 out of the 4 patients with tremor/dystonia (patients 4,9 and 25 with c.719-2A>G; c.857A>G, c.1153C>T; c.1153C>T and c.437G>A; c.446+1G>A respectively). Genotype data was not available for other patients. Although patient 4 from this study and patient 9 from the Baruteau et al 2017 study share the same genotype and are both male, their phenotypic descriptions differ so assuming here that they are not the same patient.

PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Tremors or dystonia were reported in 4 individuals (1,4,9 and 25). All were diagnosed before the age of 3 although it is not stated at what age the tremors/dystonia were first noted. The first 3 of these patients had homozygous or compound het variants in ASL identified (c.35G>A;c.35G>A, c.377G>A;c.377G>A and c.719-2A>G, c.857A>G respectively).

(PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. ); to: Argininosuccinic aciduria (ASA) is caused by homozygous mutation in the gene encoding argininosuccinate lyase (ASL). Onset is typically in the neonatal period or in late infancy.

The association of biallelic variants in ASL and the phenotype of Argininosuccinic aciduria is well established. e.g.
PMID: 12384776 - Linnebank et al 2002 - homozygous/compound het variants in ASL in 27 unrelated individuals of different ancestries, PMID: 17326097 - Trevisson et al 2007 - report homozygous/compound het variants in ASL in 12 Italian patients with ASA. PMID: 29326055 - AlTassan et al 2018 - a retrospective review of 54 Saudi Arabian patients with ASA from January 2000 to December 2015. 35 patients (63%) had genetic data available all with variants in the ASL gene; c.1060C > T; p.(Gln354*) in 26 patients (likely founder mutation); c.556C > T; p.(Arg186Trp) in 7 patients, c.602+1G > T in one patient and 1062+5G > C in one patient.

More recent retrospectives show that tremors and/or dystonia is reported in some individuals with Argininosuccinic aciduria. 6 cases with ataxia and ASL variant identified are reported.

PMID: 38044746 - Gurung et al 2023 - conducted a UK national multicentre retrospective study assessing the movement disorder phenotype in ASA patients from July 2015 to June 2022. 60 patients were studied with a median age of 12.7 years (range: 6 months to 53  years). 17 (28%) individuals had ASA with neurodegenerative-related symptoms, movement disorder, hypotonia/fatigue and abnormal behaviour. Of these 4 were reported to show tremor/dystonia, with this phenotype present at ages 9, 11, 24 and 25 years of age. Homozygous or compound het ASL variants were recorded in 25/60 patients including 3 out of the 4 patients with tremor/dystonia (patients 4,9 and 25 with c.719-2A>G; c.857A>G, c.1153C>T; c.1153C>T and c.437G>A; c.446+1G>A respectively). Genotype data was not available for other patients. Although patient 4 from this study and patient 9 from the Baruteau et al 2017 study share the same genotype and are both male, their phenotypic descriptions differ so assuming here that they are not the same patient.

PMID: 28251416 - Baruteau et al 2017 - conducted a retrospective and prospective analysis of patients in the UK with ASA from March 2013 - December 2015. Tremors or dystonia were reported in 4 individuals (1,4,9 and 25). All were diagnosed before the age of 3 although it is not stated at what age the tremors/dystonia were first noted. The first 3 of these patients had homozygous or compound het variants in ASL identified (c.35G>A;c.35G>A, c.377G>A;c.377G>A and c.719-2A>G, c.857A>G respectively).

(PMID: 36994644 - Elkhateeb et al 2023 - characterise the incidence of epilepsy in patients with ASA. )
Childhood onset dystonia, chorea or related movement disorder v3.65 ASL Eleanor Williams Classified gene: ASL as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v3.65 ASL Eleanor Williams Added comment: Comment on list classification: Promoting this gene to amber, with a recommendation of green rating subject to GMS review. 6 patients with tremor and/or dystonia and variants identified in the ASL gene (from PMID: 38044746 - Gurung et al 2023 and PMID: 28251416 - Baruteau et al 2017).
Childhood onset dystonia, chorea or related movement disorder v3.65 ASL Eleanor Williams Gene: asl has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.61 SHQ1 Sarah Leigh Classified gene: SHQ1 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v3.61 SHQ1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia, chorea or related movement disorder v3.61 SHQ1 Sarah Leigh Gene: shq1 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.60 SHQ1 Sarah Leigh commented on gene: SHQ1: SHQ1 variants are associated with Neurodevelopmental disorder with dystonia and seizures, OMIM:619922 and Dystonia 35, childhood-onset, OMIM:619921, but not with a phenotype in Gen2Phen. At least 10 SHQ1 variants have been reported (PMIDs: 29178645 34542157; 36810590; 36847845) in eight unrelated cases. The phenotypic features were dystonia (7/7 cases examined), hypotonia (6/7 cases examined), intellectual disability (7/8 cases examined), and seizures (in 4/6 cases and 2 further unrelated cases where remaining affected siblings did not have seizures (1/2 and 3/4)(PMID: 36847845).
Childhood onset dystonia, chorea or related movement disorder v3.57 SHQ1 Sarah Leigh Classified gene: SHQ1 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v3.57 SHQ1 Sarah Leigh Gene: shq1 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.53 ARX Sarah Leigh changed review comment from: A review by Eldar Dedic (Independent Clinical Genetics Consultant)
Kwong, et al. (2019, PMID: 31324350) presented a Chinese family with infantile epileptic dyskinetic encephalopathy. The whole-exome-sequencing revealed ARX c.989G>A (p.Arg330His) in 13 years of age affected proband (who also suffered from dystonia), as well as in his unaffected mother and sister. Proband also had a healthy older brother who did not carry the variant. The proband’s muscle whole mitochondrial DNA analysis did not show the presence of a pathogenic variant. - Please note that ARX c.989G>A (p.Arg330His) was absent from gnomAD v2.1.1 as of December 2021 Gorman, et al. (2018, PMID: 29778428) presented 2 years of age Ohtahara syndrome male case of Romanian origin. Whole-exome-sequencing revealed ARX c.1600G>C (p.Ala534Pro) variant in a patient (who also had dystonia) and in his healthy mother (who was a low-level mosaic). The proband was negative for chromosomal array testing and had a normal brain MRI. - Please note that ARX c.1600G>C (p.Ala534Pro) was absent from gnomAD v2.1.1 as of December 2021 Charzewska, et al. (2013, PMID: 23657928) presented a family with intellectual disability and dystonia. Sequencing of ARX revealed the presence of c.4A>T (p.Ser2Cys) variant in 4 affected males (including 2 who had onset of dystonia at 2nd day of life and 12 years of age, respectively) and in 5 female carriers. - Please note that ARX c.4A>T (p.Ser2Cys) was absent from gnomAD v2.1.1 as of December 2021 Breen, et al. (2018, PMID: 29343471) presented 12 years of age male case with intellectual disability and hand dystonia. The ARX c.426_458dup (p.Gly143_Ala153dup) variant has been reported in the proband, his cousin and maternal uncle from Pakistan, both of which had hand dystonia, as well as in his unaffected mother. The patient had whole-exome-sequencing as one of the previous tests carried out. - Please note that ARX c.426_458dup (p.Gly143_Ala153dup) was absent from gnomAD v2.1.1 as of December 2021; to: A review by Eldar Dedic (Independent Clinical Genetics Consultant):
Kwong, et al. (2019, PMID: 31324350) presented a Chinese family with infantile epileptic dyskinetic encephalopathy. The whole-exome-sequencing revealed ARX c.989G>A (p.Arg330His) in 13 years of age affected proband (who also suffered from dystonia), as well as in his unaffected mother and sister. Proband also had a healthy older brother who did not carry the variant. The proband’s muscle whole mitochondrial DNA analysis did not show the presence of a pathogenic variant. - Please note that ARX c.989G>A (p.Arg330His) was absent from gnomAD v2.1.1 as of December 2021 Gorman, et al. (2018, PMID: 29778428) presented 2 years of age Ohtahara syndrome male case of Romanian origin. Whole-exome-sequencing revealed ARX c.1600G>C (p.Ala534Pro) variant in a patient (who also had dystonia) and in his healthy mother (who was a low-level mosaic). The proband was negative for chromosomal array testing and had a normal brain MRI. - Please note that ARX c.1600G>C (p.Ala534Pro) was absent from gnomAD v2.1.1 as of December 2021 Charzewska, et al. (2013, PMID: 23657928) presented a family with intellectual disability and dystonia. Sequencing of ARX revealed the presence of c.4A>T (p.Ser2Cys) variant in 4 affected males (including 2 who had onset of dystonia at 2nd day of life and 12 years of age, respectively) and in 5 female carriers. - Please note that ARX c.4A>T (p.Ser2Cys) was absent from gnomAD v2.1.1 as of December 2021 Breen, et al. (2018, PMID: 29343471) presented 12 years of age male case with intellectual disability and hand dystonia. The ARX c.426_458dup (p.Gly143_Ala153dup) variant has been reported in the proband, his cousin and maternal uncle from Pakistan, both of which had hand dystonia, as well as in his unaffected mother. The patient had whole-exome-sequencing as one of the previous tests carried out. - Please note that ARX c.426_458dup (p.Gly143_Ala153dup) was absent from gnomAD v2.1.1 as of December 2021
Childhood onset dystonia, chorea or related movement disorder v3.53 ARX Sarah Leigh commented on gene: ARX: A review by Eldar Dedic (Independent Clinical Genetics Consultant)
Kwong, et al. (2019, PMID: 31324350) presented a Chinese family with infantile epileptic dyskinetic encephalopathy. The whole-exome-sequencing revealed ARX c.989G>A (p.Arg330His) in 13 years of age affected proband (who also suffered from dystonia), as well as in his unaffected mother and sister. Proband also had a healthy older brother who did not carry the variant. The proband’s muscle whole mitochondrial DNA analysis did not show the presence of a pathogenic variant. - Please note that ARX c.989G>A (p.Arg330His) was absent from gnomAD v2.1.1 as of December 2021 Gorman, et al. (2018, PMID: 29778428) presented 2 years of age Ohtahara syndrome male case of Romanian origin. Whole-exome-sequencing revealed ARX c.1600G>C (p.Ala534Pro) variant in a patient (who also had dystonia) and in his healthy mother (who was a low-level mosaic). The proband was negative for chromosomal array testing and had a normal brain MRI. - Please note that ARX c.1600G>C (p.Ala534Pro) was absent from gnomAD v2.1.1 as of December 2021 Charzewska, et al. (2013, PMID: 23657928) presented a family with intellectual disability and dystonia. Sequencing of ARX revealed the presence of c.4A>T (p.Ser2Cys) variant in 4 affected males (including 2 who had onset of dystonia at 2nd day of life and 12 years of age, respectively) and in 5 female carriers. - Please note that ARX c.4A>T (p.Ser2Cys) was absent from gnomAD v2.1.1 as of December 2021 Breen, et al. (2018, PMID: 29343471) presented 12 years of age male case with intellectual disability and hand dystonia. The ARX c.426_458dup (p.Gly143_Ala153dup) variant has been reported in the proband, his cousin and maternal uncle from Pakistan, both of which had hand dystonia, as well as in his unaffected mother. The patient had whole-exome-sequencing as one of the previous tests carried out. - Please note that ARX c.426_458dup (p.Gly143_Ala153dup) was absent from gnomAD v2.1.1 as of December 2021
Childhood onset dystonia, chorea or related movement disorder v3.43 OCLN Sarah Leigh Classified gene: OCLN as Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v3.43 OCLN Sarah Leigh Added comment: Comment on list classification: To date, there are no reports of dystonia, chorea or other movement disorders associated with OCLN variants (PMID: 20727516;34704946;34573918;28386946). Therefore this gene should not be green on this panel.
Childhood onset dystonia, chorea or related movement disorder v3.43 OCLN Sarah Leigh Gene: ocln has been classified as Green List (High Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.42 KCNQ2 Sarah Leigh Classified gene: KCNQ2 as Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v3.42 KCNQ2 Sarah Leigh Added comment: Comment on list classification: There is only one case (PMID:12742592), of dystonia in a patient carrying a KCNQ2 variant. To date, there are no reports of relevant chorea or other movement disorders associated with KCNQ2 variants (PMID: 22275249;22926866;23621294;31418850;35780567;33794528). Therefore this gene should not be green on this panel.
Childhood onset dystonia, chorea or related movement disorder v3.42 KCNQ2 Sarah Leigh Gene: kcnq2 has been classified as Green List (High Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.38 L2HGDH Achchuthan Shanmugasundram changed review comment from: PMID:15824270 - A 15 year-old boy with L-2-hydroxyglutaric aciduria was reported with early infantile-onset progressive psychomotor regression, mild choreodystonia affecting the distal part of the upper limbs, pyramidal signs, and epilepsy.

PMID:18780161 - Of seven patients from three unrelated Tunisian families with L-2-hydroxyglutaric aciduria and with homozygous variants in L2HGDH gene, three patients from two different families had dystonia.

PMID:24753671 - Two siblings were reported with dystonia diagnosed by classical neuroimaging findings with elevated urinary 2 hydroxyglutaric acid.; to: PMID:15824270 - A 15 year-old boy with L-2-hydroxyglutaric aciduria was reported with early infantile-onset progressive psychomotor regression, mild choreodystonia affecting the distal part of the upper limbs, pyramidal signs, and epilepsy.

PMID:18780161 - Of seven patients from three unrelated Tunisian families with L-2-hydroxyglutaric aciduria and with homozygous variants in L2HGDH gene, three patients from two different families had dystonia. The age of onset of the disorder in these patients is around six years.

PMID:24753671 - Two siblings (13 and 16 years of age with disease onset at 10 years of age) were reported with dystonia diagnosed by classical neuroimaging findings with elevated urinary 2 hydroxyglutaric acid.
Childhood onset dystonia, chorea or related movement disorder v3.38 SYT1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark, there are four unrelated cases with childhood-onset dystonia as a feature of Baker-Gordon syndrome. Hence, this gene should be promoted to green rating at the next major update.; to: Comment on list classification: As reviewed by Zornitza Stark, there are four unrelated children with dystonia as a feature of Baker-Gordon syndrome. Hence, this gene should be promoted to green rating at the next major update.
Childhood onset dystonia, chorea or related movement disorder v3.38 SYT1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark, there are four unrelated cases with dystonia as a feature of Baker-Gordon syndrome. Hence, this gene should be promoted to green rating at the next major update.; to: Comment on list classification: As reviewed by Zornitza Stark, there are four unrelated cases with childhood-onset dystonia as a feature of Baker-Gordon syndrome. Hence, this gene should be promoted to green rating at the next major update.
Childhood onset dystonia, chorea or related movement disorder v3.36 SLC18A2 Achchuthan Shanmugasundram Classified gene: SLC18A2 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v3.36 SLC18A2 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there is sufficient evidence (at least four unrelated cases and functional evidence) available for the association of this gene to movement disorders including dystonia. Hence, this gene can be promoted to green rating at the next GMS review.
Childhood onset dystonia, chorea or related movement disorder v3.36 SLC18A2 Achchuthan Shanmugasundram Gene: slc18a2 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.35 SLC18A2 Achchuthan Shanmugasundram Phenotypes for gene: SLC18A2 were changed from Brain Dopamine Serotonin Vesicular Transport Disease (Other disorders of neurotransmitter metabolism); Vesicular monoamine transporter deficiency to ?Parkinsonism-dystonia, infantile, 2, OMIM:618049
Childhood onset dystonia, chorea or related movement disorder v3.33 SLC18A2 Achchuthan Shanmugasundram changed review comment from: PMID:23363473 - Eight children from an extended consanguineous Saudi Arabian family had a complex neurological disorder apparent since infancy. This disorder is characterised by abnormal movements, including parkinsonism, dystonia, and poor fine motor skills, as well as autonomic dysfunction, including abnormal sweating, cold extremities, and poor sleep. They were identified with a homozygous SLC18A2 variant (p.Pro387Leu). Functional evaluation showed that protein harbouring this variant has dramatically reduced activity than wild type protein, suggesting severe, but not complete loss of function as mechanism of action.

PMID:26497564 - Two male siblings from a consanguineous fancy was reported with a disorder comprising truncal hypotonia, a general paucity of movements, extrapyramidal signs and cognitive delay. They were identified with a homozygous SLC18A2 variant (p.Pro237His).; to: PMID:23363473 - Eight children from an extended consanguineous Saudi Arabian family had a complex neurological disorder apparent since infancy. This disorder is characterised by abnormal movements, including parkinsonism, dystonia, and poor fine motor skills, as well as autonomic dysfunction, including abnormal sweating, cold extremities, and poor sleep. They were identified with a homozygous SLC18A2 variant (p.Pro387Leu). Functional evaluation showed that protein harbouring this variant has dramatically reduced activity than wild type protein, suggesting severe, but not complete loss of function as mechanism of action.

PMID:26497564 - Two male siblings from a consanguineous family was reported with a disorder comprising truncal hypotonia, a general paucity of movements, extrapyramidal signs and cognitive delay. They were identified with a homozygous SLC18A2 variant (p.Pro237His).

PMID:31240161 - A child from a consanguineous family presented with hypotonia, mental disability, epilepsy, uncontrolled movements, and gastrointestinal problems and was identified with a homozygous SLC18A2 variant (p.Pro316Ala).

PMID:34078222 - A 6-month-old male infant who presented with developmental delay and suspected cerebral palsy was also diagnosed with infantile parkinsonism-dystonia-2 and was identified with the homozygous variant (p.Pro237His) reported in PMID:26497564.

This gene has been associated with relevant phenotypes in OMIM (PMID:618049), but not in Gene2Phenotype.
Childhood onset dystonia, chorea or related movement disorder v3.33 SLC18A2 Achchuthan Shanmugasundram commented on gene: SLC18A2: PMID:23363473 - Eight children from an extended consanguineous Saudi Arabian family had a complex neurological disorder apparent since infancy. This disorder is characterised by abnormal movements, including parkinsonism, dystonia, and poor fine motor skills, as well as autonomic dysfunction, including abnormal sweating, cold extremities, and poor sleep. They were identified with a homozygous SLC18A2 variant (p.Pro387Leu). Functional evaluation showed that protein harbouring this variant has dramatically reduced activity than wild type protein, suggesting severe, but not complete loss of function as mechanism of action.

PMID:26497564 - Two male siblings from a consanguineous fancy was reported with a disorder comprising truncal hypotonia, a general paucity of movements, extrapyramidal signs and cognitive delay. They were identified with a homozygous SLC18A2 variant (p.Pro237His).
Childhood onset dystonia, chorea or related movement disorder v3.33 TBC1D24 Achchuthan Shanmugasundram Classified gene: TBC1D24 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v3.33 TBC1D24 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are five unrelated cases reported with dystonia as a feature of the overall phenotype. Hence, this gene can be promoted to green rating at the next major update.
Childhood onset dystonia, chorea or related movement disorder v3.33 TBC1D24 Achchuthan Shanmugasundram Gene: tbc1d24 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.30 SYT1 Achchuthan Shanmugasundram changed review comment from: Comment on list classification: As reviewed by Zornitza Stark, there are four unrelated cases with dystonia as a feature of the SYT1-associated neurodevelopmental disorder. Hence, this gene should be promoted to green rating at the next major update.; to: Comment on list classification: As reviewed by Zornitza Stark, there are four unrelated cases with dystonia as a feature of Baker-Gordon syndrome. Hence, this gene should be promoted to green rating at the next major update.
Childhood onset dystonia, chorea or related movement disorder v3.30 SYT1 Achchuthan Shanmugasundram Classified gene: SYT1 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v3.30 SYT1 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there are four unrelated cases with dystonia as a feature of the SYT1-associated neurodevelopmental disorder. Hence, this gene should be promoted to green rating at the next major update.
Childhood onset dystonia, chorea or related movement disorder v3.30 SYT1 Achchuthan Shanmugasundram Gene: syt1 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.29 SQSTM1 Achchuthan Shanmugasundram Classified gene: SQSTM1 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v3.29 SQSTM1 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (three unrelated families) available for promoting this gene to green rating at the next major update.
Childhood onset dystonia, chorea or related movement disorder v3.29 SQSTM1 Achchuthan Shanmugasundram Gene: sqstm1 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.27 L2HGDH Achchuthan Shanmugasundram Classified gene: L2HGDH as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v3.27 L2HGDH Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there are four unrelated cases with dystonia as a feature of the condition and hence this gene can be promoted to green rating in the next GMS review.
Childhood onset dystonia, chorea or related movement disorder v3.27 L2HGDH Achchuthan Shanmugasundram Gene: l2hgdh has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.23 SLC30A9 Achchuthan Shanmugasundram Classified gene: SLC30A9 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v3.23 SLC30A9 Achchuthan Shanmugasundram Added comment: Comment on list classification: There are six unrelated families with childhood onset dystonia or choreoathetosis reported with biallelic variants in this gene. Hence, this gene can be promoted to Green at the next major update.
Childhood onset dystonia, chorea or related movement disorder v3.23 SLC30A9 Achchuthan Shanmugasundram Gene: slc30a9 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.22 SLC30A9 Achchuthan Shanmugasundram gene: SLC30A9 was added
gene: SLC30A9 was added to Childhood onset dystonia, chorea or related movement disorder. Sources: Literature
Mode of inheritance for gene: SLC30A9 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: SLC30A9 were set to 28334855; 34716203; 37041080
Phenotypes for gene: SLC30A9 were set to Birk-Landau-Perez syndrome, OMIM:617595
Review for gene: SLC30A9 was set to GREEN
Added comment: PMID:28334855 - Six patients from a large multigenerational Bedouin kindred had onset of different combinations of intellectual disability, muscle weakness, oculomotor apraxia, and nephropathy in early childhood and they were identified with a homozygous variant in SLC30A9 gene (c.1047_1049delGCA; p.A350del). The age of onset of movement disorder was around 1-2 years of age.

PMID:34716203 - A girl of African-American descent was identified with compound heterozygous variants in SLC30A9 gene (c.40delA & c.86_87dupCC) and was reported with a cerebrorenal syndrome. She presented around one year of age with microcephaly and global developmental delay. She also had bilateral sensorineural hearing loss and later developed dystonic movements affecting the whole body (onset was around 5-10 years of age).

PMID:37041080 - Eight individuals from four unrelated families were reported with SLC30A9-related disease and they presented with intellectual disability and progressive hyperkinetic movement disorder, associated with oculomotor apraxia and ptosis despite phenotypic variability. The two families of British Pakistani descent harboured homozygous c.1253G>T (p.Gly418Val) variant, Egyptian Palestinian family harboured homozygous c.1049delCAG (pAla350del) variant, while family of European Australian descent had compound heterozygous variants (c.1083dup/ p.Val362Cysfs*5, and c.1413A>G/ p.Ser471=). The age of onset of movement disorder in these patients ranged from around 1-2 years to 16 years of age.

This gene has been associated with relevant phenotypes in OMIM (MIM #617595), but not yet in Gene2Phenotype.
Sources: Literature
Childhood onset dystonia, chorea or related movement disorder v3.21 TMEM151A Achchuthan Shanmugasundram changed review comment from: Comment on list classification: There is sufficient evidence (more than 40 unrelated cases and supporting functional evidence) available in support of the association of this gene to PKD. Hence, this gene can be rated Green in the next major update.; to: Comment on list classification: There is sufficient evidence (more than 40 unrelated cases and supporting functional evidence) available in support of the association of this gene to PKD with onset in childhood/ adolescence. Hence, this gene can be rated Green in the next major update.
Childhood onset dystonia, chorea or related movement disorder v3.21 TMEM151A Achchuthan Shanmugasundram Classified gene: TMEM151A as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v3.21 TMEM151A Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (more than 40 unrelated cases and supporting functional evidence) available in support of the association of this gene to PKD. Hence, this gene can be rated Green in the next major update.
Childhood onset dystonia, chorea or related movement disorder v3.21 TMEM151A Achchuthan Shanmugasundram Gene: tmem151a has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.20 TMEM151A Achchuthan Shanmugasundram Phenotypes for gene: TMEM151A were changed from Episodic kinesigenic dyskinesia 3 to Episodic kinesigenic dyskinesia 3, OMIM:620245
Childhood onset dystonia, chorea or related movement disorder v3.18 TMEM151A Achchuthan Shanmugasundram changed review comment from: PMID:34518509 - Nine individuals from three unrelated Chines families with paroxysmal kinesigenic dyskinesia (PKD) were identified with autosomal dominant variants in TMEM151A gene. In addition, 8 unrelated patients (isolated cases) with sporadic occurrence of PKD were also identified with heterozygous variants, of which three patients inherited variants from an unaffected parent, suggesting incomplete penetrance. The age of onset of symptoms ranged between 9 and 15 years. In addition, supporting mouse model and in vitro functional assays suggested loss of function as the mechanism of disease.

PMID:34820915 - 29 PRRT2-negative Chinese patients from 25 families with PKD identified with 24 heterozygous variants in TMEM151A gene. The mean age of onset of symptoms was 12.93 years, with 13 patients reported with spontaneous remission of the disease around 21 years of age.

PMID:35587630 - De novo missense variant in TMEM151A was identified in a French man with PKD and he presented with brief attacks of dystonia after 16 years of age.

PMID:35707035 - Screening of patients with PRRT2-negative PKD and other movement disorders identified two novel variants in TMEM151A gene in two patients with PKD.

PMID:35727387 - Heterozygous missense variant was identified in four affected members of a 3-generation Chinese family with PKD and the variant segregated with the disorder in the family.


This gene has been associated with relevant phenotype in OMIM (MIM #620245), but not in Gene2Phenotype.; to: PMID:34518509 - Nine individuals from three unrelated Chines families with paroxysmal kinesigenic dyskinesia (PKD) were identified with autosomal dominant variants in TMEM151A gene. In addition, 8 unrelated patients (isolated cases) with sporadic occurrence of PKD were also identified with heterozygous variants, of which three patients inherited variants from an unaffected parent, suggesting incomplete penetrance. The age of onset of symptoms ranged between 9 and 15 years. In addition, supporting mouse model and in vitro functional assays suggested loss of function as the mechanism of disease.

PMID:34820915 - 29 PRRT2-negative Chinese patients from 25 families with PKD identified with 24 heterozygous variants in TMEM151A gene. The mean age of onset of symptoms was 12.93 years, with 13 patients reported with spontaneous remission of the disease around 21 years of age.

PMID:35587630 - De novo missense variant in TMEM151A was identified in a French man with PKD and he presented with brief attacks of dystonia after 16 years of age.

PMID:35707035 - Screening of patients with PRRT2-negative PKD and other movement disorders identified two novel variants in TMEM151A gene in two patients with PKD.

PMID:35727387 - Heterozygous missense variant was identified in four affected members of a 3-generation Chinese family with PKD and the variant segregated with the disorder in the family.

PMID:36724570 - Three patients presenting with PKD were identified with different TMEM151A variants.

This gene has been associated with relevant phenotype in OMIM (MIM #620245), but not in Gene2Phenotype.
Childhood onset dystonia, chorea or related movement disorder v3.17 TMEM151A Achchuthan Shanmugasundram reviewed gene: TMEM151A: Rating: GREEN; Mode of pathogenicity: None; Publications: 34518509, 34820915, 35587630, 35707035, 35727387; Phenotypes: Episodic kinesigenic dyskinesia 3, OMIM:620245; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Childhood onset dystonia, chorea or related movement disorder v3.17 TMEM151A Lucy Jackson gene: TMEM151A was added
gene: TMEM151A was added to Childhood onset dystonia, chorea or related movement disorder. Sources: NHS GMS
Mode of inheritance for gene: TMEM151A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: TMEM151A were set to (PMID: 34518509; 35707035; 36724570; 34820915)
Phenotypes for gene: TMEM151A were set to Episodic kinesigenic dyskinesia 3
Review for gene: TMEM151A was set to GREEN
Added comment: LOF variants have been shown to cause autosomal dominant Episodic kinesigenic dyskinesia 3
Sources: NHS GMS
Childhood onset dystonia, chorea or related movement disorder v3.17 DNAJC6 Sarah Leigh Classified gene: DNAJC6 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v3.17 DNAJC6 Sarah Leigh Gene: dnajc6 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.16 DNAJC6 Sarah Leigh Classified gene: DNAJC6 as Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v3.16 DNAJC6 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia, chorea or related movement disorder v3.16 DNAJC6 Sarah Leigh Gene: dnajc6 has been classified as Green List (High Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.12 TSPOAP1 Sarah Leigh changed review comment from: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. At least TSPOAP1 three variants have been reported in three unrelated families. Family members carrying homozygous TSPOAP1 variants have dystonia, intellectual disability and cerebellar atrophy to varying degrees. Motor symptoms were apparent between 11 and 13 years of age for NM_004758: c.2449_2450delinsTG, p.Gln817* and c.538delG, p.Ala180Profs*8, while NM_004758: c.5422G>A, p.Gly1808Ser was from 58 years through to the 60s. Similarly, cognitive impairment was apparent from school age and progressed to moderate to extensive, in the carries of the two terminating TSPOAP1 variants, while those with the missense variant were diagnosed with mild cognitive impairment (PMID: 33539324). In vitro functional studies and mouse models support the association of the TSPOAP1 variants and phenotypes seen in the cases (PMID: 33539324).; to: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. At least three TSPOAP1variants have been reported in three unrelated families. Family members carrying homozygous TSPOAP1 variants have dystonia, intellectual disability and cerebellar atrophy to varying degrees. Motor symptoms were apparent between 11 and 13 years of age for NM_004758: c.2449_2450delinsTG, p.Gln817* and c.538delG, p.Ala180Profs*8, while NM_004758: c.5422G>A, p.Gly1808Ser was from 58 years through to the 60s. Similarly, cognitive impairment was apparent from school age and progressed to moderate to extensive, in the carries of the two terminating TSPOAP1 variants, while those with the missense variant were diagnosed with mild cognitive impairment (PMID: 33539324). In vitro functional studies and mouse models support the association of the TSPOAP1 variants and phenotypes seen in the cases (PMID: 33539324).
Childhood onset dystonia, chorea or related movement disorder v3.12 TSPOAP1 Sarah Leigh changed review comment from: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. At least TSPOAP1 three variants have been reported in three unrelated families. Family members carrying homozygous TSPOAP1 variants have dystonia, intellectual disability and cerebellar atrophy to varying degrees (PMID: 33539324). In vitro functional studies and mouse models support the association of the TSPOAP1 variants and phenotypes seen in the cases (PMID: 33539324).; to: Not associated with a phenotype in OMIM, Gen2Phen or MONDO. At least TSPOAP1 three variants have been reported in three unrelated families. Family members carrying homozygous TSPOAP1 variants have dystonia, intellectual disability and cerebellar atrophy to varying degrees. Motor symptoms were apparent between 11 and 13 years of age for NM_004758: c.2449_2450delinsTG, p.Gln817* and c.538delG, p.Ala180Profs*8, while NM_004758: c.5422G>A, p.Gly1808Ser was from 58 years through to the 60s. Similarly, cognitive impairment was apparent from school age and progressed to moderate to extensive, in the carries of the two terminating TSPOAP1 variants, while those with the missense variant were diagnosed with mild cognitive impairment (PMID: 33539324). In vitro functional studies and mouse models support the association of the TSPOAP1 variants and phenotypes seen in the cases (PMID: 33539324).
Childhood onset dystonia, chorea or related movement disorder v3.12 TSPOAP1 Sarah Leigh Classified gene: TSPOAP1 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v3.12 TSPOAP1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia, chorea or related movement disorder v3.12 TSPOAP1 Sarah Leigh Gene: tspoap1 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.11 NUP54 Achchuthan Shanmugasundram changed review comment from: PMID:36333996 reported three unrelated patients with early-onset dystonia with striatal lesions identified with biallelic variants in NUP54 gene. One patient (patient A) had homozygous variant c.1073T>G (p.Ile358Ser), while other two patients had compound heterozygous variants (patient B: c.1073T>G (p.Ile358Ser) & c.1126A>G (p.Lys376Glu); patient C: c.1410_1412del (p.Gln471del) and two missense variants c.1414G>A (p.Glu472Lys) & c.1420C>T (p.Leu474Phe)).

The age of onset was between 12 months and five years and all had progressive neurological deterioration with dystonia, ataxia, dysarthria, dysphagia, hypotonia.

This gene has been associated with relevant phenotypes in Gene2Phenotype (NUP54-related early-onset dystonia with striatal lesions with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature; to: PMID:36333996 reported three unrelated patients with early-onset dystonia with striatal lesions identified with biallelic variants in NUP54 gene. One patient (patient A) had homozygous variant c.1073T>G (p.Ile358Ser), while other two patients had compound heterozygous variants (patient B: c.1073T>G (p.Ile358Ser) & c.1126A>G (p.Lys376Glu); patient C: c.1410_1412del (p.Gln471del) and two missense variants c.1414G>A (p.Glu472Lys) & c.1420C>T (p.Leu474Phe)).

The age of onset was between 12 months and five years and all had progressive neurological deterioration with dystonia, ataxia, dysarthria, dysphagia, hypotonia.

Western blots showed reduced expression of NUP54 and its interaction partners NUP62/NUP58 in patient fibroblasts.

This gene has been associated with relevant phenotypes in Gene2Phenotype (NUP54-related early-onset dystonia with striatal lesions with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature
Childhood onset dystonia, chorea or related movement disorder v3.11 NUP54 Achchuthan Shanmugasundram Classified gene: NUP54 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v3.11 NUP54 Achchuthan Shanmugasundram Added comment: Comment on list classification: There is sufficient evidence (3 unrelated cases) for rating this gene as GREEN in the next GMS review.
Childhood onset dystonia, chorea or related movement disorder v3.11 NUP54 Achchuthan Shanmugasundram Gene: nup54 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.10 NUP54 Achchuthan Shanmugasundram gene: NUP54 was added
gene: NUP54 was added to Childhood onset dystonia, chorea or related movement disorder. Sources: Literature
Mode of inheritance for gene: NUP54 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: NUP54 were set to 36333996
Phenotypes for gene: NUP54 were set to Early-onset dystonia
Review for gene: NUP54 was set to GREEN
Added comment: PMID:36333996 reported three unrelated patients with early-onset dystonia with striatal lesions identified with biallelic variants in NUP54 gene. One patient (patient A) had homozygous variant c.1073T>G (p.Ile358Ser), while other two patients had compound heterozygous variants (patient B: c.1073T>G (p.Ile358Ser) & c.1126A>G (p.Lys376Glu); patient C: c.1410_1412del (p.Gln471del) and two missense variants c.1414G>A (p.Glu472Lys) & c.1420C>T (p.Leu474Phe)).

The age of onset was between 12 months and five years and all had progressive neurological deterioration with dystonia, ataxia, dysarthria, dysphagia, hypotonia.

This gene has been associated with relevant phenotypes in Gene2Phenotype (NUP54-related early-onset dystonia with striatal lesions with 'moderate' rating in the DD panel), but not in OMIM.
Sources: Literature
Childhood onset dystonia, chorea or related movement disorder v3.8 ARFGEF3 Achchuthan Shanmugasundram Classified gene: ARFGEF3 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v3.8 ARFGEF3 Achchuthan Shanmugasundram Added comment: Comment on list classification: As reviewed by Zornitza Stark, there are three unrelated cases with monoallelic variants in this gene and with childhood-onset dystonia. Hence, this gene can be promoted to GREEN at the next major update.
Childhood onset dystonia, chorea or related movement disorder v3.8 ARFGEF3 Achchuthan Shanmugasundram Gene: arfgef3 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v3.2 SPG7 Sarah Leigh Phenotypes for gene: SPG7 were changed from Spastic paraplegia 7, 607259 to Spastic paraplegia 7, autosomal recessive, OMIM:607259; hereditary spastic paraplegia 7, MONDO:0011803
Childhood onset dystonia, chorea or related movement disorder v3.1 Catherine Snow Panel version 3.0 has been signed off on 2023-03-22
Childhood onset dystonia, chorea or related movement disorder v3.0 Catherine Snow promoted panel to version 3.0
Childhood onset dystonia, chorea or related movement disorder v2.11 CACNB4 Eleanor Williams changed review comment from: The mode of inheritance of this gene has been updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.; to: The mode of inheritance of this gene was proposed to be changed to Both mono and biallelic in 2022 but since there is no new evidence since it was last considered by the GMS, it has been decided to keep it as just monoallelic.
Childhood onset dystonia, chorea or related movement disorder v2.9 FXN_GAA Eleanor Williams Classified STR: FXN_GAA as Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v2.9 FXN_GAA Eleanor Williams Str: fxn_gaa has been classified as Green List (High Evidence).
Childhood onset dystonia, chorea or related movement disorder v2.1 Arina Puzriakova Panel version 2.0 has been signed off on 2022-11-30
Childhood onset dystonia, chorea or related movement disorder v2.0 Arina Puzriakova promoted panel to version 2.0
Childhood onset dystonia, chorea or related movement disorder v1.263 ADAR Arina Puzriakova Added comment: Comment on mode of inheritance: Should be updated from biallelic only to both mono- and biallelic at the next GMS panel update.

Dystonia is an established feature of AGS6 (MIM# 615010) associated with AR variants in this gene. Overall the AD condition (dyschromatosis symmetrica hereditaria, MIM# 127400) often presents with changes in skin pigmentation as the only sign of disease. However, there have also been reports of neurologic deficits including ID, developmental regression, brain calcification, seizures and dystonia in some affected individuals, particularly with the Gly1007Arg variant (PMID: 16225627; 16817193; 19017046). Although the penetrance of extracutaneous features is reduced, there is value in testing heterozygous ADAR variants on these panels to ensure syndromic cases are not missed if not tested in the context of the skin phenotype.
Childhood onset dystonia, chorea or related movement disorder v1.262 ADAR Arina Puzriakova Phenotypes for gene: ADAR were changed from Aicardi-Goutieres syndrome 6, 615010; dystonia to Aicardi-Goutieres syndrome 6, OMIM:615010; Dyschromatosis symmetrica hereditaria, OMIM:127400
Childhood onset dystonia, chorea or related movement disorder v1.261 AP1S2 Arina Puzriakova changed review comment from: Comment on mode of inheritance: Review of literature did not reveal any confirmed affected females. Female carriers of AP1S2 variants are phenotypically normal and have mostly shown random X-inactivation. Huo et al., 2019 (PMID: 30714330) state that they identified a female patient (I-1) but this individual was not available for genetic testing and so it is unclear whether they harboured a variant on a one or both alleles.

As no confirmed female cases have been reported and the allelic requirement remains elusive, the MOI should be set to the default XL (i.e. monoallelic in females may cause disease) as this will ensure that both mono and biallelic variants are picked up in females by the pipeline.; to: Comment on mode of inheritance: Review of literature did not reveal any confirmed affected females. Female carriers of AP1S2 variants are phenotypically normal and have mostly shown random X-inactivation. Huo et al., 2019 (PMID: 30714330) state that they identified a female patient (I-1) but this individual was not available for genetic testing and so it is unclear whether they harboured a variant on a one or both alleles.

As it is not known definitively whether females require a variant on each allele of this gene in order to be affected, the MOI should be set to the default XL (i.e. monoallelic in females may cause disease).
Childhood onset dystonia, chorea or related movement disorder v1.261 STUB1 Sarah Leigh Added comment: Comment on mode of inheritance: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Numerous STUB1 variants have been reported in both Autosomal recessive spinocerebellar ataxia type 16, OMIM:615768 and Spinocerebellar ataxia 48, OMIM:618093. PMIDs 34906452; 35493319 report digenic occurrence of heterozygous STUB1 variants, with TBP_CAG expansions of 41-46. They question the validy of Spinocerebellar ataxia 48 (OMIM:618093) as a condition and whether it should be included into Spinocerebellar ataxia 17 (OMIM:607136).
Childhood onset dystonia, chorea or related movement disorder v1.260 STUB1 Sarah Leigh Phenotypes for gene: STUB1 were changed from Spinocerebellar ataxia, autosomal recessive 16, 615768 to Autosomal recessive spinocerebellar ataxia type 16, OMIM:615768; autosomal recessive spinocerebellar ataxia 16, MONDO:0014339; Spinocerebellar ataxia 48, OMIM:618093; spinocerebellar ataxia 48, MONDO:0032526
Childhood onset dystonia, chorea or related movement disorder v1.258 XK Sarah Leigh Classified gene: XK as Red List (low evidence)
Childhood onset dystonia, chorea or related movement disorder v1.258 XK Sarah Leigh Added comment: Comment on list classification: Not appropriate for this panel, as older onset.
Childhood onset dystonia, chorea or related movement disorder v1.258 XK Sarah Leigh Gene: xk has been classified as Red List (Low Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.257 XK Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Numerous variants have been reported in cases of McLeod syndrome with or without chronic granulomatous disease (OMIM:300842), including at least two cases in females; severe symptoms were apparent in the index case (11.1) who had marked skewed X-inactivation favouring the wild type allele (PMID: 8619554).
After consultation with Helen Brittain (Clinical Fellow, Genomics England) it has been concluded that it is not appropriate for XK to be green on the Childhood onset dystonia or chorea or related movement disorder panel, as the phenotype is not evident in childhood, but rather from the 4th decade of life (PMIDs: 11761473;8004674;11032622;11261514;33652783;30128557), therefore, variants in XK would be predictive of possible future conditions.; to: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Numerous variants have been reported in cases of McLeod syndrome with or without chronic granulomatous disease (OMIM:300842), including at least two cases in females; severe symptoms were apparent in the index case (11.1) who had marked skewed X-inactivation favouring the wild type allele (PMID: 8619554).
After consultation with Helen Brittain (Clinical Fellow, Genomics England) it has been concluded that it is not appropriate for XK to be green on the Childhood onset dystonia or chorea or related movement disorder panel, as the phenotype is not evident in childhood, but rather from the 4th decade of life (PMIDs: 11761473;8004674;11032622;11261514;33652783;30128557), therefore, variants in XK could be predictive of possible future conditions.
Childhood onset dystonia, chorea or related movement disorder v1.257 XK Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Numerous variants have been reported in cases of McLeod syndrome with or without chronic granulomatous disease (OMIM:300842), including at least two cases in females; severe symptoms were apparent in the index case (11.1) who had marked skewed X-inactivation favouring the wild type allele (PMID: 8619554).; to: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. Numerous variants have been reported in cases of McLeod syndrome with or without chronic granulomatous disease (OMIM:300842), including at least two cases in females; severe symptoms were apparent in the index case (11.1) who had marked skewed X-inactivation favouring the wild type allele (PMID: 8619554).
After consultation with Helen Brittain (Clinical Fellow, Genomics England) it has been concluded that it is not appropriate for XK to be green on the Childhood onset dystonia or chorea or related movement disorder panel, as the phenotype is not evident in childhood, but rather from the 4th decade of life (PMIDs: 11761473;8004674;11032622;11261514;33652783;30128557), therefore, variants in XK would be predictive of possible future conditions.
Childhood onset dystonia, chorea or related movement disorder v1.253 CLPB Arina Puzriakova Phenotypes for gene: CLPB were changed from 3-methylglutaconic aciduria, type VII, with cataracts, neurologic involvement and neutropenia, OMIM:616271 to 3-methylglutaconic aciduria, type VIIB, autosomal recessive, OMIM:616271; 3-methylglutaconic aciduria, type VIIA, autosomal dominant, OMIM:619835; Neutropenia, severe congenital, 9, autosomal dominant, OMIM:619813
Childhood onset dystonia, chorea or related movement disorder v1.249 NDUFA12 Arina Puzriakova Classified gene: NDUFA12 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.249 NDUFA12 Arina Puzriakova Gene: ndufa12 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.248 ATP5G3 Arina Puzriakova Classified gene: ATP5G3 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.248 ATP5G3 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Zornitza Stark (Australian Genomics). There is sufficient evidence to rate this gene as Green at the next GMS panel update - at least four unrelated families with heterozygous variants primarily presenting with dystonia or related movement disorder (PMID: 34636445; 34954817); also supportive Drosophila model described.
Childhood onset dystonia, chorea or related movement disorder v1.248 ATP5G3 Arina Puzriakova Gene: atp5g3 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.246 XK Sarah Leigh Classified gene: XK as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.246 XK Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia, chorea or related movement disorder v1.246 XK Sarah Leigh Gene: xk has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.245 XK Sarah Leigh Classified gene: XK as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.245 XK Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia, chorea or related movement disorder v1.245 XK Sarah Leigh Gene: xk has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.241 XK Sarah Leigh Phenotypes for gene: XK were changed from McLeod syndrome with or without chronic granulomatous disease MIM#300842 to McLeod syndrome with or without chronic granulomatous disease, OMIM:300842; McLeod neuroacanthocytosis syndrome, MONDO:0018945
Childhood onset dystonia, chorea or related movement disorder v1.240 HECW2 Arina Puzriakova Classified gene: HECW2 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.240 HECW2 Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to promote this gene to Green at the next GMS panel update. Motor dysfunction is a key feature in majority of cases and of all individuals aged 5 years or older, only 7/12 could walk, although often with limited capacity. Therefore, inclusion of HECW2 on this panel could present potential diagnostic benefit.
Childhood onset dystonia, chorea or related movement disorder v1.240 HECW2 Arina Puzriakova Gene: hecw2 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.238 MAL Sarah Leigh Classified gene: MAL as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.238 MAL Sarah Leigh Gene: mal has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.237 MAL Julia Baptista gene: MAL was added
gene: MAL was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Literature
Mode of inheritance for gene: MAL was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MAL were set to 35217805
Phenotypes for gene: MAL were set to developmental delay; nystagmus; progressive motor deterioration; dysmyelination
Review for gene: MAL was set to AMBER
Added comment: Single consanguineous family reported with two affected children (DD and nystagmus). New onset ataxia and cerebellar volume loss with patchy dysmyelination. Homozygous missense variant identified by exome analysis segregated with the condition. Functional data suggested that p.(Ala109Asp) severely affects protein folding of MAL, leading to mislocalization in the ER.
Sources: Literature
Childhood onset dystonia, chorea or related movement disorder v1.237 CACNB4 Sarah Leigh commented on gene: CACNB4: NHSGenomic Medicine Service consideration - limited evidence for biallelic mode of inheritance.
Childhood onset dystonia, chorea or related movement disorder v1.237 CACNB4 Sarah Leigh commented on gene: CACNB4: After NHSGenomic Medicine Service consideration, the mode of inheritance of this gene has not been changed
Childhood onset dystonia, chorea or related movement disorder v1.233 SNORD118 Sarah Leigh Classified gene: SNORD118 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.233 SNORD118 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia, chorea or related movement disorder v1.233 SNORD118 Sarah Leigh Gene: snord118 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.232 AFG3L2 Arina Puzriakova Phenotypes for gene: AFG3L2 were changed from Spinocerebellar ataxia 28, OMIM:610246; Spastic ataxia 5, autosomal recessive, OMIM:614487Optic atrophy 12, OMIM:618977; Spinocerebellar ataxia 28, OMIM:610246; Spastic ataxia 5, autosomal recessive, OMIM:614487 to Spastic ataxia 5, autosomal recessive, OMIM:614487
Childhood onset dystonia, chorea or related movement disorder v1.231 AFG3L2 Arina Puzriakova Phenotypes for gene: AFG3L2 were changed from Spastic ataxia 5, autosomal recessive 614487; Spinocerebellar ataxia 28 610246 to Spinocerebellar ataxia 28, OMIM:610246; Spastic ataxia 5, autosomal recessive, OMIM:614487Optic atrophy 12, OMIM:618977; Spinocerebellar ataxia 28, OMIM:610246; Spastic ataxia 5, autosomal recessive, OMIM:614487
Childhood onset dystonia, chorea or related movement disorder v1.228 HSPD1 Arina Puzriakova Added comment: Comment on mode of inheritance: Should be updated from 'both mono- and biallelic' to 'biallelic' only at the next GMS panel update. Biallelic variants cause a paediatric-onset leukodystrophy (MIM# 612233) which features motor disability associated progressive limb spasticity and contractures, and some patients have been found to have choreoatetotic movements (PMID: 18571143, 27405012). On the other hand, monoallelic variants are associated with a pure adult-onset HSP (SPG13, MIM# 605280) which is not pertinent to this panel.
Childhood onset dystonia, chorea or related movement disorder v1.227 C19orf12 Sarah Leigh Phenotypes for gene: C19orf12 were changed from neurodegeneration with brain iron accumulation-4, 614298; mitochondrial membrane protein-associated neurodegeneration; Dystonia to ?Spastic paraplegia 43, autosomal recessive, OMIM:615043; Neurodegeneration with brain iron accumulation 4, OMIM: 614298
Childhood onset dystonia, chorea or related movement disorder v1.224 PNPT1 Arina Puzriakova Classified gene: PNPT1 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.224 PNPT1 Arina Puzriakova Added comment: Comment on list classification: Upgraded from Red to Amber but there are sufficient unrelated cases to rate this gene as Green at the next GMS review.
Childhood onset dystonia, chorea or related movement disorder v1.224 PNPT1 Arina Puzriakova Gene: pnpt1 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.221 ZNF423 Arina Puzriakova Phenotypes for gene: ZNF423 were changed from Joubert syndrome 19; Nephronophthisis 14; Nephronophthisis 14, 614844; Joubert syndrome 19, 614844; Joubert syndrome with oculorenal defect to Joubert syndrome 19, OMIM:614844; Nephronophthisis 14, OMIM:614844
Childhood onset dystonia, chorea or related movement disorder v1.220 TOR1A Arina Puzriakova Phenotypes for gene: TOR1A were changed from Dystonia-1, torsion, OMIM:128100; Dystonic disorder, MONDO:0003441 to Dystonia-1, torsion, OMIM:128100; Arthrogryposis multiplex congenita 5, OMIM:618947
Childhood onset dystonia, chorea or related movement disorder v1.218 TOR1A Arina Puzriakova reviewed gene: TOR1A: Rating: ; Mode of pathogenicity: None; Publications: ; Phenotypes: Dystonia-1, torsion, OMIM:128100, Arthrogryposis multiplex congenita 5, OMIM:618947; Mode of inheritance: None
Childhood onset dystonia, chorea or related movement disorder v1.218 ACER3 Arina Puzriakova gene: ACER3 was added
gene: ACER3 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Expert Review Amber,Literature
Q1_22_rating tags were added to gene: ACER3.
Mode of inheritance for gene: ACER3 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: ACER3 were set to 26792856; 32816236; 34281620
Phenotypes for gene: ACER3 were set to Leukodystrophy, progressive, early childhood-onset, OMIM:617762
Childhood onset dystonia, chorea or related movement disorder v1.210 ATP5G3 Zornitza Stark gene: ATP5G3 was added
gene: ATP5G3 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Literature
Mode of inheritance for gene: ATP5G3 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: ATP5G3 were set to 34636445; 34954817
Phenotypes for gene: ATP5G3 were set to Dystonia, early-onset, and/or spastic paraplegia, MIM# 619681
Review for gene: ATP5G3 was set to GREEN
Added comment: Note that HGNC approved gene name is ATP5MC3.

PMID: 34636445 reports a missense variant identified in a large single-family pedigree with dystonia and spastic paraplegia. The variant was identified via exome sequencing of the proband and a distant cousin, focussing on variants within the previously determined linkage region. The identical missense variant was also identified in a patient with childhood onset dystonic syndrome and was shown to be de novo. Functional studies of fibroblast cell lines from affected father (HSP) and proband of large family demonstrated decreased complex V function. A drosophila model containing the missense variant had reduced mobility and reduced complex V activity.

PMID: 34954817 reports de novo monoallelic missense variants in three individuals, however one of these individuals was reported in above paper. The other two patients were: (1) a-15-year-old girl with milestone delay, pyramidal signs, and generalized dystonia with prominent upper-body involvement, and (2) a 6-year-old boy with delayed psychomotor development, lower-extremity spasticity, and elevated blood lactate levels
Sources: Literature
Childhood onset dystonia, chorea or related movement disorder v1.209 TARS2 Sarah Leigh Classified gene: TARS2 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.209 TARS2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia, chorea or related movement disorder v1.209 TARS2 Sarah Leigh Gene: tars2 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.208 TARS2 Sarah Leigh Classified gene: TARS2 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.208 TARS2 Sarah Leigh Gene: tars2 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.207 TARS2 Sarah Leigh changed review comment from: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 11 variants reported in at least 7 unrelated cases with a varied phenotype, including encephalomyopathy, epilepsy, dystonia, hyperhidrosis and severe hearing impairment. Supportive functional studies were also presented PMID: 34508595.; to: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen. At least 11 variants reported in at least 7 unrelated cases with a varied phenotype, including encephalomyopathy, epilepsy, dystonia, hyperhidrosis and severe hearing impairment. At least three unrelated cases of dystonia reported. Supportive functional studies were also presented PMID: 34508595.
Childhood onset dystonia, chorea or related movement disorder v1.205 SLC30A10 Arina Puzriakova Phenotypes for gene: SLC30A10 were changed from Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, and Chronic Liver Disease; Hypermanganesemia with dystonia, polycythemia, and cirrhosis, 613280 to Hypermanganesemia with dystonia 1, OMIM:613280
Childhood onset dystonia, chorea or related movement disorder v1.202 EXOSC3 Arina Puzriakova Phenotypes for gene: EXOSC3 were changed from to Pontocerebellar hypoplasia, type 1B, OMIM:614678
Childhood onset dystonia, chorea or related movement disorder v1.198 CLPB Arina Puzriakova Added comment: Comment on mode of inheritance: MOI should be updated from 'Biallelic' to 'Both mono- and biallelic' at the next GMS update.

Association between biallelic variants and disease is well established, with at least 7 affected individuals reported with a movement disorder. Recently, Wortmann et al. 2021 (PMID: 34140661) published six unrelated individuals with one of four different de novo monoallelic missense variants in CLPB. The phenotype strongly overlapped with that observed in the recessive disease. Three individuals were nonambulatory and one was ambulatory but with a wide based gait and not able to run or jump. Some functional studies of heterozygous variants were performed.
Childhood onset dystonia, chorea or related movement disorder v1.196 FXN Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: FXN.
Childhood onset dystonia, chorea or related movement disorder v1.196 NOP56 Arina Puzriakova Classified gene: NOP56 as Red List (low evidence)
Childhood onset dystonia, chorea or related movement disorder v1.196 NOP56 Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red, this review is for the STR entity and not the gene entity
Childhood onset dystonia, chorea or related movement disorder v1.196 NOP56 Arina Puzriakova Gene: nop56 has been classified as Red List (Low Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.195 NOP56 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Childhood onset dystonia, chorea or related movement disorder v1.193 NOP56 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: NOP56.
Tag currently-ngs-unreportable tag was added to gene: NOP56.
Childhood onset dystonia, chorea or related movement disorder v1.192 PPP2R2B Arina Puzriakova Classified gene: PPP2R2B as Red List (low evidence)
Childhood onset dystonia, chorea or related movement disorder v1.192 PPP2R2B Arina Puzriakova Added comment: Comment on list classification: Demoted from Amber to Red, this review is for the STR entity and not the gene entity
Childhood onset dystonia, chorea or related movement disorder v1.192 PPP2R2B Arina Puzriakova Gene: ppp2r2b has been classified as Red List (Low Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.191 PPP2R2B Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Childhood onset dystonia, chorea or related movement disorder v1.190 PPP2R2B Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: PPP2R2B.
Tag currently-ngs-unreportable tag was added to gene: PPP2R2B.
Childhood onset dystonia, chorea or related movement disorder v1.187 HTT Arina Puzriakova Classified gene: HTT as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.187 HTT Arina Puzriakova Gene: htt has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.183 DMPK Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Childhood onset dystonia, chorea or related movement disorder v1.182 CSTB Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: CSTB.
Childhood onset dystonia, chorea or related movement disorder v1.182 CSTB Arina Puzriakova reviewed gene: CSTB: Rating: ; Mode of pathogenicity: None; Publications: 26843564; Phenotypes: Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) OMIM:254800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v1.182 CSTB_CCCCGCCCCGCG Arina Puzriakova Phenotypes for STR: CSTB_CCCCGCCCCGCG were changed from Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), OMIM:254800
Childhood onset dystonia, chorea or related movement disorder v1.180 C9orf72_GGGGCC Arina Puzriakova Phenotypes for STR: C9orf72_GGGGCC were changed from Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 OMIM:105550; frontotemporal dementia and/or amyotrophic lateral sclerosis 1 MONDO:0007105 to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550
Childhood onset dystonia, chorea or related movement disorder v1.179 C9orf72 Arina Puzriakova Phenotypes for gene: C9orf72 were changed from Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 OMIM:105550; frontotemporal dementia and/or amyotrophic lateral sclerosis 1 MONDO:0007105 to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, OMIM:105550
Childhood onset dystonia, chorea or related movement disorder v1.177 ATXN1 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN1.
Tag currently-ngs-unreportable tag was added to gene: ATXN1.
Childhood onset dystonia, chorea or related movement disorder v1.177 ATXN1 Arina Puzriakova Classified gene: ATXN1 as Red List (low evidence)
Childhood onset dystonia, chorea or related movement disorder v1.177 ATXN1 Arina Puzriakova Gene: atxn1 has been classified as Red List (Low Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.176 ATXN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Childhood onset dystonia, chorea or related movement disorder v1.175 ATXN7 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Childhood onset dystonia, chorea or related movement disorder v1.174 ATXN7 Arina Puzriakova Classified gene: ATXN7 as Red List (low evidence)
Childhood onset dystonia, chorea or related movement disorder v1.174 ATXN7 Arina Puzriakova Gene: atxn7 has been classified as Red List (Low Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.173 ATXN7 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN7.
Tag currently-ngs-unreportable tag was added to gene: ATXN7.
Childhood onset dystonia, chorea or related movement disorder v1.173 ATXN2_CAG Arina Puzriakova Phenotypes for STR: ATXN2_CAG were changed from Spinocerebellar ataxia 2, 183090 to Spinocerebellar ataxia 2, OMIM:183090; {Amyotrophic lateral sclerosis, susceptibility to, 13}, OMIM:183090
Childhood onset dystonia, chorea or related movement disorder v1.171 ATXN10 Arina Puzriakova Classified gene: ATXN10 as Red List (low evidence)
Childhood onset dystonia, chorea or related movement disorder v1.171 ATXN10 Arina Puzriakova Gene: atxn10 has been classified as Red List (Low Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.170 ATXN10 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATXN10.
Tag currently-ngs-unreportable tag was added to gene: ATXN10.
Childhood onset dystonia, chorea or related movement disorder v1.170 ATXN10 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Childhood onset dystonia, chorea or related movement disorder v1.168 ATN1 Arina Puzriakova Added comment: Comment on mode of inheritance: Lack of phenotypic relevance for SNVs - nucleotide repeat expansion mechanism
Childhood onset dystonia, chorea or related movement disorder v1.167 ATN1 Arina Puzriakova Phenotypes for gene: ATN1 were changed from Dentatorubro-pallidoluysian atrophy, 125370 to Dentatorubral-pallidoluysian atrophy, OMIM:125370
Childhood onset dystonia, chorea or related movement disorder v1.166 ATN1 Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: ATN1.
Tag currently-ngs-unreportable tag was added to gene: ATN1.
Childhood onset dystonia, chorea or related movement disorder v1.166 DHDDS Arina Puzriakova Classified gene: DHDDS as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.166 DHDDS Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Childhood onset dystonia, chorea or related movement disorder v1.166 DHDDS Arina Puzriakova Gene: dhdds has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.159 AP1S2 Arina Puzriakova Added comment: Comment on mode of inheritance: Review of literature did not reveal any confirmed affected females. Female carriers of AP1S2 variants are phenotypically normal and have mostly shown random X-inactivation. Huo et al., 2019 (PMID: 30714330) state that they identified a female patient (I-1) but this individual was not available for genetic testing and so it is unclear whether they harboured a variant on a one or both alleles.

As no confirmed female cases have been reported and the allelic requirement remains elusive, the MOI should be set to the default XL (i.e. monoallelic in females may cause disease) as this will ensure that both mono and biallelic variants are picked up in females by the pipeline.
Childhood onset dystonia, chorea or related movement disorder v1.155 IMPDH2 Arina Puzriakova Classified gene: IMPDH2 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.155 IMPDH2 Arina Puzriakova Added comment: Comment on list classification: This gene is not yet associated with a relevant phenotype in OMIM or G2P, but there are sufficient unrelated cases (3) presenting with signs of dystonia to rate as Green at the next GMS review. Other cases reported with motor dysfunction, and it is plausible that this may develop into dystonia later in life.
Childhood onset dystonia, chorea or related movement disorder v1.155 IMPDH2 Arina Puzriakova Gene: impdh2 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.154 IMPDH2 Arina Puzriakova edited their review of gene: IMPDH2: Added comment: Kuukasjärvi et al., 2021 (PMID: 34305140) report on an additional large Finnish family (6 affected members) with a heterozygous truncating variant co-segregating with a dominantly inherited dystonia-tremor phenotype. Patient fibroblasts showed reduced IMPDH2 expression. IMPDH2 is the rate-limiting enzyme in the biosynthesis of guanine nucleotides, a dopamine synthetic pathway previously linked to childhood or adolescence-onset dystonia disorders.; Changed publications to: 33098801, 34305140
Childhood onset dystonia, chorea or related movement disorder v1.151 GRIN1 Sarah Leigh edited their review of gene: GRIN1: Added comment: Associated with relevant phenotype in OMIM, but not associated with phenotype in Gen2Phen, although there is a confirmed association with epileptic encephalopathy in Gen2Phen. At least 20 variants have been associated with Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant OMIM:614254 and three have been associated with Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive OMIM:617820.; Changed rating: GREEN
Childhood onset dystonia, chorea or related movement disorder v1.150 GRIN1 Sarah Leigh Classified gene: GRIN1 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.150 GRIN1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia, chorea or related movement disorder v1.150 GRIN1 Sarah Leigh Gene: grin1 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.149 GRIN1 Sarah Leigh Phenotypes for gene: GRIN1 were changed from Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, MIM# 614254; Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive, MIM# 617820 to Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant OMIM:614254; intellectual disability, autosomal dominant 8 MONDO:0013655; Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive OMIM:617820; neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive MONDO:0060629
Childhood onset dystonia, chorea or related movement disorder v1.147 GNB1 Sarah Leigh Classified gene: GNB1 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.147 GNB1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia, chorea or related movement disorder v1.147 GNB1 Sarah Leigh Gene: gnb1 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.146 SLC16A2 Arina Puzriakova Classified gene: SLC16A2 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.146 SLC16A2 Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green at the next GMS panel update.
Childhood onset dystonia, chorea or related movement disorder v1.146 SLC16A2 Arina Puzriakova Gene: slc16a2 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.142 SERAC1 Arina Puzriakova Phenotypes for gene: SERAC1 were changed from Lesions in the basal ganglia; MEGDEL syndrome; MEGDHEL syndrome; Dystonia; 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, 614739; 3-MEthylGlutaconic aciduria, Dystonia-Deafness, Hepatopathy, Encephalopathy, Leigh-like syndrome to 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, OMIM:614739
Childhood onset dystonia, chorea or related movement disorder v1.141 KIF1C Arina Puzriakova Phenotypes for gene: KIF1C were changed from Spastic ataxia 2, autosomal recessive, 611302 to Spastic ataxia 2, autosomal recessive, OMIM:611302
Childhood onset dystonia, chorea or related movement disorder v1.139 KIF1A Arina Puzriakova Classified gene: KIF1A as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.139 KIF1A Arina Puzriakova Added comment: Comment on list classification: Dystonia can be feature of NESCAV syndrome (MIM# 614255) caused by heterozygous variants in this gene. However, KIF1A is associated with multiple phenotypes that do not include dystonia, and even NESCAV syndrome is more likely to be investigated in the context of other more prominent features such as spasticity and intellectual disability, for which this gene is already Green. For this reason, classifying as Amber on this panel.
Childhood onset dystonia, chorea or related movement disorder v1.139 KIF1A Arina Puzriakova Gene: kif1a has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.138 Ivone Leong List of related panels changed from R57 to R57; Childhood onset dystonia; chorea or related movement disorder
Panel version 1.137 has been signed off on 2021-08-05
Childhood onset dystonia, chorea or related movement disorder v1.137 C9orf72_GGGGCC Sarah Leigh Classified STR: C9orf72_GGGGCC as Red List (low evidence)
Childhood onset dystonia, chorea or related movement disorder v1.137 C9orf72_GGGGCC Sarah Leigh Added comment: Comment on list classification: Reviews for C9orf72 gene on this panel from Zornitza Stark (Australian Genomics), James Polke (North Thames GLH) & Helen Brittain (Genomics England Clinical Fellow)(https://panelapp.genomicsengland.co.uk/panels/847/gene/C9orf72/#!review), together recommend a Red rating, as the phenotype associated with this variant in this gene has an adult onset and is therefore not appropriate for a childhood gene panel.
Childhood onset dystonia, chorea or related movement disorder v1.137 C9orf72_GGGGCC Sarah Leigh Str: c9orf72_ggggcc has been classified as Red List (Low Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.136 DMPK Arina Puzriakova changed review comment from: Comment on list classification: Demoted from Green to Red due to the disease-causing mechanism - genetic defect is an amplified trinucleotide CTG repeat in the 3'UTR (currently NGS unreportable), rather than SNVs within the gene. Evidence level for this is high - it is a confirmed DD gene for DYSTROPHIA MYOTONICA TYPE 1.; to: Comment on list classification: Demoted from Amber to Red due to the disease-causing mechanism - genetic defect is an amplified trinucleotide CTG repeat in the 3'UTR (currently NGS unreportable), rather than SNVs within the gene. Evidence level for this is high - it is a confirmed DD gene for DYSTROPHIA MYOTONICA TYPE 1.
Childhood onset dystonia, chorea or related movement disorder v1.136 DMPK Arina Puzriakova Tag nucleotide-repeat-expansion tag was added to gene: DMPK.
Tag currently-ngs-unreportable tag was added to gene: DMPK.
Childhood onset dystonia, chorea or related movement disorder v1.135 DMPK Arina Puzriakova Classified gene: DMPK as Red List (low evidence)
Childhood onset dystonia, chorea or related movement disorder v1.135 DMPK Arina Puzriakova Added comment: Comment on list classification: Demoted from Green to Red due to the disease-causing mechanism - genetic defect is an amplified trinucleotide CTG repeat in the 3'UTR (currently NGS unreportable), rather than SNVs within the gene. Evidence level for this is high - it is a confirmed DD gene for DYSTROPHIA MYOTONICA TYPE 1.
Childhood onset dystonia, chorea or related movement disorder v1.135 DMPK Arina Puzriakova Gene: dmpk has been classified as Red List (Low Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.134 ATM Arina Puzriakova Phenotypes for gene: ATM were changed from Dystonia; Ataxia telangiectasia, 208900 to Ataxia-telangiectasia, OMIM:208900
Childhood onset dystonia, chorea or related movement disorder v1.132 DMPK Dmitrijs Rots changed review comment from: Causes myotinic dystonia only due to STR expansion, not SNVs.; to: Causes myotinic dystrophy only due to STR expansion, not SNVs.
Childhood onset dystonia, chorea or related movement disorder v1.131 SCN8A Arina Puzriakova Phenotypes for gene: SCN8A were changed from paroxysmal kinesigenic dyskinesias; epilepsy, Seizures, benign familial infantile, 5, 617080 to Seizures, benign familial infantile, 5, OMIM:617080; Paroxysmal kinesigenic dyskinesias
Childhood onset dystonia, chorea or related movement disorder v1.128 VPS41 Arina Puzriakova Classified gene: VPS41 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.128 VPS41 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). There is sufficient evidence to promote this gene to Green at the next GSM panel update.
Childhood onset dystonia, chorea or related movement disorder v1.128 VPS41 Arina Puzriakova Gene: vps41 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.126 VPS16 Arina Puzriakova Classified gene: VPS16 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.126 VPS16 Arina Puzriakova Added comment: Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). There is sufficient evidence to promote this gene to Green at the next GMS panel update - at least 19 unrelated families reported with progressive dystonia (both multifocal and generalised types described) in association with variants in this gene (publications updated with relevant literature). Variable age of onset ranging from 3 to 50 years.
Childhood onset dystonia, chorea or related movement disorder v1.126 VPS16 Arina Puzriakova Gene: vps16 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.125 VPS16 Arina Puzriakova Added comment: Comment on mode of inheritance: While most cases of VPS16-related dystonia have been due to heterozygous variants, one Chinese consanguineous family with dystonia has been found to harbour a homozygous missense variant (PMID:27174565). In view of only one biallelic case, MOI has been set as 'Monoallelic' - patients with biallelic variants would still be picked up by the Genomics England pipeline.

Furthermore, biallelic VPS16 variants have been linked to a mucopolysaccharidosis‐like disease - reviewed on the 'Lysosomal storage disorder' (R276) panel.
Childhood onset dystonia, chorea or related movement disorder v1.122 FOXG1 Sarah Leigh edited their review of gene: FOXG1: Added comment: Associated with relevant phenotype in OMIM and as confirmed Gen2Phen gene. All of the patients with FOXG1 variants reported in PMID 27029630 abnormal involuntary movements, including chorea/athetosis in 22/25 (88%) cases.; Changed rating: GREEN
Childhood onset dystonia, chorea or related movement disorder v1.121 FOXG1 Sarah Leigh Classified gene: FOXG1 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.121 FOXG1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia, chorea or related movement disorder v1.121 FOXG1 Sarah Leigh Gene: foxg1 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.118 FUCA1 Sarah Leigh Classified gene: FUCA1 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.118 FUCA1 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia, chorea or related movement disorder v1.118 FUCA1 Sarah Leigh Gene: fuca1 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.117 FUCA1 Sarah Leigh Phenotypes for gene: FUCA1 were changed from to Fucosidosis OMIM:230000; fucosidosis MONDO:0009254
Childhood onset dystonia, chorea or related movement disorder v1.110 C9orf72_GGGGCC Sarah Leigh Phenotypes for STR: C9orf72_GGGGCC were changed from Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 105550 to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 OMIM:105550; frontotemporal dementia and/or amyotrophic lateral sclerosis 1 MONDO:0007105
Childhood onset dystonia, chorea or related movement disorder v1.109 C9orf72 Sarah Leigh Phenotypes for gene: C9orf72 were changed from Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 105550 to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 OMIM:105550; frontotemporal dementia and/or amyotrophic lateral sclerosis 1 MONDO:0007105
Childhood onset dystonia, chorea or related movement disorder v1.107 C9orf72_GGGGCC Sarah Leigh Classified STR: C9orf72_GGGGCC as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.107 C9orf72_GGGGCC Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia, chorea or related movement disorder v1.107 C9orf72_GGGGCC Sarah Leigh Str: c9orf72_ggggcc has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.106 C9orf72_GGGGCC Sarah Leigh STR: C9orf72_GGGGCC was added
STR: C9orf72_GGGGCC was added to Childhood onset dystonia or chorea or related movement disorder. Sources: NHS GMS,Expert Review Green,London North GLH,Expert list
STR tags were added to STR: C9orf72_GGGGCC.
Mode of inheritance for STR: C9orf72_GGGGCC was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for STR: C9orf72_GGGGCC were set to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 105550
Childhood onset dystonia, chorea or related movement disorder v1.105 FXN_GAA Sarah Leigh changed review comment from: The FXN expansion has a well recognized association with Friedreich ataxia OMIM:229300; to: The FXN expansion has a well recognized association with Friedreich ataxia OMIM:229300

Comment from Zornitza Stark for FXN:
Primarily an ataxia, and also commonly caused by a GAA trinucleotide repeat expansion in intron 1 of the FXN gene.
Childhood onset dystonia, chorea or related movement disorder v1.105 FXN_GAA Sarah Leigh edited their review of STR: FXN_GAA: Added comment: The FXN expansion has a well recognized association with Friedreich ataxia OMIM:229300; Changed rating: GREEN; Changed publications to: 10399865, 8596916, 33670433
Childhood onset dystonia, chorea or related movement disorder v1.105 FXN_GAA Sarah Leigh Classified STR: FXN_GAA as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.105 FXN_GAA Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia, chorea or related movement disorder v1.105 FXN_GAA Sarah Leigh Str: fxn_gaa has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.103 GLRB Sarah Leigh Classified gene: GLRB as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.103 GLRB Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia, chorea or related movement disorder v1.103 GLRB Sarah Leigh Gene: glrb has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.100 UBTF Arina Puzriakova Classified gene: UBTF as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.100 UBTF Arina Puzriakova Added comment: Comment on list classification: There is sufficient evidence to promote this gene to Green status at the next GMS panel update
Childhood onset dystonia, chorea or related movement disorder v1.100 UBTF Arina Puzriakova Gene: ubtf has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.96 FITM2 Sarah Leigh Classified gene: FITM2 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.96 FITM2 Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia, chorea or related movement disorder v1.96 FITM2 Sarah Leigh Gene: fitm2 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.95 FITM2 Sarah Leigh Phenotypes for gene: FITM2 were changed from Siddiqi syndrome MIM#618635; dystonia; deafness to Siddiqi syndrome OMIM:618635; siddiqi syndrome MONDO:0032842
Childhood onset dystonia, chorea or related movement disorder v1.94 SCN1A Sarah Leigh Classified gene: SCN1A as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.94 SCN1A Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia, chorea or related movement disorder v1.94 SCN1A Sarah Leigh Gene: scn1a has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.92 SCN1A Dmitrijs Rots reviewed gene: SCN1A: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 28794249; Phenotypes: seizures, developmental delay, dystonia, choreoathetosis; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Childhood onset dystonia, chorea or related movement disorder v1.92 ALDH18A1 Sarah Leigh Phenotypes for gene: ALDH18A1 were changed from Cutis laxa, autosomal dominant 3 616603; Cutis laxa, autosomal recessive, type IIIA 219150; Spastic paraplegia 9A, autosomal dominant 601162; Spastic paraplegia 9B, autosomal recessive 616586 to Cutis laxa, autosomal dominant 3 OMIM:616603; cutis laxa, autosomal dominant 3 MONDO:0014706; Cutis laxa, autosomal recessive, type IIIA OMIM:219150; ALDH18A1-related de Barsy syndromeMONDO:0009053; Spastic paraplegia 9A, autosomal dominant OMIM:601162; hereditary spastic paraplegia 9A MONDO:0011006; Spastic paraplegia 9B, autosomal recessive OMIM:616586; autosomal recessive complex spastic paraplegia type 9B MONDO:0014702
Childhood onset dystonia, chorea or related movement disorder v1.90 TSPOAP1 Zornitza Stark gene: TSPOAP1 was added
gene: TSPOAP1 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Literature
Mode of inheritance for gene: TSPOAP1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TSPOAP1 were set to 33539324
Phenotypes for gene: TSPOAP1 were set to Dystonia, intellectual disability and cerebellar atrophy
Review for gene: TSPOAP1 was set to GREEN
Added comment: 7 affecteds from 3 families (1 consanguineous)
2x null, 1x missense

Affecteds with the null variants presented with juvenile-onset progressive generalized dystonia, associated with intellectual disability and cerebellar atrophy while those with the missense p.(Gly1808Ser) presented with isolated adult-onset focal dystonia (mild cognitive impairment noted). Mouse model.
Sources: Literature
Childhood onset dystonia, chorea or related movement disorder v1.90 IRF2BPL Sarah Leigh Classified gene: IRF2BPL as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.90 IRF2BPL Sarah Leigh Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia, chorea or related movement disorder v1.90 IRF2BPL Sarah Leigh Gene: irf2bpl has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.89 IRF2BPL Sarah Leigh Phenotypes for gene: IRF2BPL were changed from Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures, MIM# 618088 to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures OMIM:618088; neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures MONDO:0060759
Childhood onset dystonia, chorea or related movement disorder v1.87 CSTB Sarah Leigh Phenotypes for gene: CSTB were changed from microcephaly and severe dyskinesia; Epilepsy, progressive myoclonic 1A, 254800 to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) OMIM:254800; Unverricht-Lundborg syndrome MONDO:0009698
Childhood onset dystonia, chorea or related movement disorder v1.86 CLN5 Sarah Leigh Phenotypes for gene: CLN5 were changed from Ceroid lipofuscinosis, neuronal, 5, 256731 to Ceroid lipofuscinosis, neuronal, 5 OMIM:256731; neuronal ceroid lipofuscinosis 5 MONDO:0009745
Childhood onset dystonia, chorea or related movement disorder v1.85 MED27 Arina Puzriakova Classified gene: MED27 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.85 MED27 Arina Puzriakova Gene: med27 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.84 MED27 Arina Puzriakova gene: MED27 was added
gene: MED27 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Literature
Q2_21_rating tags were added to gene: MED27.
Mode of inheritance for gene: MED27 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: MED27 were set to 33443317
Phenotypes for gene: MED27 were set to Intellectual disability; Axial hypotonia; Spasticity; Dystonia; Cerebellar hypoplasia; Cataracts; Epilepsy
Review for gene: MED27 was set to GREEN
Added comment: MED27 is currently not associated with any phenotype in OMIM (last edited on 08/03/2012), but is listed in Gene2Phenotype with a 'probable' disease confidence rating for 'MED27-related neurodevelopmental disorder'

- PMID: 33443317 (2021) - 16 individuals from 11 families with a neurodevelopmental syndrome characterised by mild to profound GDD/ID (14/14), axial hypotonia (14/15), distal spasticity and dystonic movements (13/15), cerebellar hypoplasia (12/14), cataracts (10/15), epilepsy (9/15), and microcephaly (4/14). Exome sequencing revealed biallelic variants in the MED27 gene, including 3 recurrent variants found in 2 or more families with different background.

Overall sufficient (>3) unrelated cases for inclusion if phenotypes are considered to be within the scope of this panel - most individuals presented dystonic movements, but only 2 sibs experienced generalised dystonia.
Sources: Literature
Childhood onset dystonia, chorea or related movement disorder v1.82 VPS4A Arina Puzriakova Classified gene: VPS4A as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.82 VPS4A Arina Puzriakova Added comment: Comment on list classification: At least 5 different variants reported in 10 unrelated individuals with a comparable phenotype, including childhood onset dystonia in 9/10 cases. Pathogenicity is supported by functional data.

There is enough evidence to promote this gene to Green at the next GMS panel update (added 'for-review' tag)
Childhood onset dystonia, chorea or related movement disorder v1.82 VPS4A Arina Puzriakova Gene: vps4a has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.81 VPS4A Arina Puzriakova gene: VPS4A was added
gene: VPS4A was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Expert Review
for-review tags were added to gene: VPS4A.
Mode of inheritance for gene: VPS4A was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VPS4A were set to 33186545; 33186543; 33460484
Phenotypes for gene: VPS4A were set to CIMDAG syndrome
Review for gene: VPS4A was set to GREEN
Added comment: Gene currently not associated with any phenotype in OMIM (last edited: 20/12/2019) or Gene2Phenotype.

- PMID: 33186545 (2020) - Six unrelated individuals with de novo missense variants (c.850A>T, c.850A>G, c.616G>A) affecting the ATPase domain of VPS4A. Clinical features include severe DD and profound ID (6/6), hypotonia (5/6), microcephaly (6/6), dystonia (5/6), congenital cataracts (4/5), epilepsy (3/6), anaemia (3/6 - dyserythropoietic in 2), and structural brain abnormalities including cerebellar hypoplasia (5/6) or severe cerebral atrophy (1/6). Some functional data indicating a dominant-negative effect.

- PMID: 33186543 (2020) - Three unrelated individuals with congenital dyserythropoietic anaemia, severe neurodevelopmental delay, and dystonia. Two patients harboured different de novo variants (c.850A>T, c.608G>A) in the ATPase domain, while the third had a homozygous alteration (c.83C>T) occurring in the N-terminal microtubule interacting and trafficking domain of VPS4A. The first two individuals congenital microcephaly with brain MRI showing white matter and cerebral volume loss, thin corpus callosum, and ponto-cerebellar atrophy. One individual also displayed a seizure disorder and congenital cataracts. The case with the biallelic variant presented with a milder hematologic phenotype and had macrocephaly (rather than microcephaly) and delayed white matter myelination. Functional studies support pathogenicity.

- PMID: 33460484 (2021) - One child with a a severe neurodevelopmental disorder and congenital haemolytic anaemia but no overt sign of dyserythropoiesis, associated with a de novo variant (c.850A>T) in VPS4A. Other features include microcephaly (-2.5 SD), choreodystonic movements, and bilateral cataract. Brain MRI showed cerebral atrophy, thin dysplastic corpus callosum, basal ganglia atrophy, brainstem hypoplasia, cerebellar hypoplasia and dysplasia
Sources: Expert Review
Childhood onset dystonia, chorea or related movement disorder v1.78 ICK Arina Puzriakova Phenotypes for gene: ICK were changed from Endocrine-cerebroosteodysplasia, 612651; ECO; short-rib thoracic dysplasia with polydactyly (SRTD) to Endocrine-cerebroosteodysplasia, OMIM:612651; Endocrine-cerebro-osteodysplasia syndrome, MONDO:0012980
Childhood onset dystonia, chorea or related movement disorder v1.77 TOR1A Arina Puzriakova Phenotypes for gene: TOR1A were changed from Autosomal dominant or sporadic dystonia (DYT1); Early-Onset Primary Dystonia; Dystonia-1, torsion, 128100 to Dystonia-1, torsion, OMIM:128100; Dystonic disorder, MONDO:0003441
Childhood onset dystonia, chorea or related movement disorder v1.74 CACNB4 Sarah Leigh commented on gene: CACNB4: Associated with relevant phenotype in OMIM and as possible Gen2Phen gene. At least 3 variants reported in at least 3 unrelated cases, together with supportive functional data.
Childhood onset dystonia, chorea or related movement disorder v1.74 RNU7-1 Arina Puzriakova Classified gene: RNU7-1 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.74 RNU7-1 Arina Puzriakova Added comment: Comment on list classification: Rating Amber but should be promoted to Green at the next GMS panel update (added 'for-review' tag) - spastic dystonia was a feature in 9/16 patients (7 families) reported with biallelic variants in this gene (PMID:33230297)
Childhood onset dystonia, chorea or related movement disorder v1.74 RNU7-1 Arina Puzriakova Gene: rnu7-1 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.73 RNU7-1 Arina Puzriakova gene: RNU7-1 was added
gene: RNU7-1 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Literature
for-review tags were added to gene: RNU7-1.
Mode of inheritance for gene: RNU7-1 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: RNU7-1 were set to 33230297
Phenotypes for gene: RNU7-1 were set to Aicardi–Goutières syndrome-like; Type I interferonopathy
Review for gene: RNU7-1 was set to GREEN
Added comment: Not associated with any phenotype in OMIM or Gene2Phenotype.

- PMID: 33230297 (2020) - 16 individuals from 11 families with biallelic variants in the RNU7-1 gene. Clinical features were typical of Aicardi–Goutières syndrome, including spasticity, dystonia, epilepsy, peripheral neuropathy, brain calcification, mild skin involvement and delayed psychomotor development. Upregulated interferon signalling was detected in patient blood and fibroblasts. 4/12 variants were observed in 2 or more families - several from different ethnic backgrounds. 8 variants are recorded in gnomAD but at a frequency of ≤0.005, and no biallelic variants were identified in control populations. Some functional data showing a disturbance of histone RNA processing in patient-derived compared to control fibroblasts.
Sources: Literature
Childhood onset dystonia, chorea or related movement disorder v1.67 KCNMA1 Arina Puzriakova Phenotypes for gene: KCNMA1 were changed from Cerebellar atrophy, developmental delay, and seizures, 617643; Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, 609446 to Cerebellar atrophy, developmental delay, and seizures, OMIM:617643; Cerebellar atrophy, developmental delay, and seizures, MONDO:0060551; Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, OMIM:609446; Generalized epilepsy-paroxysmal dyskinesia syndrome, MONDO:0012276; Liang-Wang syndrome, OMIM:618729; Liang-Wang syndrome, MONDO:0032886
Childhood onset dystonia, chorea or related movement disorder v1.66 AASS Arina Puzriakova Phenotypes for gene: AASS were changed from Hyperlysinemia; Saccharopinuria, 268700 to Hyperlysinemia, OMIM:238700; Hyperlysinemia (disease), MONDO:0009388
Childhood onset dystonia, chorea or related movement disorder v1.65 AAAS Arina Puzriakova Phenotypes for gene: AAAS were changed from Achalasia-addisonianism-alacrimia syndrome, 231550 to Achalasia-addisonianism-alacrimia syndrome, OMIM:231550; Triple-A syndrome, MONDO:0009279
Childhood onset dystonia, chorea or related movement disorder v1.62 VPS41 Zornitza Stark gene: VPS41 was added
gene: VPS41 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Literature
Mode of inheritance for gene: VPS41 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS41 were set to 32808683
Phenotypes for gene: VPS41 were set to Dystonia; intellectual disability
Review for gene: VPS41 was set to RED
Added comment: Single individual reported with homozygous canonical splice site variant resulting in exon 7 skipping, and global developmental delay and generalized dystonia. He attained a few words and voluntary limb movements but never sat unsupported. He had pale optic discs and an axonal neuropathy. From 6 years of age, his condition began to deteriorate, with reduced motor abilities and alertness. An MRI of the brain showed atrophy of the superior cerebellar vermis and slimming of the posterior limb of the corpus callosum. VPS41 is component of the HOPS complex and other genes in the complex have been implicated in movement disorders.
Sources: Literature
Childhood onset dystonia, chorea or related movement disorder v1.62 VPS16 Zornitza Stark gene: VPS16 was added
gene: VPS16 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Literature
Mode of inheritance for gene: VPS16 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: VPS16 were set to 32808683
Phenotypes for gene: VPS16 were set to Dystonia
Review for gene: VPS16 was set to GREEN
Added comment: 18 individuals reported with high-impact variants in VPS16 and a progressive early onset dystonia (median age 12 years, range 3–50 years), with prominent oromandibular, bulbar, cervical, and upper limb involvement. Progressive generalization ensued, although most remained ambulant, and only a minority (16%) lost the ability to walk in adulthood.

Additional clinical features of mild to moderate intellectual disability and neuropsychiatric symptoms were present in approximately one‐third. In 4 individuals, magnetic resonance imaging (MRI) showed bilateral and symmetrical hypointensity of the globi pallidi and sometimes also the midbrain and dentate nuclei, suggestive of iron deposition. Mild generalized cerebral atrophy was also apparent in 4 individuals.
Sources: Literature
Childhood onset dystonia, chorea or related movement disorder v1.62 YIF1B Arina Puzriakova Classified gene: YIF1B as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.62 YIF1B Arina Puzriakova Added comment: Comment on list classification: There is a sufficient number of cases to rate this gene Green at the next major review.

Profound delay in motor development is part of the phenotype, as well as dystonia, spasticity and dyskinesia.
Childhood onset dystonia, chorea or related movement disorder v1.62 YIF1B Arina Puzriakova Gene: yif1b has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.61 YIF1B Arina Puzriakova gene: YIF1B was added
gene: YIF1B was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Expert list
for-review tags were added to gene: YIF1B.
Mode of inheritance for gene: YIF1B was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: YIF1B were set to 32006098
Phenotypes for gene: YIF1B were set to Central hypotonia; Failure to thrive; Microcephaly; Global developmental delay; Intellectual disability; Seizures; Spasticity; Abnormality of movement
Review for gene: YIF1B was set to GREEN
Added comment: - PMID: 32006098 - 6 individuals (from 5 families) with biallelic YIF1B truncating variants. Presenting features: hypotonia, failure to thrive, microcephaly (5/6), severe global DD and ID as well as features suggestive of a motor disorder including dystonia (5/6), spasticity (6/6), dyskinesia (5/5). Seizures were reported in 2 unrelated individuals (2/6). MRI abnormalities were observed in some with thin CC being a feature in 3.

Affected individuals were found to be homozygous for truncating variants (4/5 families being consanguineous). The following 3 variants were identified (NM_001039672.2) : c.186dupT or p.Ala64fs / c.360_361insACAT or p.Gly121fs / c.598G>T or p.Glu200*.

Yif1B KO mice demonstrate a disorganized Golgi architecture in pyramidal hippocampal neurons (Alterio et al 2015 - PMID: 26077767). Functional/network analysis of genes co-regulated with YIF1B based on available RNAseq data, suggest enrichment in genes important for nervous system development and function.
Sources: Expert list
Childhood onset dystonia, chorea or related movement disorder v1.59 Arina Puzriakova Panel version has been signed off
Childhood onset dystonia, chorea or related movement disorder v1.57 CSTB_CCCCGCCCCGCG Arina Puzriakova Classified STR: CSTB_CCCCGCCCCGCG as Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v1.57 CSTB_CCCCGCCCCGCG Arina Puzriakova Str: cstb_ccccgccccgcg has been classified as Green List (High Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.56 CSTB_CCCCGCCCCGCG Arina Puzriakova STR: CSTB_CCCCGCCCCGCG was added
STR: CSTB_CCCCGCCCCGCG was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Expert list
STR tags were added to STR: CSTB_CCCCGCCCCGCG.
Mode of inheritance for STR: CSTB_CCCCGCCCCGCG was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for STR: CSTB_CCCCGCCCCGCG were set to Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg), 254800
Review for STR: CSTB_CCCCGCCCCGCG was set to GREEN
Added comment: New STR submitted and discussed with GLHs for the GMS Neurology Specialist Test Group, who agreed that there is sufficient evidence to rate this STR Green on this panel.
Sources: Expert list
Childhood onset dystonia, chorea or related movement disorder v1.55 TBP_CAG Arina Puzriakova Classified STR: TBP_CAG as Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v1.55 TBP_CAG Arina Puzriakova Str: tbp_cag has been classified as Green List (High Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.53 ATXN2_CAG Arina Puzriakova Classified STR: ATXN2_CAG as Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v1.53 ATXN2_CAG Arina Puzriakova Str: atxn2_cag has been classified as Green List (High Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.51 TBC1D24 Zornitza Stark gene: TBC1D24 was added
gene: TBC1D24 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Expert list
Mode of inheritance for gene: TBC1D24 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: TBC1D24 were set to 31257402
Phenotypes for gene: TBC1D24 were set to Epilepsy, rolandic, with proxysmal exercise-induce dystonia and writer's cramp, MIM# 608105
Review for gene: TBC1D24 was set to GREEN
Added comment: Three unrelated families reported with rolandic epilepsy with paroxysmal exercise-induced dystonia and writer's cramp (EPRPDC), an autosomal recessive neurologic disorder characterised by onset of focal seizures in infancy and exercise-induced dystonia in childhood. Features usually include involuntary movements, including facial movements, and difficulties with fine motor skills of the hand. Seizures often respond to medication and remit with age; the dystonia tends to persist. Three unrelated families reported with this specific phenotype, though variants in this gene are associated with a range of other neurological disorders and may represent a spectrum of severity.
Sources: Expert list
Childhood onset dystonia, chorea or related movement disorder v1.51 SLC16A2 Zornitza Stark gene: SLC16A2 was added
gene: SLC16A2 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Expert list
Mode of inheritance for gene: SLC16A2 was set to X-LINKED: hemizygous mutation in males, biallelic mutations in females
Publications for gene: SLC16A2 were set to 31410843
Phenotypes for gene: SLC16A2 were set to Allan-Herndon-Dudley syndrome, MIM# 300523
Review for gene: SLC16A2 was set to GREEN
gene: SLC16A2 was marked as current diagnostic
Added comment: Allan-Herndon-Dudley syndrome (AHDS) is an X-linked condition characterized by severely impaired intellectual development, dysarthria, athetoid movements, muscle hypoplasia, and spastic paraplegia. There is large phenotypic interfamilial and intrafamilial variability. In a recent review of 24 affected individuals (PMID 31410843), 16 presented with profound developmental delay, three had severe intellectual disability with poor language and walking with an aid, four had moderate intellectual disability with language and walking abilities, and one had mild intellectual disability with hypotonia. Overall, eight had learned to walk, all had hypotonia, 17 had spasticity, 18 had dystonia, 12 had choreoathetosis, 19 had hypomyelination, and 10 had brain atrophy. Kyphoscoliosis (n=12), seizures (n=7), and pneumopathies (n=5) were the most severe complications.
Sources: Expert list
Childhood onset dystonia, chorea or related movement disorder v1.51 HNRNPH1 Arina Puzriakova Classified gene: HNRNPH1 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.51 HNRNPH1 Arina Puzriakova Added comment: Comment on list classification: There is enough evidence to rate this gene GREEN at the next major review - two studies report de novo variants in at least 6 unrelated cases with a movement phenotype.
Childhood onset dystonia, chorea or related movement disorder v1.51 HNRNPH1 Arina Puzriakova Gene: hnrnph1 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.49 IRF2BPL Zornitza Stark gene: IRF2BPL was added
gene: IRF2BPL was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Expert list
Mode of inheritance for gene: IRF2BPL was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: IRF2BPL were set to 30057031; 30166628
Phenotypes for gene: IRF2BPL were set to Neurodevelopmental disorder with regression, abnormal movements, loss of speech, and seizures, MIM# 618088
Review for gene: IRF2BPL was set to GREEN
gene: IRF2BPL was marked as current diagnostic
Added comment: PMID: 30057031 - 7 individuals with neurodevelopmental regression (5/7), progressive ataxia (5/7), seizures (7/7), spasticity (2/7), dystonia (3/7) and global devel delay (7/7). PTCs produced a more severe phenotype than missense. Onset was in childhood. Cerebellar changes also less frequently reported.

PMID: 30166628 - 11 individuals with de novo PTCs with childhood neurological regression, epilepsy (7/11), hypotonia (5/11), dystonia (3/11), cerebellar atrophy (5/10). MRI showed CNS defects in 6/10 patients.
Sources: Expert list
Childhood onset dystonia, chorea or related movement disorder v1.49 GRIN1 Zornitza Stark gene: GRIN1 was added
gene: GRIN1 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Expert list
Mode of inheritance for gene: GRIN1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Publications for gene: GRIN1 were set to 29365063; 27164704; 27164704; 28051072
Phenotypes for gene: GRIN1 were set to Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal dominant, MIM# 614254; Neurodevelopmental disorder with or without hyperkinetic movements and seizures, autosomal recessive, MIM# 617820
Review for gene: GRIN1 was set to GREEN
gene: GRIN1 was marked as current diagnostic
Added comment: Over 20 individuals reported with de novo missense variants in GRIN1 and severe neurodevelopmental phenotype, comprising ID, seizures, and a movement disorder, in particular dystonia. Two families reported with bi-allelic variants: different mechanism postulated (LOF vs affecting channel functioning or hypomorphic alleles), parents were carriers and unaffected. Movement disorder, in particular dystonia also reported in bi-allelic cases.
Sources: Expert list
Childhood onset dystonia, chorea or related movement disorder v1.49 GNB1 Zornitza Stark gene: GNB1 was added
gene: GNB1 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Expert list
Mode of inheritance for gene: GNB1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: GNB1 were set to 27108799; 30194818; 27668284; 31034681
Phenotypes for gene: GNB1 were set to Mental retardation, autosomal dominant 42, MIM# 616973
Review for gene: GNB1 was set to GREEN
gene: GNB1 was marked as current diagnostic
Added comment: Multiple reports of dystonia in this disorder. In a recent series of 18 individuals with de novo mutations, the most observed substitution affected the p.Ile80 residue in exon 6, with 28% of individuals carrying a variant at this residue. Dystonia and growth delay were observed more frequently in individuals carrying variants in this residue, suggesting a potential genotype-phenotype correlation.
Sources: Expert list
Childhood onset dystonia, chorea or related movement disorder v1.49 FUCA1 Zornitza Stark reviewed gene: FUCA1: Rating: GREEN; Mode of pathogenicity: None; Publications: 31064022; Phenotypes: Fucosidosis, MIM#230000; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v1.49 FITM2 Zornitza Stark gene: FITM2 was added
gene: FITM2 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Expert list
Mode of inheritance for gene: FITM2 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FITM2 were set to 28067622; 30214770; 30288795
Phenotypes for gene: FITM2 were set to Siddiqi syndrome MIM#618635; dystonia; deafness
Review for gene: FITM2 was set to GREEN
gene: FITM2 was marked as current diagnostic
Added comment: 7 cases from 3 unrelated families (2 consanguineous) with a dystonia-deafness syndrome and a supporting Drosophila model.
Sources: Expert list
Childhood onset dystonia, chorea or related movement disorder v1.49 CSTB Zornitza Stark reviewed gene: CSTB: Rating: AMBER; Mode of pathogenicity: None; Publications: ; Phenotypes: Epilepsy, progressive myoclonic 1A (Unverricht and Lundborg) 254800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v1.49 C9orf72 Zornitza Stark changed review comment from: Dystonia is well described but this appears to be an adult-onset disorder.; to: Dystonia is well described but this appears to be an adult-onset disorder. Also note condition is caused by heterozygous hexanucleotide repeat expansion (GGGGCC) in a noncoding region of the C9ORF72 gene.
Childhood onset dystonia, chorea or related movement disorder v1.49 C9orf72 Zornitza Stark reviewed gene: C9orf72: Rating: RED; Mode of pathogenicity: None; Publications: 26166205, 24363131, 26187722; Phenotypes: Frontotemporal dementia and/or amyotrophic lateral sclerosis 1, MIM# 105550; Mode of inheritance: None
Childhood onset dystonia, chorea or related movement disorder v1.49 ALDH18A1 Zornitza Stark reviewed gene: ALDH18A1: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Spastic paraplegia 9B, autosomal recessive, MIM# 616586, Spastic paraplegia 9A, autosomal dominant, MIM# 601162; Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v1.49 AFG3L2 Zornitza Stark reviewed gene: AFG3L2: Rating: RED; Mode of pathogenicity: None; Publications: 22964162, 16541453; Phenotypes: Spastic ataxia 5, autosomal recessive MIM#614487; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v1.49 Eleanor Williams Panel version has been signed off
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TY Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TW Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TV Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TT Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TS2 Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TS1 Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TR Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TQ Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TP Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TN Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TM Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TL2 Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TL1 Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TI Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TH Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TG Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TF Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TE Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TD Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TA Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-RNR2 Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-RNR1 Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-ND4L Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-ND2 Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-CYB Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-CO2 Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-CO1 Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-ATP8 Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from red to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TK Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from green to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TC Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from green to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-ND6 Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from green to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-ND5 Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from green to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-ND4 Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from green to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-ND3 Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from green to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-ND1 Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from green to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-CO3 Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from green to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-ATP6 Eleanor Williams changed review comment from: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop.; to: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop. Rating changed from green to grey.
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TY Eleanor Williams Classified gene: MT-TY as No list
Childhood onset dystonia, chorea or related movement disorder v1.45 MT-TY Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.44 MT-TW Eleanor Williams Classified gene: MT-TW as No list
Childhood onset dystonia, chorea or related movement disorder v1.44 MT-TW Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.43 MT-TV Eleanor Williams Classified gene: MT-TV as No list
Childhood onset dystonia, chorea or related movement disorder v1.43 MT-TV Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.42 MT-TT Eleanor Williams Classified gene: MT-TT as No list
Childhood onset dystonia, chorea or related movement disorder v1.42 MT-TT Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.41 MT-TS2 Eleanor Williams Classified gene: MT-TS2 as No list
Childhood onset dystonia, chorea or related movement disorder v1.41 MT-TS2 Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.40 MT-TS1 Eleanor Williams Classified gene: MT-TS1 as No list
Childhood onset dystonia, chorea or related movement disorder v1.40 MT-TS1 Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.39 MT-TR Eleanor Williams Classified gene: MT-TR as No list
Childhood onset dystonia, chorea or related movement disorder v1.39 MT-TR Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.38 MT-TQ Eleanor Williams Classified gene: MT-TQ as No list
Childhood onset dystonia, chorea or related movement disorder v1.38 MT-TQ Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.37 MT-TP Eleanor Williams Classified gene: MT-TP as No list
Childhood onset dystonia, chorea or related movement disorder v1.37 MT-TP Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.36 MT-TN Eleanor Williams Classified gene: MT-TN as No list
Childhood onset dystonia, chorea or related movement disorder v1.36 MT-TN Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.35 MT-TM Eleanor Williams Classified gene: MT-TM as No list
Childhood onset dystonia, chorea or related movement disorder v1.35 MT-TM Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.34 MT-TL2 Eleanor Williams Classified gene: MT-TL2 as No list
Childhood onset dystonia, chorea or related movement disorder v1.34 MT-TL2 Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.33 MT-TL1 Eleanor Williams Classified gene: MT-TL1 as No list
Childhood onset dystonia, chorea or related movement disorder v1.33 MT-TL1 Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.32 MT-TI Eleanor Williams Classified gene: MT-TI as No list
Childhood onset dystonia, chorea or related movement disorder v1.32 MT-TI Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.31 MT-TH Eleanor Williams Classified gene: MT-TH as No list
Childhood onset dystonia, chorea or related movement disorder v1.31 MT-TH Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.30 MT-TG Eleanor Williams Classified gene: MT-TG as No list
Childhood onset dystonia, chorea or related movement disorder v1.30 MT-TG Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.29 MT-TF Eleanor Williams Classified gene: MT-TF as No list
Childhood onset dystonia, chorea or related movement disorder v1.29 MT-TF Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.28 MT-TE Eleanor Williams Classified gene: MT-TE as No list
Childhood onset dystonia, chorea or related movement disorder v1.28 MT-TE Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.27 MT-TD Eleanor Williams Classified gene: MT-TD as No list
Childhood onset dystonia, chorea or related movement disorder v1.27 MT-TD Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.26 MT-TA Eleanor Williams Classified gene: MT-TA as No list
Childhood onset dystonia, chorea or related movement disorder v1.26 MT-TA Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.25 MT-RNR2 Eleanor Williams Classified gene: MT-RNR2 as No list
Childhood onset dystonia, chorea or related movement disorder v1.25 MT-RNR2 Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.24 MT-RNR1 Eleanor Williams Classified gene: MT-RNR1 as No list
Childhood onset dystonia, chorea or related movement disorder v1.24 MT-RNR1 Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.23 MT-ND4L Eleanor Williams Classified gene: MT-ND4L as No list
Childhood onset dystonia, chorea or related movement disorder v1.23 MT-ND4L Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.22 MT-ND2 Eleanor Williams Classified gene: MT-ND2 as No list
Childhood onset dystonia, chorea or related movement disorder v1.22 MT-ND2 Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.21 MT-CYB Eleanor Williams Classified gene: MT-CYB as No list
Childhood onset dystonia, chorea or related movement disorder v1.21 MT-CYB Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.20 MT-CO2 Eleanor Williams Classified gene: MT-CO2 as No list
Childhood onset dystonia, chorea or related movement disorder v1.20 MT-CO2 Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.19 MT-CO1 Eleanor Williams Classified gene: MT-CO1 as No list
Childhood onset dystonia, chorea or related movement disorder v1.19 MT-CO1 Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.18 MT-ATP8 Eleanor Williams Classified gene: MT-ATP8 as No list
Childhood onset dystonia, chorea or related movement disorder v1.18 MT-ATP8 Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.17 MT-TK Eleanor Williams Classified gene: MT-TK as No list
Childhood onset dystonia, chorea or related movement disorder v1.17 MT-TK Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.16 MT-TC Eleanor Williams Classified gene: MT-TC as No list
Childhood onset dystonia, chorea or related movement disorder v1.16 MT-TC Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.15 MT-ND6 Eleanor Williams Classified gene: MT-ND6 as No list
Childhood onset dystonia, chorea or related movement disorder v1.15 MT-ND6 Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.14 MT-ND5 Eleanor Williams Classified gene: MT-ND5 as No list
Childhood onset dystonia, chorea or related movement disorder v1.14 MT-ND5 Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.13 MT-ND4 Eleanor Williams Classified gene: MT-ND4 as No list
Childhood onset dystonia, chorea or related movement disorder v1.13 MT-ND4 Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.12 MT-ND3 Eleanor Williams Classified gene: MT-ND3 as No list
Childhood onset dystonia, chorea or related movement disorder v1.12 MT-ND3 Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.11 MT-ND1 Eleanor Williams Classified gene: MT-ND1 as No list
Childhood onset dystonia, chorea or related movement disorder v1.11 MT-ND1 Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.10 MT-CO3 Eleanor Williams Classified gene: MT-CO3 as No list
Childhood onset dystonia, chorea or related movement disorder v1.10 MT-CO3 Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop
Childhood onset dystonia, chorea or related movement disorder v1.9 MT-ATP6 Eleanor Williams Classified gene: MT-ATP6 as No list
Childhood onset dystonia, chorea or related movement disorder v1.9 MT-ATP6 Eleanor Williams Added comment: Comment on list classification: Mitochondrial gene removed from the panel at the request of NHS England following discussion at a Rare Disease workshop.
Childhood onset dystonia, chorea or related movement disorder v1.8 EIF2AK2 Arina Puzriakova Classified gene: EIF2AK2 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.8 EIF2AK2 Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.
Childhood onset dystonia, chorea or related movement disorder v1.8 EIF2AK2 Arina Puzriakova Gene: eif2ak2 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.7 EIF2AK2 Arina Puzriakova gene: EIF2AK2 was added
gene: EIF2AK2 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Literature
for-review tags were added to gene: EIF2AK2.
Mode of inheritance for gene: EIF2AK2 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: EIF2AK2 were set to 32197074
Phenotypes for gene: EIF2AK2 were set to Leukoencephalopathy, developmental delay, and episodic neurologic regression syndrome, 618877
Review for gene: EIF2AK2 was set to GREEN
Added comment: Association with Developmental Delay, Leukoencephalopathy, and Neurologic Decompensation reported in both OMIM and G2P (probable).

PMID: 32197074 (2020) - Distinct de novo missense variants were identified in eight unrelated individuals who all share a notable phenotypic overlap of developmental delay, cognitive impairment, white matter alterations, dysarthria or lack of speech, and neurologic regression with febrile illness. Other variable features included hypotonia (7/8), hypertonia (7/8), ataxia (6/8), dystonia (5/8), tremor (3/8) and seizures (4/8). Functional data confirm reduced kinase activity compared to the wildtype protein product, and authors predict a dominant-negative effect.
Sources: Literature
Childhood onset dystonia, chorea or related movement disorder v1.6 NDUFA2 Arina Puzriakova Classified gene: NDUFA2 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.6 NDUFA2 Arina Puzriakova Added comment: Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review - at least three unrelated cases presenting a movement phenotype following a period of regression.
Childhood onset dystonia, chorea or related movement disorder v1.6 NDUFA2 Arina Puzriakova Gene: ndufa2 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.5 NDUFA2 Arina Puzriakova Classified gene: NDUFA2 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v1.5 NDUFA2 Arina Puzriakova Gene: ndufa2 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v1.3 DDC Lothar Schlueter reviewed gene: DDC: Rating: GREEN; Mode of pathogenicity: None; Publications: 28100251, 30952622; Phenotypes: Aromatic L-amino acid decarboxylase deficiency 608643, floppy child, dystonia, hypotonia, developmental delay, oculogyric crisis; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v1.3 Catherine Snow Panel version has been signed off
Childhood onset dystonia, chorea or related movement disorder v1.0 Louise Daugherty promoted panel to version 1.0
Childhood onset dystonia, chorea or related movement disorder v0.259 Louise Daugherty Panel types changed to GMS Rare Disease Virtual; GMS Rare Disease; GMS signed-off
Childhood onset dystonia, chorea or related movement disorder v0.258 TPK1 Louise Daugherty Classified gene: TPK1 as Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v0.258 TPK1 Louise Daugherty Added comment: Comment on list classification: Changed from Red to Green as per recommendation from Specialist Test Group (via Robyn Labrum LNGLH). Reported in multiple families
Childhood onset dystonia, chorea or related movement disorder v0.258 TPK1 Louise Daugherty Gene: tpk1 has been classified as Green List (High Evidence).
Childhood onset dystonia, chorea or related movement disorder v0.257 GNAL Louise Daugherty Classified gene: GNAL as Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v0.257 GNAL Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green as per recommendation from Specialist Test Group (via Robyn Labrum LNGLH) 12 December 2019. Multiple unrelated families
Childhood onset dystonia, chorea or related movement disorder v0.257 GNAL Louise Daugherty Gene: gnal has been classified as Green List (High Evidence).
Childhood onset dystonia, chorea or related movement disorder v0.256 ACTB Louise Daugherty changed review comment from: Comment on list classification: Changed from Amber to Green as per recommendation from Specialist Test Group (via Robyn Labrum LNGLH).
Despite the evidence in the literature not supporting a Green rating the Specialist Test Group still supported a Green rating based on limited evidence – juvenile onset dystonia, only identified in 1 family, twins, brains examined post mortem; to: Comment on list classification: Changed from Amber to Green as per recommendation from Specialist Test Group (via Robyn Labrum LNGLH) 12 December 2019.
Despite the evidence in the literature not supporting a Green rating the Specialist Test Group still supported a Green rating based on limited evidence – juvenile onset dystonia, only identified in 1 family, twins, brains examined post mortem
Childhood onset dystonia, chorea or related movement disorder v0.256 ACTB Louise Daugherty Classified gene: ACTB as Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v0.256 ACTB Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green as per recommendation from Specialist Test Group (via Robyn Labrum LNGLH).
Despite the evidence in the literature not supporting a Green rating the Specialist Test Group still supported a Green rating based on limited evidence – juvenile onset dystonia, only identified in 1 family, twins, brains examined post mortem
Childhood onset dystonia, chorea or related movement disorder v0.256 ACTB Louise Daugherty Gene: actb has been classified as Green List (High Evidence).
Childhood onset dystonia, chorea or related movement disorder v0.249 SCN8A Louise Daugherty Phenotypes for gene: SCN8A were changed from paroxysmal kinesigenic dyskinesias; epilepsy to paroxysmal kinesigenic dyskinesias; epilepsy, Seizures, benign familial infantile, 5, 617080
Childhood onset dystonia, chorea or related movement disorder v0.247 PRRT2 Louise Daugherty Phenotypes for gene: PRRT2 were changed from CONVULSIONS, FAMILIAL INFANTILE, WITH PAROXYSMAL CHOREOATHETOSIS; SEIZURES, BENIGN FAMILIAL INFANTILE, 2; Episodic kinesigenic dyskinesia 1, 128200; dystonia and occasionally hemiplegic migraine and epilepsy; Paroxysmal kinesigenic choreoathetosis (PKD1) and infantile convulsions; episodic kinesigenic dyskinesia to Convulsions, familial infantile, with paroxysmal choreoathetosis, 602066; Episodic kinesigenic dyskinesia 1, 128200; dystonia and occasionally hemiplegic migraine and epilepsy; Paroxysmal kinesigenic choreoathetosis (PKD1) and infantile convulsions; episodic kinesigenic dyskinesia
Childhood onset dystonia, chorea or related movement disorder v0.234 MRE11 Louise Daugherty Phenotypes for gene: MRE11 were changed from Ataxia-telangiectasia-like disorder 1 to Ataxia-telangiectasia-like disorder 1, 604391
Childhood onset dystonia, chorea or related movement disorder v0.233 MARS2 Louise Daugherty Phenotypes for gene: MARS2 were changed from Spastic ataxia 3, autosomal recessive to Spastic ataxia 3, autosomal recessive, 611390
Childhood onset dystonia, chorea or related movement disorder v0.231 KIF1C Louise Daugherty Phenotypes for gene: KIF1C were changed from Spastic ataxia 2, autosomal recessive to Spastic ataxia 2, autosomal recessive, 611302
Childhood onset dystonia, chorea or related movement disorder v0.230 KCNMA1 Louise Daugherty Phenotypes for gene: KCNMA1 were changed from Cerebellar atrophy, developmental delay, and seizures; Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy to Cerebellar atrophy, developmental delay, and seizures, 617643; Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy, 609446
Childhood onset dystonia, chorea or related movement disorder v0.226 GM2A Louise Daugherty Phenotypes for gene: GM2A were changed from GM2-gangliosidosis, AB variant to GM2-gangliosidosis, AB variant, 272750
Childhood onset dystonia, chorea or related movement disorder v0.225 GLB1 Louise Daugherty Phenotypes for gene: GLB1 were changed from GM1-gangliosidosis to GM1-gangliosidosis, type III, 230650
Childhood onset dystonia, chorea or related movement disorder v0.224 GJC2 Louise Daugherty Phenotypes for gene: GJC2 were changed from Spastic paraplegia 44, autosomal recessive; Leukodystrophy, hypomyelinating, 2 to Spastic paraplegia 44, autosomal recessive, 613206; Leukodystrophy, hypomyelinating, 2, 608804
Childhood onset dystonia, chorea or related movement disorder v0.213 VPS13D Louise Daugherty Phenotypes for gene: VPS13D were changed from Spinocerebellar ataxia, autosomal recessive 4 to Spinocerebellar ataxia, autosomal recessive 4, 607317
Childhood onset dystonia, chorea or related movement disorder v0.209 FBXO7 Louise Daugherty Phenotypes for gene: FBXO7 were changed from juvenile parkinsonism; Dystonia to Parkinson disease 15, autosomal recessive, 260300; juvenile parkinsonism; Dystonia
Childhood onset dystonia, chorea or related movement disorder v0.205 CSTB Louise Daugherty Phenotypes for gene: CSTB were changed from microcephaly and severe dyskinesia; Epilepsy, progressive myoclonic 1A, 254800 to microcephaly and severe dyskinesia; Epilepsy, progressive myoclonic 1A, 254800
Childhood onset dystonia, chorea or related movement disorder v0.205 CSTB Louise Daugherty Phenotypes for gene: CSTB were changed from microcephaly and severe dyskinesia (26843564); Epilepsy, progressive myoclonic 1A, 254800 to microcephaly and severe dyskinesia; Epilepsy, progressive myoclonic 1A, 254800
Childhood onset dystonia, chorea or related movement disorder v0.202 CLN5 Louise Daugherty Phenotypes for gene: CLN5 were changed from Ceroid lipofuscinosis, neuronal, 5 to Ceroid lipofuscinosis, neuronal, 5, 256731
Childhood onset dystonia, chorea or related movement disorder v0.201 CLN3 Louise Daugherty Phenotypes for gene: CLN3 were changed from Ceroid lipofuscinosis, neuronal, 3 to Ceroid lipofuscinosis, neuronal, 3, 204200
Childhood onset dystonia, chorea or related movement disorder v0.199 ATM Louise Daugherty Phenotypes for gene: ATM were changed from Dystonia; Ataxia telangiectasia to Dystonia; Ataxia telangiectasia, 208900
Childhood onset dystonia, chorea or related movement disorder v0.196 WWOX Louise Daugherty Phenotypes for gene: WWOX were changed from to Spinocerebellar ataxia, autosomal recessive 12, 614322
Childhood onset dystonia, chorea or related movement disorder v0.190 TPP1 Louise Daugherty Phenotypes for gene: TPP1 were changed from to Spinocerebellar ataxia, autosomal recessive 7, 609270
Childhood onset dystonia, chorea or related movement disorder v0.184 STUB1 Louise Daugherty Phenotypes for gene: STUB1 were changed from to Spinocerebellar ataxia, autosomal recessive 16, 615768
Childhood onset dystonia, chorea or related movement disorder v0.180 SNX14 Louise Daugherty Phenotypes for gene: SNX14 were changed from to Spinocerebellar ataxia, autosomal recessive 20, 616354
Childhood onset dystonia, chorea or related movement disorder v0.179 SIL1 Louise Daugherty Mode of inheritance for gene: SIL1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder v0.178 SIL1 Louise Daugherty Phenotypes for gene: SIL1 were changed from to Marinesco-Sjogren syndrome, 248800
Childhood onset dystonia, chorea or related movement disorder v0.162 GRM1 Louise Daugherty Phenotypes for gene: GRM1 were changed from to Spinocerebellar ataxia 44, 617691; Spinocerebellar ataxia, autosomal recessive 13, 614831
Childhood onset dystonia, chorea or related movement disorder v0.159 GRID2 Louise Daugherty Phenotypes for gene: GRID2 were changed from Spinocerebellar ataxia, autosomal recessive 18 to Spinocerebellar ataxia, autosomal recessive 18, 616204
Childhood onset dystonia, chorea or related movement disorder v0.158 GRID2 Louise Daugherty Phenotypes for gene: GRID2 were changed from Spinocerebellar ataxia, autosomal recessive 18 to Spinocerebellar ataxia, autosomal recessive 18
Childhood onset dystonia, chorea or related movement disorder v0.158 GRID2 Louise Daugherty Phenotypes for gene: GRID2 were changed from Spinocerebellar ataxia, autosomal recessive 18 to Spinocerebellar ataxia, autosomal recessive 18
Childhood onset dystonia, chorea or related movement disorder v0.158 GRID2 Louise Daugherty Phenotypes for gene: GRID2 were changed from Spinocerebellar ataxia, autosomal recessive 18 to Spinocerebellar ataxia, autosomal recessive 18
Childhood onset dystonia, chorea or related movement disorder v0.158 GRID2 Louise Daugherty Phenotypes for gene: GRID2 were changed from Spinocerebellar ataxia, autosomal recessive 18 to Spinocerebellar ataxia, autosomal recessive 18
Childhood onset dystonia, chorea or related movement disorder v0.158 GRID2 Louise Daugherty Phenotypes for gene: GRID2 were changed from Spinocerebellar ataxia, autosomal recessive 18 to Spinocerebellar ataxia, autosomal recessive 18
Childhood onset dystonia, chorea or related movement disorder v0.158 GRID2 Louise Daugherty Phenotypes for gene: GRID2 were changed from Spinocerebellar ataxia, autosomal recessive 18 to Spinocerebellar ataxia, autosomal recessive 18
Childhood onset dystonia, chorea or related movement disorder v0.158 GRID2 Louise Daugherty Phenotypes for gene: GRID2 were changed from to Spinocerebellar ataxia, autosomal recessive 18
Childhood onset dystonia, chorea or related movement disorder v0.154 ELOVL4 Louise Daugherty Phenotypes for gene: ELOVL4 were changed from to Ichthyosis, spastic quadriplegia, and mental retardation, 614457
Childhood onset dystonia, chorea or related movement disorder v0.152 DNAJC5 Louise Daugherty Phenotypes for gene: DNAJC5 were changed from to Ceroid lipofuscinosis, neuronal, 4, Parry type, 162350
Childhood onset dystonia, chorea or related movement disorder v0.148 CWF19L1 Louise Daugherty Phenotypes for gene: CWF19L1 were changed from to Spinocerebellar ataxia, autosomal recessive 17, 616127
Childhood onset dystonia, chorea or related movement disorder v0.146 CTSD Louise Daugherty Phenotypes for gene: CTSD were changed from to Ceroid lipofuscinosis, neuronal, 10, 610127
Childhood onset dystonia, chorea or related movement disorder v0.144 CLN8 Louise Daugherty Phenotypes for gene: CLN8 were changed from to Ceroid lipofuscinosis, neuronal, 8, 600143
Childhood onset dystonia, chorea or related movement disorder v0.131 ANO10 Louise Daugherty Phenotypes for gene: ANO10 were changed from to Spinocerebellar ataxia, autosomal recessive 10, 613728
Childhood onset dystonia, chorea or related movement disorder v0.127 ABCB7 Louise Daugherty Phenotypes for gene: ABCB7 were changed from to Anemia, sideroblastic, with ataxia, 301310
Childhood onset dystonia, chorea or related movement disorder v0.125 AASS Louise Daugherty Phenotypes for gene: AASS were changed from to Hyperlysinemia; Saccharopinuria, 268700
Childhood onset dystonia, chorea or related movement disorder v0.123 AAAS Louise Daugherty Phenotypes for gene: AAAS were changed from to Achalasia-addisonianism-alacrimia syndrome, 231550
Childhood onset dystonia, chorea or related movement disorder v0.121 VAMP2 Louise Daugherty changed review comment from: Comment on phenotypes: Phenotype from Salpietro et al. Am J Hum Genet. 2019 Apr 4;104(4):721-730) de novo mutations in 5 unrelated individuals phenotype neurodevelopmental disorder characterized by axial hypotonia (which had been present since birth), intellectual disability, and autistic features. More severe phenotype includes additional neurological features, including central visual impairment, hyperkinetic movement disorder, and epilepsy or electroencephalography abnormalities. ?Better on intellectual disability or neurodevelopmental panel. Needs clinical input.; to: Comment on phenotypes: Phenotype from Salpietro et al. Am J Hum Genet. 2019 Apr 4;104(4):721-730) de novo mutations in 5 unrelated individuals phenotype neurodevelopmental disorder characterized by axial hypotonia (which had been present since birth), intellectual disability, and autistic features. More severe phenotype includes additional neurological features, including central visual impairment, hyperkinetic movement disorder, and epilepsy or electroencephalography abnormalities
Childhood onset dystonia, chorea or related movement disorder v0.121 VAMP2 Louise Daugherty Added comment: Comment on phenotypes: Phenotype from Salpietro et al. Am J Hum Genet. 2019 Apr 4;104(4):721-730) de novo mutations in 5 unrelated individuals phenotype neurodevelopmental disorder characterized by axial hypotonia (which had been present since birth), intellectual disability, and autistic features. More severe phenotype includes additional neurological features, including central visual impairment, hyperkinetic movement disorder, and epilepsy or electroencephalography abnormalities. ?Better on intellectual disability or neurodevelopmental panel. Needs clinical input.
Childhood onset dystonia, chorea or related movement disorder v0.119 GNAL Louise Daugherty changed review comment from: Comment on list classification: downgraded until Specialist Test Group review - need more evidence; to: Comment on list classification: downgraded until Specialist Test Group review rating in view of age of onset Average age at onset 31 years (range 7 to 54)

Monoallelic mutations have been associated with adult-onset cranio-cervical dystonia - PMID: 23222958 (more than 2 families with adult onset of focal dystonia (plus plus neck), which often progresses to involve other regions), 23449625 (4 families with reduced penetrance, adult onset of focal dystonia), 23759320 (2 chinese families and sporadic adult onset generalized dystonia), 24151159 (3 sporadic cases with adult-onset dystonia involving the neck and or face), 24408567 (1 sporadic case adult-onset dystonia), 24535567 (2 families with craniocervical dystonia), 24729450 (1 sporadic cervical dystonia, DE NOVO), 25382112 (2 sporadic with dystonia) plus other similar publications. ONE BIALLELIC MUTATION described in 27222887 1 girl from cons parents with generalised dystonia and mild ID.
Childhood onset dystonia, chorea or related movement disorder v0.119 GNAL Louise Daugherty Classified gene: GNAL as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v0.119 GNAL Louise Daugherty Added comment: Comment on list classification: downgraded until Specialist Test Group review - need more evidence
Childhood onset dystonia, chorea or related movement disorder v0.119 GNAL Louise Daugherty Gene: gnal has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v0.118 ZSWIM6 Louise Daugherty Phenotypes for gene: ZSWIM6 were changed from Acromelic frontonasal dysostosis 603671 to Neurodevelopmental disorder with movement abnormalities, abnormal gait, and autistic features, 617865
Childhood onset dystonia, chorea or related movement disorder v0.113 OCLN Louise Daugherty Phenotypes for gene: OCLN were changed from Band-like calcification with simplified gyration and polymicrogyria 251290 to Band-like calcification with simplified gyration and polymicrogyria, 251290
Childhood onset dystonia, chorea or related movement disorder v0.112 HEXA Louise Daugherty Phenotypes for gene: HEXA were changed from [Hex A pseudodeficiency] 272800 AR; GM2-gangliosidosis, several forms 272800; Tay-Sachs disease 272800 to Hex A pseudodeficiency, 272800 AR; GM2-gangliosidosis, several forms, 272800; Tay-Sachs disease, 272800
Childhood onset dystonia, chorea or related movement disorder v0.111 ADCY5 Louise Daugherty Phenotypes for gene: ADCY5 were changed from Dyskinesia, familial, with facial myokymia, 606703; dystonia; Familial dyskinesia 606703 to Dyskinesia, familial, with facial myokymia, 606703; dystonia; Familial dyskinesia, 606703
Childhood onset dystonia, chorea or related movement disorder v0.106 PDE2A Ellen McDonagh Added comment: Comment on mode of inheritance: Based on Paroxysmal central nervous system disorders gene panel, version 1.0.
Childhood onset dystonia, chorea or related movement disorder v0.102 VPS13D Ellen McDonagh Phenotypes for gene: VPS13D were changed from to Spinocerebellar ataxia, autosomal recessive 4
Childhood onset dystonia, chorea or related movement disorder v0.96 SETX Ellen McDonagh Phenotypes for gene: SETX were changed from to Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2
Childhood onset dystonia, chorea or related movement disorder v0.75 MRE11 Ellen McDonagh Phenotypes for gene: MRE11 were changed from to Ataxia-telangiectasia-like disorder 1
Childhood onset dystonia, chorea or related movement disorder v0.73 MARS2 Ellen McDonagh Phenotypes for gene: MARS2 were changed from to Spastic ataxia 3, autosomal recessive
Childhood onset dystonia, chorea or related movement disorder v0.68 KIF1C Ellen McDonagh Phenotypes for gene: KIF1C were changed from to Spastic ataxia 2, autosomal recessive
Childhood onset dystonia, chorea or related movement disorder v0.65 KCNMA1 Ellen McDonagh Phenotypes for gene: KCNMA1 were changed from to Cerebellar atrophy, developmental delay, and seizures; Paroxysmal nonkinesigenic dyskinesia, 3, with or without generalized epilepsy
Childhood onset dystonia, chorea or related movement disorder v0.57 GM2A Ellen McDonagh Phenotypes for gene: GM2A were changed from to GM2-gangliosidosis, AB variant
Childhood onset dystonia, chorea or related movement disorder v0.55 GLB1 Ellen McDonagh Phenotypes for gene: GLB1 were changed from to GM1-gangliosidosis
Childhood onset dystonia, chorea or related movement disorder v0.54 GJC2 Ellen McDonagh Phenotypes for gene: GJC2 were changed from Spastic paraplegia 44, autosomal recessive to Spastic paraplegia 44, autosomal recessive; Leukodystrophy, hypomyelinating, 2
Childhood onset dystonia, chorea or related movement disorder v0.53 GJC2 Ellen McDonagh Phenotypes for gene: GJC2 were changed from to Spastic paraplegia 44, autosomal recessive
Childhood onset dystonia, chorea or related movement disorder v0.39 CLN5 Ellen McDonagh Phenotypes for gene: CLN5 were changed from to Ceroid lipofuscinosis, neuronal, 5
Childhood onset dystonia, chorea or related movement disorder v0.37 CLN3 Ellen McDonagh Phenotypes for gene: CLN3 were changed from to Ceroid lipofuscinosis, neuronal, 3
Childhood onset dystonia, chorea or related movement disorder v0.32 C9orf72 Ellen McDonagh Phenotypes for gene: C9orf72 were changed from to Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 105550
Childhood onset dystonia, chorea or related movement disorder v0.31 ALDH18A1 Ellen McDonagh Phenotypes for gene: ALDH18A1 were changed from to Cutis laxa, autosomal dominant 3 616603; Cutis laxa, autosomal recessive, type IIIA 219150; Spastic paraplegia 9A, autosomal dominant 601162; Spastic paraplegia 9B, autosomal recessive 616586
Childhood onset dystonia, chorea or related movement disorder v0.29 AFG3L2 Ellen McDonagh Phenotypes for gene: AFG3L2 were changed from Dystonia to Spastic ataxia 5, autosomal recessive 614487; Spinocerebellar ataxia 28 610246
Childhood onset dystonia, chorea or related movement disorder v0.23 TPK1 Ellen McDonagh Classified gene: TPK1 as Red List (low evidence)
Childhood onset dystonia, chorea or related movement disorder v0.23 TPK1 Ellen McDonagh Added comment: Comment on list classification: Kept as Red, as only one patient reported with dystonia, and one Red review.
Childhood onset dystonia, chorea or related movement disorder v0.23 TPK1 Ellen McDonagh Gene: tpk1 has been classified as Red List (Low Evidence).
Childhood onset dystonia, chorea or related movement disorder v0.21 RNASEH2A Ellen McDonagh Classified gene: RNASEH2A as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v0.21 RNASEH2A Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Amber due to review from North Bristol NHS Trust (South West GLH). Requires clinical input to determine whether appropriate to include and promote to Green.
Childhood onset dystonia, chorea or related movement disorder v0.21 RNASEH2A Ellen McDonagh Gene: rnaseh2a has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v0.20 PLP1 Ellen McDonagh Classified gene: PLP1 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v0.20 PLP1 Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Amber due to review from North Bristol NHS Trust (South West GLH).
Childhood onset dystonia, chorea or related movement disorder v0.20 PLP1 Ellen McDonagh Gene: plp1 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v0.18 AUH Ellen McDonagh Classified gene: AUH as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v0.18 AUH Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Amber due to review from North Bristol NHS Trust (South West GLH). Clinical input required to decide whether this is appropriate to include and to make this Green.
Childhood onset dystonia, chorea or related movement disorder v0.18 AUH Ellen McDonagh Gene: auh has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v0.17 SUOX Ellen McDonagh Classified gene: SUOX as Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v0.17 SUOX Ellen McDonagh Added comment: Comment on list classification: Promoted this gene from Red to Green due to review from North Bristol NHS Trust (South West GLH).
Childhood onset dystonia, chorea or related movement disorder v0.17 SUOX Ellen McDonagh Gene: suox has been classified as Green List (High Evidence).
Childhood onset dystonia, chorea or related movement disorder v0.16 PCDH12 Ellen McDonagh Classified gene: PCDH12 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v0.16 PCDH12 Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Amber due to the review from North Bristol NHS Trust (South West GLH) - ataxia/dystonia can be a feature. More evidence or clinical review required for this to be Green.
Childhood onset dystonia, chorea or related movement disorder v0.16 PCDH12 Ellen McDonagh Gene: pcdh12 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v0.15 NKX2-1 Ellen McDonagh Classified gene: NKX2-1 as Green List (high evidence)
Childhood onset dystonia, chorea or related movement disorder v0.15 NKX2-1 Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Green due to review by North Bristol NHS Trust (South West GLH) to suggest that this is a well described syndrome.
Childhood onset dystonia, chorea or related movement disorder v0.15 NKX2-1 Ellen McDonagh Gene: nkx2-1 has been classified as Green List (High Evidence).
Childhood onset dystonia, chorea or related movement disorder v0.14 L2HGDH Ellen McDonagh Classified gene: L2HGDH as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v0.14 L2HGDH Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Amber due to review from North Bristol NHS Trust. Requires clinical input.
Childhood onset dystonia, chorea or related movement disorder v0.14 L2HGDH Ellen McDonagh Gene: l2hgdh has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v0.13 HPRT1 Ellen McDonagh Classified gene: HPRT1 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v0.13 HPRT1 Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Amber due to review from North Bristol NHS Trust. Clinical input required to promote to Green.
Childhood onset dystonia, chorea or related movement disorder v0.13 HPRT1 Ellen McDonagh Gene: hprt1 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v0.12 FOXG1 Ellen McDonagh Classified gene: FOXG1 as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v0.12 FOXG1 Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Amber due to review from North Bristol NHS Trust.
Childhood onset dystonia, chorea or related movement disorder v0.12 FOXG1 Ellen McDonagh Gene: foxg1 has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v0.11 ARX Ellen McDonagh Classified gene: ARX as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v0.11 ARX Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Amber due to review; for further clinical review.
Childhood onset dystonia, chorea or related movement disorder v0.11 ARX Ellen McDonagh Gene: arx has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v0.9 ACTB Ellen McDonagh Classified gene: ACTB as Amber List (moderate evidence)
Childhood onset dystonia, chorea or related movement disorder v0.9 ACTB Ellen McDonagh Added comment: Comment on list classification: Promoted from Red to Amber, as there has only been one variant reported.
Childhood onset dystonia, chorea or related movement disorder v0.9 ACTB Ellen McDonagh Gene: actb has been classified as Amber List (Moderate Evidence).
Childhood onset dystonia, chorea or related movement disorder v0.7 ZSWIM6 Ellen McDonagh Source PanelApp was added to ZSWIM6.
Mode of inheritance for gene ZSWIM6 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Mode of pathogenicity for gene ZSWIM6 was changed from to Other - please provide details in the comments
Added phenotypes Acromelic frontonasal dysostosis 603671 for gene: ZSWIM6
Publications for gene ZSWIM6 were changed from to 25105228
Childhood onset dystonia, chorea or related movement disorder v0.7 TOR1A Ellen McDonagh Source PanelApp was added to TOR1A.
Mode of inheritance for gene TOR1A was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Autosomal dominant or sporadic dystonia (DYT1); Early-Onset Primary Dystonia; Dystonia-1, torsion, 128100 for gene: TOR1A
Publications for gene TOR1A were changed from to 20301334; 11523564; 17503336; 20301665; 9288096; 16537570
Childhood onset dystonia, chorea or related movement disorder v0.7 THAP1 Ellen McDonagh Source PanelApp was added to THAP1.
Mode of inheritance for gene THAP1 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Dystonia 6, torsion, 602629; Dystonia for gene: THAP1
Publications for gene THAP1 were changed from to 20301334
Childhood onset dystonia, chorea or related movement disorder v0.7 SCN8A Ellen McDonagh Source PanelApp was added to SCN8A.
Mode of inheritance for gene SCN8A was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes paroxysmal kinesigenic dyskinesias; epilepsy for gene: SCN8A
Publications for gene SCN8A were changed from to 26677014
Childhood onset dystonia, chorea or related movement disorder v0.7 SCN1A Ellen McDonagh Source PanelApp was added to SCN1A.
Mode of inheritance for gene SCN1A was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes several epilepsy, convulsion and migraine disorders.; familial hemiplegic migraine 3; Dravet syndrome for gene: SCN1A
Publications for gene SCN1A were changed from to 19332696; 16054936
Childhood onset dystonia, chorea or related movement disorder v0.7 PRRT2 Ellen McDonagh Source PanelApp was added to PRRT2.
Mode of inheritance for gene PRRT2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes CONVULSIONS, FAMILIAL INFANTILE, WITH PAROXYSMAL CHOREOATHETOSIS; SEIZURES, BENIGN FAMILIAL INFANTILE, 2; Episodic kinesigenic dyskinesia 1, 128200; dystonia and occasionally hemiplegic migraine and epilepsy; Paroxysmal kinesigenic choreoathetosis (PKD1) and infantile convulsions; episodic kinesigenic dyskinesia for gene: PRRT2
Publications for gene PRRT2 were changed from to 22744660; 20301334; 22399141; 22120146; 22101681
Childhood onset dystonia, chorea or related movement disorder v0.7 PNKD Ellen McDonagh Source PanelApp was added to PNKD.
Mode of inheritance for gene PNKD was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Familial Paroxysmal Nonkinesigenic Dyskinesia; PAROXYSMAL NONKINESIGENIC DYSKINESIA 1; Paroxysmal nonkinesigenic dyskinesia, 118800 for gene: PNKD
Publications for gene PNKD were changed from to 15496428; 20301334; 15262732; 15824259
Childhood onset dystonia, chorea or related movement disorder v0.7 NKX2-1 Ellen McDonagh Source PanelApp was added to NKX2-1.
Added phenotypes Choreoathetosis, hypothyroidism, and neonatal respiratory distress 610978; Chorea, hereditary benign 118700 for gene: NKX2-1
Publications for gene NKX2-1 were changed from to 24555207
Childhood onset dystonia, chorea or related movement disorder v0.7 ATP1A2 Ellen McDonagh Source PanelApp was added to ATP1A2.
Mode of inheritance for gene ATP1A2 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes familial basilar migraine 602481; familial hemiplegic migraine type 2, 602481; alternating hemiplegia of childhood 104290; Dystonia; migraine for gene: ATP1A2
Publications for gene ATP1A2 were changed from to 18056581; 12953268; 12539047
Childhood onset dystonia, chorea or related movement disorder v0.7 ADCY5 Ellen McDonagh Source PanelApp was added to ADCY5.
Mode of inheritance for gene ADCY5 was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Added phenotypes Dyskinesia, familial, with facial myokymia, 606703; dystonia; Familial dyskinesia 606703 for gene: ADCY5
Publications for gene ADCY5 were changed from to 11310626; 24700542
Childhood onset dystonia, chorea or related movement disorder v0.7 TUBB4A Ellen McDonagh Source PanelApp was added to TUBB4A.
Mode of inheritance for gene TUBB4A was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes hereditary whispering dysphonia; ?Dystonia 4, torsion, autosomal dominant, 128101; Dystonia; Leukodystrophy, hypomyelinating, 6 612438 for gene: TUBB4A
Publications for gene TUBB4A were changed from to 27809427; 24850488; 23582646; 24526230
Childhood onset dystonia, chorea or related movement disorder v0.7 CHMP2B Ellen McDonagh Source PanelApp was added to CHMP2B.
Mode of inheritance for gene CHMP2B was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Frontotemporal dementia and/or amyotrophic lateral sclerosis 1; Dystonia; familial frontotemporal lobar degeneration (ALS17) for gene: CHMP2B
Childhood onset dystonia, chorea or related movement disorder v0.7 ANO3 Ellen McDonagh Source PanelApp was added to ANO3.
Mode of inheritance for gene ANO3 was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Added phenotypes Dystonia 24, 615034; familial form of cranio-cervical dystonia for gene: ANO3
Publications for gene ANO3 were changed from to 25847575; 24151159 Low frequency missense variants in ANO3 occur in both cases and controls, warranting further assessment of this gene in PTD pathogenesis; 23200863; 24094724 Rare variants in ANO3 are not a susceptibility factor in essential tremor; 27392807; 24442708
Childhood onset dystonia, chorea or related movement disorder v0.7 ZNF423 Ellen McDonagh Source PanelApp was added to ZNF423.
Mode of inheritance for gene ZNF423 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Added phenotypes Joubert syndrome 19; Nephronophthisis 14; Nephronophthisis 14, 614844; Joubert syndrome 19, 614844; Joubert syndrome with oculorenal defect for gene: ZNF423
Childhood onset dystonia, chorea or related movement disorder v0.7 SPR Ellen McDonagh Source PanelApp was added to SPR.
Mode of inheritance for gene SPR was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Added phenotypes Dopa-Responsive Dystonia; Movement disorder, autonomic dysfunction, developmental delay, behavioural difficulties; Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, 612716; Sepiapterin reductase deficiency; paediatric form of dopa responsive dystonia for gene: SPR
Publications for gene SPR were changed from to 15241655; 18502672; 27830117; 20301334; 11443547; 22522443; 27604308
Childhood onset dystonia, chorea or related movement disorder v0.7 SLC2A1 Ellen McDonagh Source PanelApp was added to SLC2A1.
Mode of inheritance for gene SLC2A1 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Added phenotypes GLUT1 deficiency syndrome 2, childhood onset; dystonia 9; EPILEPSY, IDIOPATHIC GENERALIZED; GLUT1 deficiency syndrome 1, 606777; GLUT1 deficiency syndrome 1, infantile onset, severe; Dystonia; paroxysmal exertion-induced dyskinesia with or without epilepsy and/or hemolytic anemia; GLUT1 deficiency syndrome 2 for gene: SLC2A1
Publications for gene SLC2A1 were changed from to 19630075; 20301334; 18451999; 18577546
Childhood onset dystonia, chorea or related movement disorder v0.7 GCH1 Ellen McDonagh Source PanelApp was added to GCH1.
Mode of inheritance for gene GCH1 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Added phenotypes Dopa-Responsive Dystonia (DRD); Hyperphenylalaninemia, BH4-deficient, B, 233910; Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230; GTP-cyclohydrolase deficiency for gene: GCH1
Publications for gene GCH1 were changed from to 3762960; 8163996; 7730309; 10987649; 942621; 9667588; 3822637; 7874165; 17111153; 6734669; 1899474; 945938; 3400489; 7869202; 10208576; 20301334; 27830117; 12552057; 20301681; 10732814; 12084887; 3041760; 16908750; 11346370; 11113234; 2296384; 15753436
Childhood onset dystonia, chorea or related movement disorder v0.7 VPS13A Ellen McDonagh Source PanelApp was added to VPS13A.
Mode of inheritance for gene VPS13A was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Choreoacanthocytosis 200150; complex parkinsonism for gene: VPS13A
Publications for gene VPS13A were changed from to 14663054; 11381253; 11381254
Childhood onset dystonia, chorea or related movement disorder v0.7 TMEM67 Ellen McDonagh Source PanelApp was added to TMEM67.
Mode of inheritance for gene TMEM67 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes 613550; 607361; Joubert syndrome; ?Bardet-Biedl syndrome?; 216360; Joubert syndrome 6; Meckel-Gruber syndrome; Meckel syndrome; COACH syndrome; nephronophthisis; Senior-Boichis syndrome; 610688; Nephronophthisis 11 for gene: TMEM67
Publications for gene TMEM67 were changed from to PMID: 17160906; PMID: 19058225; PMID: 20607301; PMID: 16415887; PMID: 18327255; PMID: 19508969
Childhood onset dystonia, chorea or related movement disorder v0.7 TH Ellen McDonagh Source PanelApp was added to TH.
Mode of inheritance for gene TH was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes DOPA-responsive dystonia; Segawa syndrome, recessive, 605407; Tyrosine Hydroxylase Deficiency; Segawa syndrome; paediatric form of dopa responsive dystonia for gene: TH
Publications for gene TH were changed from to 27830117; 20301334; 8528210; 21937992; 9732974; 9703425; 8817341; 17696123; 7814018; 11246459; 10585338
Childhood onset dystonia, chorea or related movement disorder v0.7 SLC30A10 Ellen McDonagh Source PanelApp was added to SLC30A10.
Mode of inheritance for gene SLC30A10 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, and Chronic Liver Disease; Hypermanganesemia with dystonia, polycythemia, and cirrhosis, 613280 for gene: SLC30A10
Publications for gene SLC30A10 were changed from to 22934317; 22341972; 25778823; 22341971; 22926781
Childhood onset dystonia, chorea or related movement disorder v0.7 SLC25A19 Ellen McDonagh Source PanelApp was added to SLC25A19.
Mode of inheritance for gene SLC25A19 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Microcephaly, Amish type 607196; Thiamine metabolism dysfunction syndrome 4 (progressive polyneuropathy type) 613710 for gene: SLC25A19
Publications for gene SLC25A19 were changed from to 19798730; 12185364; 17035501
Childhood onset dystonia, chorea or related movement disorder v0.7 SLC19A3 Ellen McDonagh Source PanelApp was added to SLC19A3.
Mode of inheritance for gene SLC19A3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Dystonia; Thiamine metabolism dysfunction syndrome 2 (biotin- or thiamine-responsive encephalopathy type 2) 607483 for gene: SLC19A3
Childhood onset dystonia, chorea or related movement disorder v0.7 SLC18A2 Ellen McDonagh Source PanelApp was added to SLC18A2.
Mode of inheritance for gene SLC18A2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Brain Dopamine Serotonin Vesicular Transport Disease (Other disorders of neurotransmitter metabolism); Vesicular monoamine transporter deficiency for gene: SLC18A2
Publications for gene SLC18A2 were changed from to 27830117; 28477711; 26497564; 23363473; 27520881; 24398404; 24018103; 27604308
Childhood onset dystonia, chorea or related movement disorder v0.7 SERAC1 Ellen McDonagh Source PanelApp was added to SERAC1.
Mode of inheritance for gene SERAC1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Lesions in the basal ganglia; MEGDEL syndrome; MEGDHEL syndrome; Dystonia; 3-methylglutaconic aciduria with deafness, encephalopathy, and Leigh-like syndrome, 614739; 3-MEthylGlutaconic aciduria, Dystonia-Deafness, Hepatopathy, Encephalopathy, Leigh-like syndrome for gene: SERAC1
Publications for gene SERAC1 were changed from to 27186703; 16527507; 28482397; 28778788; 29205472; 22683713; 27604308
Childhood onset dystonia, chorea or related movement disorder v0.7 PRKRA Ellen McDonagh Source PanelApp was added to PRKRA.
Mode of inheritance for gene PRKRA was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Dystonia 16, 612067; early-Onset Generalized dystonia-parkinsonism (DYT16), non-responsive to levo-dopa; Dystonia for gene: PRKRA
Publications for gene PRKRA were changed from to 22842711; 25737287; 20301334; 18420150; 18243799; 26990861; 25914261; 24142417; 25142429
Childhood onset dystonia, chorea or related movement disorder v0.7 PLA2G6 Ellen McDonagh Source PanelApp was added to PLA2G6.
Mode of inheritance for gene PLA2G6 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Parkinson disease 14, autosomal recessive 612953; Infantile neuroaxonal dystrophy 1 256600; Neurodegeneration with brain iron accumulation 2B 610217; PLA2G6-associated neurodegeneration for gene: PLA2G6
Publications for gene PLA2G6 were changed from to 16783378; 18799783; 18570303
Childhood onset dystonia, chorea or related movement disorder v0.7 PDE10A Ellen McDonagh Source PanelApp was added to PDE10A.
Mode of inheritance for gene PDE10A was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Striatal degeneration, autosomal dominant 616922; Dyskinesia, limb and orofacial, infantile-onset 616921 for gene: PDE10A
Publications for gene PDE10A were changed from to 27058447; 27058446
Childhood onset dystonia, chorea or related movement disorder v0.7 PARK7 Ellen McDonagh Source PanelApp was added to PARK7.
Added phenotypes Parkinson disease 7, autosomal recessive early-onset for gene: PARK7
Childhood onset dystonia, chorea or related movement disorder v0.7 OCLN Ellen McDonagh Source PanelApp was added to OCLN.
Mode of inheritance for gene OCLN was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Band-like calcification with simplified gyration and polymicrogyria 251290 for gene: OCLN
Publications for gene OCLN were changed from to 20727516
Childhood onset dystonia, chorea or related movement disorder v0.7 NPHP3 Ellen McDonagh Source PanelApp was added to NPHP3.
Mode of inheritance for gene NPHP3 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Nephronophthisis 3, 604387; Senior-Loken syndrome; Renal-hepatic-pancreatic dysplasia 1, 208540; Nephronophthisis; Meckel syndrome 7, 267010; Renal-hepatic-pancreatic dysplasia for gene: NPHP3
Childhood onset dystonia, chorea or related movement disorder v0.7 NPHP1 Ellen McDonagh Source PanelApp was added to NPHP1.
Mode of inheritance for gene NPHP1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Joubert syndrome 4; 609583 Nephronophthisis 1, juvenile; Senior-Loken syndrome; 256100 Senior-Loken syndrome-1, 266900; Nephronophthisis for gene: NPHP1
Publications for gene NPHP1 were changed from to 15689444; 15138899; 22982934
Childhood onset dystonia, chorea or related movement disorder v0.7 NKX6-2 Ellen McDonagh Source PanelApp was added to NKX6-2.
Mode of inheritance for gene NKX6-2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Spastic ataxia 8, autosomal recessive, with hypomyelinating leukodystrophy 617560 for gene: NKX6-2
Publications for gene NKX6-2 were changed from to 15601927; 28575651
Childhood onset dystonia, chorea or related movement disorder v0.7 MKS1 Ellen McDonagh Source PanelApp was added to MKS1.
Mode of inheritance for gene MKS1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Mode of pathogenicity for gene MKS1 was changed from to Other - please provide details in the comments
Added phenotypes polydactyly; Joubert syndrome 28; Joubert syndrome; polycystic kidneys; occipital encephalocele; Meckel-Gruber syndrome; 249000; renal fibrosis; Meckel syndrome; Bardet-Biedl syndrome for gene: MKS1
Publications for gene MKS1 were changed from to 18327255; 26490104; 24886560; 17437276; 16415886
Childhood onset dystonia, chorea or related movement disorder v0.7 KIAA0586 Ellen McDonagh Source PanelApp was added to KIAA0586.
Mode of inheritance for gene KIAA0586 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Short-rib thoracic dysplasia 14 with polydactyly; Joubert syndrome; Joubert syndrome 23; Short-rib dysplasia 14 with polydactyly for gene: KIAA0586
Publications for gene KIAA0586 were changed from to 26096313
Childhood onset dystonia, chorea or related movement disorder v0.7 ICK Ellen McDonagh Source PanelApp was added to ICK.
Mode of inheritance for gene ICK was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Endocrine-cerebroosteodysplasia, 612651; ECO; short-rib thoracic dysplasia with polydactyly (SRTD) for gene: ICK
Publications for gene ICK were changed from to 27466187; 19185282; 27069622
Childhood onset dystonia, chorea or related movement disorder v0.7 HYLS1 Ellen McDonagh Source PanelApp was added to HYLS1.
Mode of inheritance for gene HYLS1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Joubert syndrome; Hydrolethalus syndrome, 236680 for gene: HYLS1
Publications for gene HYLS1 were changed from to 18648327 - Hydrolethalus syndrome; 19656802 - impairment in ciligenesis; 15843405 - Hydrolethalus syndrome; 26830932 - report in two siblings with Joubert syndrome
Childhood onset dystonia, chorea or related movement disorder v0.7 HPCA Ellen McDonagh Source PanelApp was added to HPCA.
Mode of inheritance for gene HPCA was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes adolescence-onset segmental dystonia; generalized dystonia with additional neurological features; Dystonia 2, torsion, autosomal recessive, 224500; childhood-onset generalized dystonia for gene: HPCA
Publications for gene HPCA were changed from to 25799108; 30145809
Childhood onset dystonia, chorea or related movement disorder v0.7 FA2H Ellen McDonagh Source PanelApp was added to FA2H.
Mode of inheritance for gene FA2H was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes fatty acid hydroxylase-associated neurodegeneration; Dystonia; Spastic paraplegia 35, autosomal recessive 612319 for gene: FA2H
Publications for gene FA2H were changed from to 19068277
Childhood onset dystonia, chorea or related movement disorder v0.7 EVC2 Ellen McDonagh Source PanelApp was added to EVC2.
Mode of inheritance for gene EVC2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Ellis-van Creveld syndrome, 225500; Weyers acrofacial dysostosis, 193530 for gene: EVC2
Childhood onset dystonia, chorea or related movement disorder v0.7 EVC Ellen McDonagh Source PanelApp was added to EVC.
Mode of inheritance for gene EVC was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Ellis-van Creveld syndrome, 225500; Weyers acrodental dysostosis, 193530 for gene: EVC
Childhood onset dystonia, chorea or related movement disorder v0.7 CSTB Ellen McDonagh Source PanelApp was added to CSTB.
Mode of inheritance for gene CSTB was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes microcephaly and severe dyskinesia (26843564); Epilepsy, progressive myoclonic 1A, 254800 for gene: CSTB
Publications for gene CSTB were changed from to 26843564
Childhood onset dystonia, chorea or related movement disorder v0.7 CP Ellen McDonagh Source PanelApp was added to CP.
Mode of inheritance for gene CP was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Cerebellar ataxia 604290; Dystonia; [Hypoceruloplasminemia, hereditary] 604290; Aceruloplasminemia; Hemosiderosis, systemic, due to aceruloplasminemia 604290 for gene: CP
Childhood onset dystonia, chorea or related movement disorder v0.7 CENPF Ellen McDonagh Source PanelApp was added to CENPF.
Mode of inheritance for gene CENPF was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Stromme syndrome, 243605; Lethal fetal brain malformation-duodenal atresia-bilateral renal hypoplasia syndrome for gene: CENPF
Publications for gene CENPF were changed from to 26820108
Childhood onset dystonia, chorea or related movement disorder v0.7 ATM Ellen McDonagh Source PanelApp was added to ATM.
Mode of inheritance for gene ATM was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Dystonia; Ataxia telangiectasia for gene: ATM
Childhood onset dystonia, chorea or related movement disorder v0.1 VPS37A Ellen McDonagh gene: VPS37A was added
gene: VPS37A was added to Childhood onset dystonia or chorea or related movement disorder. Sources: South West GLH
Mode of inheritance for gene: VPS37A was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: VPS37A were set to Spastic paraplegia 53, autosomal recessive, 614898
Childhood onset dystonia, chorea or related movement disorder v0.1 TREM2 Ellen McDonagh gene: TREM2 was added
gene: TREM2 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: South West GLH
Mode of inheritance for gene: TREM2 was set to
Phenotypes for gene: TREM2 were set to Polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy 2, 618193; Alzheimers disease; Frontotemporal dementia
Childhood onset dystonia, chorea or related movement disorder v0.1 SCN9A Ellen McDonagh gene: SCN9A was added
gene: SCN9A was added to Childhood onset dystonia or chorea or related movement disorder. Sources: South West GLH
Mode of inheritance for gene: SCN9A was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: SCN9A were set to Paroxysmal extreme pain disorder, 167400; Erythermalgia, Primary; Erythermalgia, primary, 133020; Hereditary Sensory Neuropathy; Insensitivity to pain, channelopathy-associated, 243000; Congenital Indifference to Pain; Epilepsy, generalized, with febrile seizures plus, type 7, 613863; Dysosteosclerosis; Febrile seizures, familial, 3B, 613863; Paroxysmal Extreme Pain Disorder
Childhood onset dystonia, chorea or related movement disorder v0.1 PITX3 Ellen McDonagh gene: PITX3 was added
gene: PITX3 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: South West GLH
Mode of inheritance for gene: PITX3 was set to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Phenotypes for gene: PITX3 were set to Disorders of Dopamine Synthesis Regulation
Childhood onset dystonia, chorea or related movement disorder v0.1 PDX1 Ellen McDonagh gene: PDX1 was added
gene: PDX1 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: South West GLH
Mode of inheritance for gene: PDX1 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PDX1 were set to Pancreatic agenesis 1 260370; MODY, type IV 606392
Childhood onset dystonia, chorea or related movement disorder v0.1 PARK7 Ellen McDonagh gene: PARK7 was added
gene: PARK7 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: South West GLH
Mode of inheritance for gene: PARK7 was set to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: PARK7 were set to Parkinson disease 7, autosomal recessive early-onset
Childhood onset dystonia, chorea or related movement disorder v0.1 MCOLN1 Ellen McDonagh Source South West GLH was added to MCOLN1.
Mode of inheritance for gene MCOLN1 was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Mucolipidosis IV, 252650 for gene: MCOLN1
Childhood onset dystonia, chorea or related movement disorder v0.1 MAT1A Ellen McDonagh Source South West GLH was added to MAT1A.
Mode of inheritance for gene MAT1A was changed from to Unknown
Added phenotypes Hypermethioninemia, persistent, autosomal dominant, due to methionine adenosyltransferase I/III deficiency, 250850 for gene: MAT1A
Childhood onset dystonia, chorea or related movement disorder v0.1 ATN1 Ellen McDonagh gene: ATN1 was added
gene: ATN1 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: South West GLH
Mode of inheritance for gene: ATN1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: ATN1 were set to Dentatorubro-pallidoluysian atrophy, 125370
Childhood onset dystonia, chorea or related movement disorder v0.1 TREX1 Ellen McDonagh Source South West GLH was added to TREX1.
Mode of inheritance for gene TREX1 was changed from to BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Added phenotypes Vasculopathy, retinal, with cerebral leukodystrophy, 192315; Aicardi-Goutieres syndrome 1, dominant and recessive, 225750 for gene: TREX1
Childhood onset dystonia, chorea or related movement disorder v0.1 HEXA Ellen McDonagh Source South West GLH was added to HEXA.
Mode of inheritance for gene HEXA was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes [Hex A pseudodeficiency] 272800 AR; GM2-gangliosidosis, several forms 272800; Tay-Sachs disease 272800 for gene: HEXA
Childhood onset dystonia, chorea or related movement disorder v0.1 CYP27A1 Ellen McDonagh Source South West GLH was added to CYP27A1.
Mode of inheritance for gene CYP27A1 was changed from to Unknown
Added phenotypes Cerebrotendinous xanthomatosis, CTX, 213700 for gene: CYP27A1
Childhood onset dystonia, chorea or related movement disorder v0.1 NKX2-1 Ellen McDonagh gene: NKX2-1 was added
gene: NKX2-1 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: South West GLH
Mode of inheritance for gene: NKX2-1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: NKX2-1 were set to Choreoathetosis, hypothyroidism, and neonatal respiratory distress 610978; Chorea, hereditary benign 118700
Childhood onset dystonia, chorea or related movement disorder v0.0 SI Ellen McDonagh gene: SI was added
gene: SI was added to Childhood onset dystonia or chorea or related movement disorder. Sources: London North GLH,Expert Review Red
Mode of inheritance for gene: SI was set to
Childhood onset dystonia, chorea or related movement disorder v0.0 SIL1 Ellen McDonagh gene: SIL1 was added
gene: SIL1 was added to Childhood onset dystonia or chorea or related movement disorder. Sources: Expert Review Amber,London North GLH
Mode of inheritance for gene: SIL1 was set to