BHLHE22 monoallelic and biallelic variants cause a neurodevelopmental disorder with agenesis of the corpus callosum, intellectual disability, abnormal muscle tone and movement abnormalities

Corpus callosum dysgenesis (CCD) is among the most common developmental brain disorders. Diagnostic yield even after exome sequencing (ES) is currently below 50%, with many more single genes to be associated with CCD.

We report on 15 individuals with BHLHE22 variants linked to a previously unidentified autosomal dominant and recessive neurodevelopmental disorder with corpus callosum agenesis and spasticity.

A molecular diagnosis has the potential to improve early intervention and clinical management. ES may be used to clinically identify BHLHE22 variants associated with callosal agenesis, intellectual disability and spasticity.