Genetic Epilepsy

Gene: SCN1A

DEFINITIVE by ClinGen Epilepsy GCEP for generalized epilepsy with febrile seizures plus on 06/09/2019 - https://search.clinicalgenome.org/CCID:006064

DEFINITIVE by ClinGen Epilepsy GCEP for Dravet Syndrome on 20/08/2019 - https://search.clinicalgenome.org/CCID:006065

STRONG by ClinGen Epilepsy GCEP for developmental and epileptic encephalopathy on 25/10/2019 - https://search.clinicalgenome.org/CCID:006063

MODERATE by ClinGen Epilepsy GCEP for familial hemiplegic migraine on 14/09/2021 - https://search.clinicalgenome.org/CCID:006066

Created: 22 Apr 2024, 1:39 a.m. | Last Modified: 22 Apr 2024, 1:39 a.m.

Panel Version: 0.2599

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
generalized epilepsy with febrile seizures plus (MONDO:0018214); Dravet syndrome (MONDO:0100135); developmental and epileptic encephalopathy (MONDO:0100062); familial hemiplegic migraine (MONDO:0000700)

I don't know

Note SCN1A is a well-established cause of Dravet syndrome, MIM# 607208
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PMID: 32928894 (2020) - De novo missense variants in SCN1A (p.Leu893Phe, p.Ala989Thr, p.Ile236Thr) were identified in three unrelated patients with AMC which was diagnosed from the second trimester of pregnancy. One patient developed intractable epilepsy from birth and died at 21 days, while the other two pregnancies were terminated. No functional studies of the variants or patient cells were performed.

To my knowledge, this is currently the only publication reporting an association between SCN1A variants and AMC.

Created: 2 Oct 2020, 4:13 p.m. | Last Modified: 2 Oct 2020, 4:13 p.m.

Panel Version: 0.4742

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
Arthrogryposis multiplex congenita

Publications

• 32928894

Green List (high evidence)

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epilepsy, generalized, with febrile seizures plus, type 2 604403; Epileptic encephalopathy, early infantile, 6 (Dravet syndrome) 607208; Developmental and epileptic encephalopathy 6B, non-Dravet, MIM# 619317; Febrile seizures, familial, 3A 604403

Green List (high evidence)

> 3 de novo mutation carriers with evidence of low-level parental mosaicism
Mutations in pore regions result in more severe phenotypes

Created: 20 Apr 2020, 2:59 a.m. | Last Modified: 20 Apr 2020, 2:59 a.m.

Panel Version: 0.2362

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Dravet Syndrome; Genetic Epilepsy Febrile Seizures plus (GEFS+) Syndrome; Febrile seizures

Publications

• PMID: 30368457
• 12754708
• 25754450

Variants in this GENE are reported as part of current diagnostic practice