Early onset or syndromic epilepsy

Gene: SCN1B

I don't know

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: John Taylor and Helen Lord. Suggested gene rating: Green.

Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.

Panel Version: 1.189

Green List (high evidence)

AR EIEE52, AD generalised epilepsy with febrile seizures and also assoc with atrial fibrillation, cardiac conduction defect and Brugada syndrome. AD epilepsy - Wallace et al 1998 and 2002 - 2 Australian families with this variant. First family large 6 generation family where 42 individuals had a history of seizures. Did see unaffected carriers suggests reduced penetrance . AR epilepsy - Patino et al, 2009 - boy born of consang Moroccan parents - hom missense variant, in vitro functional studies showed that the mutant protein was poorly expressed at the cell surface, despite robist intracellular expression, consistent with a tracking defect to the membrane. Carrier parents did not have seizures. Ogiwara et al, 2012 - Japanese man with unrelated parents hom for a missense variant. Functional work not done. 17 different variants reported on HGMD Pro in association with epilepsy/seizures and number of cases on OMIM.

Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.

Panel Version: 1.188

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Atrial fibrillation, familial,615377; Brugada syndrome,612838; Cardiac conduction defect, nonspecific,612838; Epilepsy, generalized, with febrile seizures plus, type 1,604233; Epileptic encephalopathy, early infantile, 52,617350

Publications

• 23148524
• 19710327
• 17020904

Comment on mode of inheritance: Epilepsy, generalized, with febrile seizures plus, type 1 604233 monoallelic not imprinted;
Epileptic encephalopathy, early infantile, 52 617350 biallelic

Created: 4 Apr 2018, 3:02 p.m.

Green List (high evidence)

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

Phenotypes
Epilepsy, generalized, with febrile seizures plus, type 1

Publications

• Wallace et al (2002) Neurology 58: 1426-1429

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

Green List (high evidence)

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

Phenotypes
Epilepsy, generalized, with febrile seizures plus, type 1

Publications

• Wallace et al (2002) Neurology 58: 1426-1429

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

Green List (high evidence)

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

Phenotypes
Epilepsy, generalized, with febrile seizures plus, type 1

Publications

• Wallace et al (2002) Neurology 58: 1426-1429

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

Green List (high evidence)

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

Phenotypes
Epilepsy, generalized, with febrile seizures plus, type 1

Publications

• Wallace et al (2002) Neurology 58: 1426-1429

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

Comment on list classification: Evidence of pathogenicity exists for M_001037.4(SCN1B):c.363C>G (p.Cys121Trp); few if any other variants have sufficient evidence for pathogenicity currently

Created: 8 May 2016, 7:11 p.m.

Comment when marking as ready: Confirmed DD gene and all 4 reviewers agree this should be green. Mode of inheritance and loss-of-function mechanism confirmed.

Created: 21 Jan 2016, 11:52 a.m.

Comment on mode of inheritance: Confirmed and not on imprinted gene list.

Created: 21 Jan 2016, 11:51 a.m.