Retrospective identification of patients with SRRM2‐related neurodevelopmental disorder in a single tertiary children's hospital

Abstract SRRM2 ‐related neurodevelopmental disorder is a recently described genetic diagnosis caused by loss‐of‐function variants in SRRM2 . In order to understand the clinical spectrum of SRRM2 ‐related neurodevelopmental disorder, we performed a retrospective exome data and clinical chart review at a single tertiary children's hospital, Children's Hospital of Philadelphia (CHOP). Among approximately 3100 clinical exome sequencing cases performed at CHOP, we identified three patients with SRRM2 loss‐of‐function pathogenic variants, in addition to one patient previously described in the literature. Common clinical features include developmental delay, attention deficit hyperactivity disorder, macrocephaly, hypotonia, gastroesophageal reflux, overweight/obesity, and autism. While developmental disabilities are commonly seen in all individuals with SRRM2 variants, the degree of developmental delay and intellectual disability is variable. Our data suggest that SRRM2 ‐related neurodevelopmental disorder can be identified in 0.3% of individuals with developmental disabilities receiving exome sequencing.