Expanding the phenotypic spectrum of Rauch-Steindl syndrome: A novel NSD2 variant with atrial septal defect in a Chinese patient

Background Rauch-Steindl syndrome (RSS) is a very rare autosomal dominant disorder caused by pathogenic variants in the NSD2 gene, characterized by dysmorphic facial features, prenatal and postnatal growth retardation, and variable developmental delay. Case presentation : We report the case of a 16-month-old Han Chinese girl who presented with typical features of RSS, including prenatal and postnatal growth failure, low body mass index, global developmental delay, expressive language impairment, infantile feeding difficulties, and distinctive dysmorphic facies (triangular face, broad forehead, high anterior hairline, deep-set eyes, full cheeks, thin and high nasal bridge, thick lower lip vermilion). She also exhibited mildly increased muscular tone in the lower limbs, transient recurrent respiratory infections, and a persistent atrial septal defect (ASD). Whole-exome sequencing identified a novel de novo heterozygous nonsense variant (NM_001042424.3: c.1466C > G, p.Ser489Ter) in exon 6 of the NSD2 gene on chromosome 4, which was classified as pathogenic according to ACMG guidelines. Notably, the patient exhibited an ASD that persisted through follow-up beyond 31 months of age—a feature not previously documented in RSS. Conclusions This case report expands both the phenotypic and genotypic spectrum of NSD2 -associated RSS.