Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Early onset or syndromic epilepsy v2.518 | FH | Arina Puzriakova Phenotypes for gene: FH were changed from Fumarase deficiency, 606812; Seizures to Fumarase deficiency, OMIM:606812 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v2.460 | CACNA1A | Arina Puzriakova Phenotypes for gene: CACNA1A were changed from Epileptic encephalopathy, early infantile, 42, 617106; Epilepsy and migraine; Absence epilepsy; Migraine, familial hemiplegic, 1, 141500; Familial hemiplegic migraine 1 (FHM) to Developmental and epileptic encephalopathy 42, OMIM:617106; Episodic ataxia, type 2, OMIM:108500; Migraine, familial hemiplegic, 1, with progressive cerebellar ataxia, OMIM:141500 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v2.434 | MED12 |
Eleanor Williams changed review comment from: Review of mode of inheritance shows that although in some families only males were affected, in 5 cases females with seizures as part of the phenotype were reported who had MED12 variants therefore a mode of inheritance of X-LINKED: hemizygous mutation in males, monoallelic mutations in females appears correct. Reports of males only affected: PMID: 17369503 - Schwartz et al 2007 - report 2 kindreds with males (7 total) affected with Lujan-Fryns syndrome and variants in MED12. Seizures were noted in 1 individual from 1 kindred. PMID: 23395478 - Vulto-van Silfhout et al 2013 - report 3 unrelated cases with males affected by Ohdo syndrome MKB type. In 2 families 2 males were affected, in the third 1 male. In all, missense changes in MED12 were detected. In family 2 a second segregating missense variant in the ATRX gene (linked to ATRX syndrome) but further investigation did not support a ATRX syndrome diagnosis. Intellectual disability was noted (1 mild, 1 moderate, 2 severe, 1 severity not noted) in all 5 individuals. Seizures were noted in 1. PMID: 32715471 - Rubin et al 2020 - report 1 family with three male siblings of with intellectual disability and characteristic facial and distal extremity anomalies with a novel missense variant in MED12. The diagnosis most closely matched Ohdo syndrome. Seizures are not reported. PMID: 17334363 - Risheg et al 2007 - report 6 families in with Opitz-Kaveggia syndrome (also known as FG syndrome) in with the same 2881C>T variant identified in MED12. Two of the families are stated to be from different ethnic groups. In all families only males were affected. Intellectual disability was present in all affected males (4 families) who survived long enough for developmental or cognitive assessment. Seizures were noted in 3 of the families (4/7 individuals). Marked skewed X inactivation was noted in female carriers in 3 families, moderate skewing in 1 family and absence of skewing in two families. Reports with females affected: PMID: 33244165 - Polla et al 2021 - report on assembled clinical and genetic data of 18 females with de novo variants in MED12. 11/18 have severe intellectual disability. Seizures were noted in 5. Analysis of X-inactivation status showed extreme skewing (>95%) in 10 indivduals, skewing (85%) in 1 individual and it was random XCI in 6 (3 with protein truncating variants, 3 with missense). The androgen receptor alleles were non-informative for 1 person. PMID: 34079076 - Riccardi et al 2021 - report an additional 4 female patients that carry de novo missense variants in MED12. All four patients had an intellectual disability, though it was severe only in one case. No seizures were noted.; to: Review of mode of inheritance shows that although in some families only males were affected, in 5 cases females with seizures as part of the phenotype were reported who had MED12 variants therefore a mode of inheritance of X-LINKED: hemizygous mutation in males, monoallelic mutations in females appears correct although consideration should be given to the carrier implications for the predominantly male-only phenotypes associated with this gene. Reports of males only affected: PMID: 17369503 - Schwartz et al 2007 - report 2 kindreds with males (7 total) affected with Lujan-Fryns syndrome and variants in MED12. Seizures were noted in 1 individual from 1 kindred. PMID: 23395478 - Vulto-van Silfhout et al 2013 - report 3 unrelated cases with males affected by Ohdo syndrome MKB type. In 2 families 2 males were affected, in the third 1 male. In all, missense changes in MED12 were detected. In family 2 a second segregating missense variant in the ATRX gene (linked to ATRX syndrome) but further investigation did not support a ATRX syndrome diagnosis. Intellectual disability was noted (1 mild, 1 moderate, 2 severe, 1 severity not noted) in all 5 individuals. Seizures were noted in 1. PMID: 32715471 - Rubin et al 2020 - report 1 family with three male siblings of with intellectual disability and characteristic facial and distal extremity anomalies with a novel missense variant in MED12. The diagnosis most closely matched Ohdo syndrome. Seizures are not reported. PMID: 17334363 - Risheg et al 2007 - report 6 families in with Opitz-Kaveggia syndrome (also known as FG syndrome) in with the same 2881C>T variant identified in MED12. Two of the families are stated to be from different ethnic groups. In all families only males were affected. Intellectual disability was present in all affected males (4 families) who survived long enough for developmental or cognitive assessment. Seizures were noted in 3 of the families (4/7 individuals). Marked skewed X inactivation was noted in female carriers in 3 families, moderate skewing in 1 family and absence of skewing in two families. Reports with females affected: PMID: 33244165 - Polla et al 2021 - report on assembled clinical and genetic data of 18 females with de novo variants in MED12. 11/18 have severe intellectual disability. Seizures were noted in 5. Analysis of X-inactivation status showed extreme skewing (>95%) in 10 indivduals, skewing (85%) in 1 individual and it was random XCI in 6 (3 with protein truncating variants, 3 with missense). The androgen receptor alleles were non-informative for 1 person. PMID: 34079076 - Riccardi et al 2021 - report an additional 4 female patients that carry de novo missense variants in MED12. All four patients had an intellectual disability, though it was severe only in one case. No seizures were noted. |
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Early onset or syndromic epilepsy v2.431 | MED12 |
Eleanor Williams changed review comment from: Review of mode of inheritance shows that although in some families only males were affected, females were also reported in 5 cases seizures with MED12 variants therefore a mode of inheritance of X-LINKED: hemizygous mutation in males, monoallelic mutations in females appears correct. Reports of males only affected: PMID: 17369503 - Schwartz et al 2007 - report 2 kindreds with males (7 total) affected with Lujan-Fryns syndrome and variants in MED12. Seizures were noted in 1 individual from 1 kindred. PMID: 23395478 - Vulto-van Silfhout et al 2013 - report 3 unrelated cases with males affected by Ohdo syndrome MKB type. In 2 families 2 males were affected, in the third 1 male. In all, missense changes in MED12 were detected. In family 2 a second segregating missense variant in the ATRX gene (linked to ATRX syndrome) but further investigation did not support a ATRX syndrome diagnosis. Intellectual disability was noted (1 mild, 1 moderate, 2 severe, 1 severity not noted) in all 5 individuals. Seizures were noted in 1. PMID: 32715471 - Rubin et al 2020 - report 1 family with three male siblings of with intellectual disability and characteristic facial and distal extremity anomalies with a novel missense variant in MED12. The diagnosis most closely matched Ohdo syndrome. Seizures are not reported. PMID: 17334363 - Risheg et al 2007 - report 6 families in with Opitz-Kaveggia syndrome (also known as FG syndrome) in with the same 2881C>T variant identified in MED12. Two of the families are stated to be from different ethnic groups. In all families only males were affected. Intellectual disability was present in all affected males (4 families) who survived long enough for developmental or cognitive assessment. Seizures were noted in 3 of the families (4/7 individuals). Marked skewed X inactivation was noted in female carriers in 3 families, moderate skewing in 1 family and absence of skewing in two families. Reports with females affected: PMID: 33244165 - Polla et al 2021 - report on assembled clinical and genetic data of 18 females with de novo variants in MED12. 11/18 have severe intellectual disability. Seizures were noted in 5. Analysis of X-inactivation status showed extreme skewing (>95%) in 10 indivduals, skewing (85%) in 1 individual and it was random XCI in 6 (3 with protein truncating variants, 3 with missense). The androgen receptor alleles were non-informative for 1 person. PMID: 34079076 - Riccardi et al 2021 - report an additional 4 female patients that carry de novo missense variants in MED12. All four patients had an intellectual disability, though it was severe only in one case. No seizures were noted.; to: Review of mode of inheritance shows that although in some families only males were affected, in 5 cases females with seizures as part of the phenotype were reported who had MED12 variants therefore a mode of inheritance of X-LINKED: hemizygous mutation in males, monoallelic mutations in females appears correct. Reports of males only affected: PMID: 17369503 - Schwartz et al 2007 - report 2 kindreds with males (7 total) affected with Lujan-Fryns syndrome and variants in MED12. Seizures were noted in 1 individual from 1 kindred. PMID: 23395478 - Vulto-van Silfhout et al 2013 - report 3 unrelated cases with males affected by Ohdo syndrome MKB type. In 2 families 2 males were affected, in the third 1 male. In all, missense changes in MED12 were detected. In family 2 a second segregating missense variant in the ATRX gene (linked to ATRX syndrome) but further investigation did not support a ATRX syndrome diagnosis. Intellectual disability was noted (1 mild, 1 moderate, 2 severe, 1 severity not noted) in all 5 individuals. Seizures were noted in 1. PMID: 32715471 - Rubin et al 2020 - report 1 family with three male siblings of with intellectual disability and characteristic facial and distal extremity anomalies with a novel missense variant in MED12. The diagnosis most closely matched Ohdo syndrome. Seizures are not reported. PMID: 17334363 - Risheg et al 2007 - report 6 families in with Opitz-Kaveggia syndrome (also known as FG syndrome) in with the same 2881C>T variant identified in MED12. Two of the families are stated to be from different ethnic groups. In all families only males were affected. Intellectual disability was present in all affected males (4 families) who survived long enough for developmental or cognitive assessment. Seizures were noted in 3 of the families (4/7 individuals). Marked skewed X inactivation was noted in female carriers in 3 families, moderate skewing in 1 family and absence of skewing in two families. Reports with females affected: PMID: 33244165 - Polla et al 2021 - report on assembled clinical and genetic data of 18 females with de novo variants in MED12. 11/18 have severe intellectual disability. Seizures were noted in 5. Analysis of X-inactivation status showed extreme skewing (>95%) in 10 indivduals, skewing (85%) in 1 individual and it was random XCI in 6 (3 with protein truncating variants, 3 with missense). The androgen receptor alleles were non-informative for 1 person. PMID: 34079076 - Riccardi et al 2021 - report an additional 4 female patients that carry de novo missense variants in MED12. All four patients had an intellectual disability, though it was severe only in one case. No seizures were noted. |
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Early onset or syndromic epilepsy v2.431 | MED12 |
Eleanor Williams changed review comment from: Review of mode of inheritance shows that although in some families only males were affected, females were also reported in 5 cases with MED12 variants therefore a mode of inheritance of X-LINKED: hemizygous mutation in males, monoallelic mutations in females appears correct. Reports of males only affected: PMID: 17369503 - Schwartz et al 2007 - report 2 kindreds with males (7 total) affected with Lujan-Fryns syndrome and variants in MED12. Seizures were noted in 1 individual from 1 kindred. PMID: 23395478 - Vulto-van Silfhout et al 2013 - report 3 unrelated cases with males affected by Ohdo syndrome MKB type. In 2 families 2 males were affected, in the third 1 male. In all, missense changes in MED12 were detected. In family 2 a second segregating missense variant in the ATRX gene (linked to ATRX syndrome) but further investigation did not support a ATRX syndrome diagnosis. Intellectual disability was noted (1 mild, 1 moderate, 2 severe, 1 severity not noted) in all 5 individuals. Seizures were noted in 1. PMID: 32715471 - Rubin et al 2020 - report 1 family with three male siblings of with intellectual disability and characteristic facial and distal extremity anomalies with a novel missense variant in MED12. The diagnosis most closely matched Ohdo syndrome. Seizures are not reported. PMID: 17334363 - Risheg et al 2007 - report 6 families in with Opitz-Kaveggia syndrome (also known as FG syndrome) in with the same 2881C>T variant identified in MED12. Two of the families are stated to be from different ethnic groups. In all families only males were affected. Intellectual disability was present in all affected males (4 families) who survived long enough for developmental or cognitive assessment. Seizures were noted in 3 of the families (4/7 individuals). Marked skewed X inactivation was noted in female carriers in 3 families, moderate skewing in 1 family and absence of skewing in two families. Reports with females affected: PMID: 33244165 - Polla et al 2021 - report on assembled clinical and genetic data of 18 females with de novo variants in MED12. 11/18 have severe intellectual disability. Seizures were noted in 5. Analysis of X-inactivation status showed extreme skewing (>95%) in 10 indivduals, skewing (85%) in 1 individual and it was random XCI in 6 (3 with protein truncating variants, 3 with missense). The androgen receptor alleles were non-informative for 1 person. PMID: 34079076 - Riccardi et al 2021 - report an additional 4 female patients that carry de novo missense variants in MED12. All four patients had an intellectual disability, though it was severe only in one case. No seizures were noted.; to: Review of mode of inheritance shows that although in some families only males were affected, females were also reported in 5 cases seizures with MED12 variants therefore a mode of inheritance of X-LINKED: hemizygous mutation in males, monoallelic mutations in females appears correct. Reports of males only affected: PMID: 17369503 - Schwartz et al 2007 - report 2 kindreds with males (7 total) affected with Lujan-Fryns syndrome and variants in MED12. Seizures were noted in 1 individual from 1 kindred. PMID: 23395478 - Vulto-van Silfhout et al 2013 - report 3 unrelated cases with males affected by Ohdo syndrome MKB type. In 2 families 2 males were affected, in the third 1 male. In all, missense changes in MED12 were detected. In family 2 a second segregating missense variant in the ATRX gene (linked to ATRX syndrome) but further investigation did not support a ATRX syndrome diagnosis. Intellectual disability was noted (1 mild, 1 moderate, 2 severe, 1 severity not noted) in all 5 individuals. Seizures were noted in 1. PMID: 32715471 - Rubin et al 2020 - report 1 family with three male siblings of with intellectual disability and characteristic facial and distal extremity anomalies with a novel missense variant in MED12. The diagnosis most closely matched Ohdo syndrome. Seizures are not reported. PMID: 17334363 - Risheg et al 2007 - report 6 families in with Opitz-Kaveggia syndrome (also known as FG syndrome) in with the same 2881C>T variant identified in MED12. Two of the families are stated to be from different ethnic groups. In all families only males were affected. Intellectual disability was present in all affected males (4 families) who survived long enough for developmental or cognitive assessment. Seizures were noted in 3 of the families (4/7 individuals). Marked skewed X inactivation was noted in female carriers in 3 families, moderate skewing in 1 family and absence of skewing in two families. Reports with females affected: PMID: 33244165 - Polla et al 2021 - report on assembled clinical and genetic data of 18 females with de novo variants in MED12. 11/18 have severe intellectual disability. Seizures were noted in 5. Analysis of X-inactivation status showed extreme skewing (>95%) in 10 indivduals, skewing (85%) in 1 individual and it was random XCI in 6 (3 with protein truncating variants, 3 with missense). The androgen receptor alleles were non-informative for 1 person. PMID: 34079076 - Riccardi et al 2021 - report an additional 4 female patients that carry de novo missense variants in MED12. All four patients had an intellectual disability, though it was severe only in one case. No seizures were noted. |
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Early onset or syndromic epilepsy v2.431 | MED12 |
Eleanor Williams changed review comment from: Review of mode of inheritance shows that although in some families only males were affected, females were also reported in 5 cases with MED12 variants therefore a mode of inheritance of X-LINKED: hemizygous mutation in males, monoallelic mutations in females appears correct. Reports of males only affected: PMID: 17369503 - Schwartz et al 2007 - report 2 kindreds with males (7 total) affected with Lujan-Fryns syndrome and variants in MED12. Seizures were noted in 1 individual from 1 kindred. PMID: 23395478 - Vulto-van Silfhout et al 2013 - report 3 unrelated cases with males affected by Ohdo syndrome MKB type. In 2 families 2 males were affected, in the third 1 male. In all, missense changes in MED12 were detected. In family 2 a second segregating missense variant in the ATRX gene (linked to ATRX syndrome) but further investigation did not support a ATRX syndrome diagnosis. Intellectual disability was noted (1 mild, 1 moderate, 2 severe, 1 severity not noted) in all 5 individuals. Seizures were noted in 1. PMID: 32715471 - Rubin et al 2020 - report 1 family with three male siblings of with intellectual disability and characteristic facial and distal extremity anomalies with a novel missense variant in MED12. The diagnosis most closely matched Ohdo syndrome. Seizures are not reported. PMID: 17334363 - Risheg et al 2007 - report 6 families in with Opitz-Kaveggia syndrome (also known as FG syndrome) in with the same 2881C>T variant identified in MED12. In all families only males were affected. Intellectual disability was present in all affected males (4 families) who survived long enough for developmental or cognitive assessment. Seizures were noted in 3 of the families (4/7 individuals). Marked skewed X inactivation was noted in female carriers in 3 families, moderate skewing in 1 family and absence of skewing in two families. Reports with females affected: PMID: 33244165 - Polla et al 2021 - report on assembled clinical and genetic data of 18 females with de novo variants in MED12. 11/18 have severe intellectual disability. Seizures were noted in 5. Analysis of X-inactivation status showed extreme skewing (>95%) in 10 indivduals, skewing (85%) in 1 individual and it was random XCI in 6 (3 with protein truncating variants, 3 with missense). The androgen receptor alleles were non-informative for 1 person. PMID: 34079076 - Riccardi et al 2021 - report an additional 4 female patients that carry de novo missense variants in MED12. All four patients had an intellectual disability, though it was severe only in one case. No seizures were noted.; to: Review of mode of inheritance shows that although in some families only males were affected, females were also reported in 5 cases with MED12 variants therefore a mode of inheritance of X-LINKED: hemizygous mutation in males, monoallelic mutations in females appears correct. Reports of males only affected: PMID: 17369503 - Schwartz et al 2007 - report 2 kindreds with males (7 total) affected with Lujan-Fryns syndrome and variants in MED12. Seizures were noted in 1 individual from 1 kindred. PMID: 23395478 - Vulto-van Silfhout et al 2013 - report 3 unrelated cases with males affected by Ohdo syndrome MKB type. In 2 families 2 males were affected, in the third 1 male. In all, missense changes in MED12 were detected. In family 2 a second segregating missense variant in the ATRX gene (linked to ATRX syndrome) but further investigation did not support a ATRX syndrome diagnosis. Intellectual disability was noted (1 mild, 1 moderate, 2 severe, 1 severity not noted) in all 5 individuals. Seizures were noted in 1. PMID: 32715471 - Rubin et al 2020 - report 1 family with three male siblings of with intellectual disability and characteristic facial and distal extremity anomalies with a novel missense variant in MED12. The diagnosis most closely matched Ohdo syndrome. Seizures are not reported. PMID: 17334363 - Risheg et al 2007 - report 6 families in with Opitz-Kaveggia syndrome (also known as FG syndrome) in with the same 2881C>T variant identified in MED12. Two of the families are stated to be from different ethnic groups. In all families only males were affected. Intellectual disability was present in all affected males (4 families) who survived long enough for developmental or cognitive assessment. Seizures were noted in 3 of the families (4/7 individuals). Marked skewed X inactivation was noted in female carriers in 3 families, moderate skewing in 1 family and absence of skewing in two families. Reports with females affected: PMID: 33244165 - Polla et al 2021 - report on assembled clinical and genetic data of 18 females with de novo variants in MED12. 11/18 have severe intellectual disability. Seizures were noted in 5. Analysis of X-inactivation status showed extreme skewing (>95%) in 10 indivduals, skewing (85%) in 1 individual and it was random XCI in 6 (3 with protein truncating variants, 3 with missense). The androgen receptor alleles were non-informative for 1 person. PMID: 34079076 - Riccardi et al 2021 - report an additional 4 female patients that carry de novo missense variants in MED12. All four patients had an intellectual disability, though it was severe only in one case. No seizures were noted. |
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Early onset or syndromic epilepsy v1.441 | FH | Rebecca Foulger Classified gene: FH as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.441 | FH | Rebecca Foulger Gene: fh has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.440 | FH | Rebecca Foulger commented on gene: FH: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call 22nd November 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that there is insufficient evidence to rate this gene Green. Better tested through the metabolic panel. Demoted from Green to Amber. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.233 | EFHC1 | Rebecca Foulger Marked gene: EFHC1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.233 | EFHC1 | Rebecca Foulger Gene: efhc1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.222 | EFHC1 | Rebecca Foulger changed review comment from: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that this gene should remain as Amber: EFHC1 may be a susceptibility locus. Currently insufficient evidence to support a monogenic association with epilepsy.; to: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019 for Clinical Indication R59 Early onset or syndromic epilepsy: Agreed that this gene should remain as Amber: EFHC1 may be a susceptibility locus. Currently insufficient evidence to support a monogenic association with epilepsy. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.215 | EFHC1 | Rebecca Foulger commented on gene: EFHC1: As discussed with members of the GMS Neurology Specialist Test Group on the Webex call Thursday 8th August 2019: Agreed that this gene should remain as Amber: EFHC1 may be a susceptibility locus. Currently insufficient evidence to support a monogenic association with epilepsy. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.191 | EFHC1 | Rebecca Foulger Source Wessex and West Midlands GLH was added to EFHC1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.191 | FH | Rebecca Foulger Source Wessex and West Midlands GLH was added to FH. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.190 | EFHC1 | Rebecca Foulger Source NHS GMS was added to EFHC1. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.190 | FH | Rebecca Foulger Source NHS GMS was added to FH. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.189 | EFHC1 | Rebecca Foulger edited their review of gene: EFHC1: Added comment: Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: Alison Callaway and John Taylor. Suggested gene rating: Green. ; Changed rating: AMBER | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.189 | FH | Rebecca Foulger reviewed gene: FH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.188 | EFHC1 | Tracy Lester reviewed gene: EFHC1: Rating: GREEN; Mode of pathogenicity: ; Publications: 19901254; Phenotypes: {Epilepsy, juvenile absence, susceptibility to, 1}, 607631 , {Myoclonic epilepsy, juvenile, susceptibility to, 1}, 254770; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.188 | FH | Tracy Lester reviewed gene: FH: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Fumarase deficiency, 606812, Leiomyomatosis and renal cell cancer, 150800; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.86 | EFHC1 | Rebecca Foulger Publications for gene: EFHC1 were set to 17159113; 18505993; 15258581; 19147686; 28370826 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.85 | EFHC1 | Rebecca Foulger commented on gene: EFHC1: PMID:29750216: Thounaojam et al., 2017 studied 63 Indian patients from 63 independent families with Juvenile myoclonic epilepsy (JME) and found 4 heterozygous coding variants (R221C, R260Q, R294H and R244STOP) and 1 homozygous and one heterozygous coding variant (R159W, which is considered a polymorphism). Lack of family samples meant the mode of inheritance couldn't be followed up. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.85 | EFHC1 | Rebecca Foulger commented on gene: EFHC1: PMID:31056551: Heyne et al., 2019 performed a large-scale analysis of previously-sequenced variants in individuals with a 'neurodevelopmental disorder with epilepsy. They show that EFHC1 showed equal frequencies of ultra-rare variants in cases and controls supporting the existing evidence that EFHC1 may not be truly associated with epilepsy. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.85 | EFHC1 | Rebecca Foulger changed review comment from: PMID:28370826. Raju et al., 2017 examine 480 Juvenile myoclonic epilepsy patients from India, and identified 13 variants (11 of which were novel, 10 of which are predicted to be pathogenic) in 28 JME patients. They were absent or uncommon among controls. Patients with family histories of progressive myoclonic epilepsy (PME) were not included in the study. The authors submitted their variants to LOVD, including 14 polymorphisms that were common in controls and databases (https://databases.lovd.nl/shared/variants/EFHC1/unique).; to: PMID:28370826. Raju et al., 2017 examine 480 Juvenile myoclonic epilepsy patients from India, and identified 13 variants (11 of which were novel, 10 of which are predicted to be pathogenic) in 28 JME patients. They were absent or uncommon among controls. All variants were missense. Patients with family histories of progressive myoclonic epilepsy (PME) were not included in the study. The authors submitted their variants to LOVD, including 14 polymorphisms that were common in controls and databases (https://databases.lovd.nl/shared/variants/EFHC1/unique). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.85 | EFHC1 | Rebecca Foulger commented on gene: EFHC1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.85 | EFHC1 | Rebecca Foulger Publications for gene: EFHC1 were set to 17159113; 18505993; 15258581; 19147686 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.83 | CUL4B | Rebecca Foulger commented on gene: CUL4B: PMID:25385192: Vulto-van Silfhout et al, 2015 identified CUL4B variants in 8/407 families with X-linked mental retardation. Plus CUL4B variants in an additional 3 patients (2 families) with malformations of cortical development. Ten different variants were identified in the 10 families (5 truncating, 2 splice, 1 in-frame deletion, 1 in-frame duplication, 1 missense). Across the 10 families with CUL4B variants, 7/22 (32%) of the individuals had seizures, though the phenotype was not always consistent between family members: In both family 1 (N151) and family 5 (D173), 1 of 3 individuals had seizures. The authors note that previously 17/30 (57%) of individuals with CUL4B variants were reported to have seizures. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.48 | ATP1A2 | Rebecca Foulger Added comment: Comment on list classification: Updated rating from Amber to Green after discussion with Sarah Leigh; Sufficient cases from PMIDs:28058944, 18028407 and 12953268 of patients with familial hemiplegic migraine (FHM) also exhibiting seizures; PMID:28058944 (Prontera et al., 2018) calculate a co-occurrence of ~30%. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.46 | CACNA1A | Rebecca Foulger Phenotypes for gene: CACNA1A were changed from Epileptic encephalopathy, early infantile, 42 617106 to Epileptic encephalopathy, early infantile, 42, 617106; Epilepsy and migraine; Absence epilepsy; Migraine, familial hemiplegic, 1, 141500; Familial hemiplegic migraine 1 (FHM) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.44 | ATP1A2 | Rebecca Foulger commented on gene: ATP1A2: Vanmolkot et al., 2003 (PMID:12953268) describe novel variants in ATP1A2 in two families with FHM. The M731T mutation was found in a family with pure FHM. The R689Q variant was identified in a family in which FHM and benign familial infantile convulsions partially cosegregate; all available affected family members with FHM, benign familial infantile convulsions, or both, carried the ATP1A2 mutation. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v1.42 | ATP1A2 | Rebecca Foulger Added comment: Comment on publications: PMID:9579893 (Terwindt et al., 1997) studied a large Dutch-Canadian family in which familial hemiplegic migraine (FHM) and a benign familial infantile epileptic syndrome concur and partially cosegregate. The genetic basis of the conditions was not finalised. Note that ATP1A2 is on chromosome 1q23.2. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.874 | EFHC1 | Sarah Leigh Marked gene: EFHC1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.874 | EFHC1 | Sarah Leigh Gene: efhc1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.874 | EFHC1 | Sarah Leigh Classified gene: EFHC1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.874 | EFHC1 | Sarah Leigh Added comment: Comment on list classification: As this gene is associated with susceptibility to juvenile absence epilepsy (MIM 607631) and juvenile myoclonic epilepsy 1 (MIM 254770), EFHC1 has been rated at amber in consultation with Arianna Tucci (GEL Clinical Fellow). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.874 | EFHC1 | Sarah Leigh Gene: efhc1 has been classified as Amber List (Moderate Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.851 | FH | Louise Daugherty Marked gene: FH as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.851 | FH | Louise Daugherty Gene: fh has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.851 | FH | Louise Daugherty Classified gene: FH as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.851 | FH | Louise Daugherty Added comment: Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.851 | FH | Louise Daugherty Gene: fh has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.850 | FH | Louise Daugherty Publications for gene: FH were set to 2314594; 10805328; 10805328; 20301679 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.847 | FH | Louise Daugherty edited their review of gene: FH: Added comment: From GeneReview PMID: 20301679. Fumarate hydratase deficiency results in severe neonatal and early infantile encephalopathy that is characterized by poor feeding, failure to thrive, hypotonia, lethargy, and seizures. Epileptic seizures are common (40%-80%), although age of onset and seizure type are variable (PMID:10805328, PMID:20549362). Infantile spasms (epileptic spasms) accompanied by hypsarrhythmia on EEG have been reported (PMID:15221078, PMID:16151915).; Changed rating: GREEN | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.845 | FH | Louise Daugherty Added comment: Comment on publications: Added publications to support upgrading of the gene to Green | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.845 | FH | Louise Daugherty Publications for gene: FH were set to | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.844 | FH | Louise Daugherty Added comment: Comment on mode of inheritance: Added MOI from external clinical review and publications | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.844 | FH | Louise Daugherty Mode of inheritance for gene: FH was changed from to BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.843 | FH | Louise Daugherty Added comment: Comment on phenotypes: Added phenotype suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy v0.843 | FH | Louise Daugherty Phenotypes for gene: FH were changed from to Fumarase deficiency, 606812; Seizures | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy | FH | Zornitza Stark reviewed gene: FH | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy | EFHC1 | Sarah Leigh classified EFHC1 as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy | FH | Sarah Leigh Added gene to panel | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy | EFHC1 | Sarah Leigh classified EFHC1 as Amber List (moderate evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Early onset or syndromic epilepsy | EFHC1 | Sarah Leigh classified EFHC1 as Amber List (moderate evidence) |