Expanding the phenotypic spectrum of Rauch–Steindl syndrome: A case study of a novel NSD2 mutation in an Indian patient

Rauch–Steindl syndrome (RAUST) is a rare genetic disorder characterised by poor growth, distinctive facial dysmorphisms and variable developmental delays. It is a milder variant of Wolf–Hirschhorn syndrome and is associated with mutations in the NSD2 gene. This study presents a case of RAUST with a novel NSD2 mutation, expanding the phenotypic spectrum of the syndrome. An 18-month-old Indian boy was referred to Basaveshwar Teaching and General Hospital for failure to thrive. Born preterm at 1.7 kg with intrauterine growth restriction, he presented with severe growth retardation, microcephaly and facial dysmorphism including dolichocephaly, triangular facies and cleft palate. Developmental assessment revealed significant delays in motor and speech milestones. Genetic analysis identified a heterozygous NSD2 gene variant (chr 4: g.1978839del; p.Pro1343GlnfsTer49), leading to a frameshift and premature truncation of the protein. Whole exome sequencing was performed on peripheral blood DNA, revealing the pathogenic NSD2 mutation. The analysis also highlighted the variability in phenotypic expression of RAUST, including additional anomalies such as undescended testes. The proband’s clinical features align with RAUST, with the identified NSD2 mutation contributing to the observed dysmorphisms and developmental delays. Despite normal neuroimaging, the wide spectrum of symptoms, including additional anomalies, underscores the complex phenotypic variability of RAUST. The mother’s similar phenotypic features suggest possible autosomal dominant inheritance with variable expressivity. This case highlights the diverse presentation of RAUST and the critical role of NSD2 mutations in its pathogenesis. It emphasises the need for genetic analysis in diagnosing RAUST and understanding its broad phenotypic spectrum. Further studies are necessary to explore the full range of clinical manifestations and inheritance patterns associated with RAUST.