Early onset or syndromic epilepsy

Gene: BORCS8

I don't know

Seizures were reported in 2/3 families who had been diagnosed with BORCS8-related early-infantile neurological disorder with severe intellectual disability, hypotonia and congenital heart disease in PMID:38128568.

Created: 30 Sep 2024, 1 p.m. | Last Modified: 30 Sep 2024, 1 p.m.

Panel Version: 6.7

Green List (high evidence)

Comment on list classification: There is sufficient evidence available (3 unrelated families) for the promotion of this gene to green rating in the next GMS update.

Created: 18 Sep 2024, 1:21 p.m. | Last Modified: 18 Sep 2024, 1:21 p.m.

Panel Version: 7.32

PMID:38128568 reported five patients from three unrelated families with homozygous or compound heterozygous loss of function missense and PTC variants in BORCS8 gene. All of them (5/5) presented with hypotonia, failure to thrive, global developmental delay, profound intellectual disability, muscle weakness and atrophy and dysmorphic features, while spasticity was present in 4/5 patients, and microcephaly, seizures and scoliosis were present in 3/5 patients. Optic atrophy was reported in all four patients assessed.

Zebrafish knockout of the orthologous brocs8 causes decreased brain and eye size, neuromuscular anomalies and impaired locomotion, recapitulating some of the key traits of the human phenotype. In addition, functional evidence from HEK293T cells were reported for both missense and PTC variants.

This gene has been associated with relevant phenotype in Gene2Phenotype ('moderate' rating on the DD panel), but not yet associated with any phenotypes in OMIM.
Sources: Literature

Created: 18 Sep 2024, 1:19 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
neurodevelopmental disorder, MONDO:0700092; intellectual disability, MONDO:0001071

Publications

• 38128568