Early onset or syndromic epilepsy

Gene: GFAP

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 Alexander disease - 3 forms - the younger patients tend to present with seizures, megalencephaly, dev delay and spasticity. Gorospe et al, 2002 - 12 genetically confirmed cases of Alexander disease - 7/12 infant onset - seizures most common presenting sign. Bassuk et al, 2003 - infant with Alexander - seizures developed on day 23. Li et al, 2005 - detailed clinical features of 44 patients with Alexander disease - of 26 with infantile onset - 92% had seizures and of the 15 with juvenille onset - 27% had seizures.

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
Alexander disease, 203450

Publications

• 11587071
• 22496548

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

Created: 20 Nov 2018, 4:14 p.m.

Comment on publications: Added publications suggested from external expert review to support upgrading of the gene to Green. From OMIM PMID: 12034785 Gorospe et al. (2002) reported 12 genetically confirmed cases of Alexander disease. Seven of the 12 had onset in infancy (range 2-18 months), with seizures being the most common presenting sign, followed by failure to thrive and delayed motor development.

Created: 20 Nov 2018, 4:11 p.m.

Green List (high evidence)

Seizures are part of the phenotype of this metabolic disorder.

Created: 14 Aug 2018, 9:38 a.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Alexander disease, MIM#203450

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