Molecular characteristics

Variants in the IRF2BPL gene have been shown to cause NEDAMSS. Mutations in IRF2BPL are scattered throughout the gene and are predicted to be protein truncating for individuals with the most severe phenotype. Missense variants in IRF2BPL have also been observed in individuals with a milder phenotype including seizures and autism without the neurodevelopmental regression. To date, all of the individuals have been found to have de novo, autosomal dominant variants in IRF2BPL. All variants identified so far have been detected through NGS-level genomic sequencing (either whole exome sequencing or whole genome sequencing).