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. 2023 Aug;191(8):2149-2155.
doi: 10.1002/ajmg.a.63302. Epub 2023 May 22.

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

Kelly E Regan-Fendt  1 , Alyssa L Rippert  1 , Livija Medne  1   2 , Cara M Skraban  1   2   3 , Jeshua DeJesse  1 , Christopher Gray  1   2 , Sara L Reichert  4 , Nicholas P Staropoli  4 , Francis Jeshira Reynoso Santos  1   3 , Ian D Krantz  1   2   3 , Jill R Murrell  4   5 , Kosuke Izumi  1   2   3
Affiliations

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

Kelly E Regan-Fendt et al. Am J Med Genet A. 2023 Aug.

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.

Keywords: exom sqequencing; neurocognitive impairment; nuclear speckle; reanalysis.

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