Professionals

Based on a first cohort of 11 individual, pathogenic BHLHE22 variants are associated with a severe neurodevelopmental disorder with corpus callosum agenesis, developmental delay, cognitive impairment, tone and movement abnormalities, and oculomotor/vision deficits.
Inheritance pattern is both autosomal dominant and autosomal recessive. Four de novo missense variants were in the highly conserved helix-loop-helix domains of the BHLHE22 protein and one recurrent homozygous frameshift variant, p.(Gly74AlafsTer18), was in seven affected individuals from five unrelated families. Individuals with biallelic homozygous variants were more severely affected.