Early onset or syndromic epilepsy

Gene: GABRB2

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)

AD infantile or early childhood epileptic encephalopahy 2 (IECEE2) - seizure type and severity may vary and may be intractable. Srivastava et al 2014 - 12 year old Spanish girl - developed febrile seizures at 9 months - eventualy developed non-febrile tonic-clonic and subtle seizures - de novo het missense variant. Ishii et al, 2017 - 2 year old boy with generalised tonic-clonic seizures - de novo het missense variant - in vitro functionsal studies done. Hamdan et al, 2017 - 10 unrelated patients - all but 1 had seizures - onset occured between 6 months and 6 years - all types. De novo het missense variants in all.

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

Panel Version: 1.188

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epileptic encephalopathy, infantile or early childhood, 617829

Publications

• 29053855

Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease association

Created: 22 Nov 2018, 10:47 a.m.

Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green. Hamdan et al. (2017) PMID 29100083 reported 3 unrelated cases with de novo missense variants in GABRB2 who had developmental and epileptic encephalopathy. Srivastava et al. (2014) PMID 25124326 . Ishii et al. (2017) PMID: 27789573 describes a 12-year old girl with intellectual disability and epilepsy due to another de novo missense variant in GABRB2 epileptic seizures. Ishii et al. (2017) PMID 27789573 describes a patient with early myoclonic encephalopathy and severe psycomotor delay, due to a de novo heterozygous missense mutation in GABRB2.

Created: 22 Nov 2018, 10:44 a.m.

Comment on phenotypes: Added phenotypes suggested from expert review that indicate relevance to inclusion on the Genetic Epilepsy Syndromes panel

Created: 22 Nov 2018, 10:15 a.m.

Green List (high evidence)

Multiple patients from unrelated families reported with de novo variants in this EE gene.

Created: 14 Aug 2018, 12:20 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Epileptic encephalopathy, infantile or early childhood, 2, MIM#617829

Publications

• 29100083, 27789573, 25124326

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