IQSEC2-related encephalopathy in males due to missense variants in the pleckstrin homology domain

Pathogenic variants in IQ motif and SEC7 domain containing protein 2 (IQSEC2) gene cause a variety of neurodevelopmental disorders, with intellectual disability as a uniform feature. We report five cases, each with a novel missense variant in the pleckstrin homology (PH) domain of the IQSEC2 protein. Male patients all present with moderate to profound intellectual disability, significant delays or absent language and speech and variable seizures. We describe the phenotypic spectrum associated with missense variants in PH domain of IQSEC2, further delineating the genotype-phenotype correlation for this X-linked gene.

Automated summary

Pathogenic variants in IQSEC2 gene play a key role in neurodevelopment, with intellectual disability as a common feature. We report five cases with novel missense variants in the PH domain, resulting in moderate to profound intellectual disability and language developmental delay.