Complex Parkinsonism (includes pallido-pyramidal syndromes) (Version 0.55)

This Panel is marked as Internal

Description

Inclusion criteria:
- Progressive motor syndrome with parkinsonism (bradykinesia with one of tremor, gait disorder, stiffness)
- Additional features may include spasticity, gaze palsy, early dementia, early bulbar failure, dyspraxia, ataxia, postural hypotension, cortical sensory loss, brain iron accumulation on MRI brain
- Age at onset ≤45 years or later onset with family history of similar condition in other family members

Exclusion criteria:
- Underlying cause not identified, e.g. structural brain lesion, Wilson disease

Prior Genetic Testing:
- Results should have been reviewed for all genetic tests undertaken. This includes review of available exome sequencing data, but where this is the case can be limited to genes specified within disease-relevant in silico panels. The patient is not eligible if a pathogenic variant has been identified in any gene related to their phenotype.
- Standard local genetic testing and nationally commissioned testing for this phenotype should have been completed AND
- Testing should be undertaken for any individual gene for which diagnostic yield is >10% for this phenotype AND
- The following specific gene tests are advised as a means of limiting the re- discovery of recognised pathogenic variants that could be more efficiently identified through the existing catalogue of UKGTN tests:
- C9ORF72, GRN, MAPT in cases with a clinical presentation suggestive of
cortico-basal/PSP syndrome

These requirements will be kept under continual review during the main programme and may be subject to change

Panel Activity

4 reviewers

Ellen McDonagh (Genomics England Curator)

Group: Other
Workplace: Other
alisdair mcneill (Sheffield childrens hospital)

Group: NHS Genomic Medicine Centre
Workplace: NHS clinical service
Alice Gardham (Genomics England)

Group: Other
Workplace: Other
Louise Daugherty (Genomics England Curator)

Group: Other
Workplace: Other

48 Entities

33 reviewed, 24 green

List	Entity	Reviews	Mode of inheritance	Details
Filter Entities 48 Entitiess
Green Green List (high evidence)	ANO3	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Green Phenotypes Dystonia 24, 615034 familial form of cranio-cervical dystonia Tags
Green Green List (high evidence)	ATP13A2	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Kufor-Rakeb Syndrome Parkinson disease 9, 606693 Tags
Green Green List (high evidence)	ATP1A3	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Phenotypes Rapid-Onset Dystonia-Parkinsonism Tags
Green Green List (high evidence)	C19orf12	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Dystonia mitochondrial membrane protein-associated neurodegeneration Tags
Green Green List (high evidence)	DCTN1	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Expert Review Green Tags
Green Green List (high evidence)	FBXO7	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Early Onset Complex Disease Parkinson disease 15, autosomal recessive, 260300 Parkinson Disease, Recessive Tags
Green Green List (high evidence)	GCH1	1 review	BOTH monoallelic and biallelic, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Dystonia, DOPA-responsive, with or without hyperphenylalaninemia, 128230 Hyperphenylalaninemia, BH4-deficient, B, 233910 Dopa-Responsive Dystonia (DRD) Tags
Green Green List (high evidence)	LRRK2	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Parkinson disease 8, 607060 Parkinson Disease, Dominant Parkinson Disease 8, Autosomal Dominant PARKINSON DISEASE 8, AUTOSOMAL DOMINANT Tags
Green Green List (high evidence)	MAPT	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Eligibility statement prior genetic testing Expert Expert Review Green Radboud University Medical Center, Nijmegen UKGTN Phenotypes Dementia, frontotemporal, with or without parkinsonism, 600274 Pick disease, 172700 Supranuclear palsy, progressive, 601104 Supranuclear palsy, progressive atypical, 260540 {Parkinson disease, susceptibility to}, 168600 Tauopathy and r PARKINSON-DEMENTIA SYNDROME clinical presentation suggestive of cortico-basal/PSP syndrome Tags treatable
Green Green List (high evidence)	PANK2	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Expert Review Green Phenotypes Early Onset Complex Disease Dystonia pantothenate kinase-associated neurodegeneration Tags
Green Green List (high evidence)	PARK7	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Parkinson disease 7 autosomal recessive early-onset Parkinson Disease, Recessive Parkinson Disease 7, Autosomal Recessive Early-Onset Tags
Green Green List (high evidence)	PINK1	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Parkinson disease 6, early onset, 605909 Parkinson Disease, Recessive Parkinson Disease 6, Autosomal Recessive Early-Onset Tags
Green Green List (high evidence)	PLA2G6	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes Early Onset Complex Disease Infantile neuroaxonal dystrophy 1, 256600 Neurodegeneration with brain iron accumulation 2B, 610217 Parkinson disease 14, 612953 Tags
Green Green List (high evidence)	PRKN	2 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Illumina TruGenome Clinical Sequencing Services UKGTN Phenotypes Parkinson Disease, Juvenile Parkinson Disease 2, Autosomal Recessive Juvenile Tags
Green Green List (high evidence)	SGCE	1 review	MONOALLELIC, autosomal or pseudoautosomal, maternally imprinted (paternal allele expressed)	Sources Expert list Expert Review Green Phenotypes http://www.ncbi.nlm.nih.gov/books/NBK1155/ Tags
Green Green List (high evidence)	SLC6A3	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Review Green Radboud University Medical Center, Nijmegen Phenotypes {Nicotine dependence, protection against}, 188890 Parkinsonism -dystonia, infantile, 613135 {Nicotine dependence, protection against}, 188890 Parkinsonism-dystonia, infantile, 613135 Tags
Green Green List (high evidence)	SNCA	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Parkinson disease 4, 605543 Dementia, Lewy body, 127750 Parkinson disease 1, 168601 Parkinson Disease, Dominant PARKINSON DISEASE 1, AUTOSOMAL DOMINANT PARKINSON DISEASE 4, AUTOSOMAL DOMINANT DEMENTIA, LEWY BODY Autosomal dominant Parkinson's disease with alpha-synuclein rearrangements (PARK1/4) Tags
Green Green List (high evidence)	SPR	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Dopa-Responsive Dystonia Dystonia, dopa-responsive, due to sepiapterin reductase deficiency, 612716 paediatric form of dopa responsive dystonia Tags
Green Green List (high evidence)	TH	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Expert Review Green Phenotypes Segawa syndrome, recessive, 605407 paediatric form of dopa responsive dystonia Segawa syndrome Tags
Green Green List (high evidence)	THAP1	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Green Phenotypes Dystonia Dystonia 6, torsion, 602629 Tags
Green Green List (high evidence)	TOR1A	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Green Phenotypes Early-Onset Primary Dystonia Dystonia-1, torsion, 128100 Autosomal dominant or sporadic dystonia (DYT1) Tags
Green Green List (high evidence)	TUBB4A	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Green Phenotypes Dystonia ?Dystonia 4, torsion, autosomal dominant, 128101 hereditary whispering dysphonia Tags
Green Green List (high evidence)	VPS35	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Expert Review Green Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen UKGTN Phenotypes Parkinson disease 17, 614203 Parkinson Disease, Dominant PARKINSON DISEASE 17 PARK17 Tags
Green Green List (high evidence)	WDR45	1 review	X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)	Sources Expert Expert Review Green Phenotypes Dystonia beta-propeller protein-associated neurodegeneration Tags
Amber Amber List (moderate evidence)	GNAL	2 reviews 1 red	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert list Expert Review Amber Phenotypes Dystonia 25, 615073 Tags
Amber Amber List (moderate evidence)	HTRA2	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Illumina TruGenome Clinical Sequencing Services Radboud University Medical Center, Nijmegen Phenotypes Parkinson disease 13, 610297 Parkinson Disease, Dominant Tags
Amber Amber List (moderate evidence)	TAF1	1 review	X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)	Sources Expert Review Amber Radboud University Medical Center, Nijmegen Phenotypes Dystonia-Parkinsonism, X-linked, 314250 SVA retrotransposon insertion Dystonia-Parkinsonism, X-linked, 314250 Tags
Red Red List (low evidence)	C9orf72	2 reviews 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Eligibility statement prior genetic testing Expert Phenotypes (Hexanucleotideexpansion) clinical presentation suggestive of cortico-basal/PSP syndrome complex parkinsonism Tags
Red Red List (low evidence)	CSF1R	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Tags
Red Red List (low evidence)	DNAJC6	0 reviews	Not set	Sources Radboud University Medical Center, Nijmegen Phenotypes Parkinson disease 19, juvenile-onset, 615528 Tags
Red Red List (low evidence)	EIF4G1	0 reviews	Not set	Sources Radboud University Medical Center, Nijmegen Phenotypes Parkinsons disease 18, 614251 Tags
Red Red List (low evidence)	FTL	1 review 1 green	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Tags
Red Red List (low evidence)	GBA	0 reviews	Not set	Sources Radboud University Medical Center, Nijmegen Phenotypes Gaucher disease, type I, 230800 Gaucher disease, type II, 230900 Gaucher disease, type III, 231000 Gaucher disease, type IIIC, 231005 Gaucher disease, perinatal lethal, 608013 {Parkinson disease, late-onset, susceptibility to}, 168600 {Lewy body dementia, susceptibility to}, 127750 Tags
Red Red List (low evidence)	GIGYF2	0 reviews	Not set	Sources Radboud University Medical Center, Nijmegen Phenotypes Parkinson disease 11, 607688 Tags
Red Red List (low evidence)	GRN	0 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Eligibility statement prior genetic testing Expert Phenotypes clinical presentation suggestive of cortico-basal/PSP syndrome Tags
Red Red List (low evidence)	HTT	2 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Tags currently-ngs-unreportable nucleotide-repeat-expansion
Red Red List (low evidence)	IPPK	1 review	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Phenotypes Early Onset Complex Disease Tags
Red Red List (low evidence)	NR4A2	0 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Illumina TruGenome Clinical Sequencing Services Phenotypes Parkinson Disease, Dominant/Recessive Tags
Red Red List (low evidence)	PRKRA	0 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Phenotypes Early Onset Complex Disease Tags
Red Red List (low evidence)	RAB39B	0 reviews	X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)	Sources Expert Tags
Red Red List (low evidence)	SLC30A10	0 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Illumina TruGenome Clinical Sequencing Services Phenotypes Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, andChronic Liver Disease Dystonia/Parkinsonism, Hypermanganesemia, Polycythemia, and Chronic Liver Disease Tags
Red Red List (low evidence)	SLC41A1	0 reviews	Not set	Sources Radboud University Medical Center, Nijmegen Phenotypes Parkinson disease (Yan (2011) Int J Neurosci 121,632) Tags
Red Red List (low evidence)	SNCAIP	0 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Illumina TruGenome Clinical Sequencing Services Phenotypes Parkinson Disease, Dominant/Recessive Tags
Red Red List (low evidence)	SPG11	0 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Phenotypes Early Onset Complex Disease Tags
Red Red List (low evidence)	SYNJ1	0 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert Radboud University Medical Center, Nijmegen Phenotypes Early Onset Complex Disease Parkinson disease 20, early-onset, 615530 Tags
Red Red List (low evidence)	TBP	1 review	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Expert Radboud University Medical Center, Nijmegen Phenotypes Spinocerebellar ataxia 17, 607136 {Parkinson disease, susceptibility to}, 168600 Tags
Red Red List (low evidence)	UCHL1	0 reviews	MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown	Sources Illumina TruGenome Clinical Sequencing Services Phenotypes Parkinson Disease, Dominant Tags
Red Red List (low evidence)	VPS13A	0 reviews	BIALLELIC, autosomal or pseudoautosomal	Sources Expert list Phenotypes 200150 Tags

Complex Parkinsonism (includes pallido-pyramidal syndromes) (Version 0.55)

4 reviewers

48 Entities

33 reviewed, 24 green

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