Early onset or syndromic epilepsy
Gene: GFAP
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
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
Comment on list classification: Changed from Amber to Green. Appropriate phenotype, sufficient cases, and external review comment all support gene-disease associationCreated: 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.
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
Source Wessex and West Midlands GLH was added to GFAP.
Source NHS GMS was added to GFAP.
Zornitza Stark: Seizures are part of the pheno
Gene: gfap has been classified as Green List (High Evidence).
Gene: gfap has been classified as Green List (High Evidence).
Mode of inheritance for gene: GFAP was changed from to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes for gene: GFAP were changed from to Alexander disease, 203450; seizures
Publications for gene: GFAP were set to
Expert Review Amber was added to GFAP. Panel: Genetic Epilepsy Syndromes
GFAP was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
GFAP was created by Sarah Leigh