Early onset or syndromic epilepsy

Gene: HTRA2

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 3-methylglutaconic aciduria type VIII. Metabolic disroder resulting in death in infancy. Features include hypotonia, abnormal movements, respiratory insufficiency with apneic episodes and lack of developmental progress often with seizures. Mandel et al, 2016 - 3 sibs born of consang parents of Druze origin - all had intractable seizures and died in infancy. Unrelated boy, consang parents of AJ origin - refractory monoclonic seizures and died at 5 months of age. Hom mutations identified - segregated with disease. Western blot analysis showed complete absence of protein. Olahava et al, 2017 - 5 infants from 2 unrelated consang famillies (Pakistani and Mexican) seizures more variable feature (Pakistani family 2 aff died at 2 months and 3 weeks respectively and also 2 other infants who died in early infancy with similar symptoms. Mexican family 2/3 had seizures - all died 2 at 3 months and 1 at 4 months). Hom mutations identifed.

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

Panel Version: 1.188

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 27696117
• 27208207

Green List (high evidence)

Associated with phenotype in OMIM and as a possible G2P. At least 4 homozygous variants reported in 4 unrelated ethnically diverse families. Segregation with the condition demonstrated for two of the variants (PMID 27208207) and functional studies provided for the remaining two variants (PMID 27696117).

Created: 5 Sep 2017, 8:46 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
3-methylglutaconic aciduria, type VIII 617248

Publications

• 27208207
• 27696117