Families

Pathogenic BHLHE22 variants are associated with a neurodevelopmental disorder with abnormal brain anatomy. Out of 9 individuals, 8 showed major delays in overall development and had intellectual disabilities. All had abnormal muscle tone. Six showed abnormal movements, especially with their hands. Strabismus was common. Four had varying seizure histories or a positive electroencephalogram finding.

Individuals with one faulty copy of the gene BHLHE22, were able to either walk or crawl. Their language skills were limited, but not completely missing. Three out of four showed signs of autism and had low muscle tone. One individual was less severely affected, but showed spasticity.

In contrast, five individuals with two faulty copies of the gene BHLHE22 (called homozygous variants) were unable to walk or speak. Most had low truncal tone with arms and legs spasticity. Three had trouble swallowing, two needed feeding tubes, and two had scoliosis.