A de novo NSD2 deletion in Rauch–Steindl syndrome with expanded orofacial manifestations: a case report

Rauch–Steindl syndrome is a rare autosomal dominant genetic disorder caused by pathogenic variants in the NSD2 gene, characterized by growth retardation, intellectual disability, and characteristic facial features. Although systemic manifestations have been increasingly recognized, the orofacial phenotype of this syndrome remains insufficiently defined. This report aims to provide a detailed description of the orofacial findings in a patient with Rauch–Steindl syndrome. Here, we report a 17-year-old male with growth retardation, mild intellectual disability, and characteristic facial features. Oral examination revealed a white nodular lesion at the midline of the dorsal tongue, multiple permanent tooth agenesis, and abnormal tooth morphology. Whole-exome sequencing combined with copy number variation analysis identified an approximately 10.13 kb deletion in the 4p16.3 region, encompassing exons 12–14 of the NSD2 gene. According to the American College of Medical Genetics and Genomics guidelines, this deletion was classified as pathogenic, thereby supporting the diagnosis of Rauch–Steindl syndrome. Based on the clinical and mycological findings, the lingual lesion was diagnosed as nodular median rhomboid glossitis with chronic Candida infection. The lesion partially regressed after topical antifungal therapy but persisted at the one-year follow-up. This case expands the phenotypic spectrum of Rauch–Steindl syndrome by delineating its orofacial manifestations, particularly dental agenesis and abnormal tooth development. The occurrence of nodular median rhomboid glossitis may represent a secondary consequence of altered immune homeostasis in a patient with an NSD2 variant, rather than a direct phenotypic manifestation of Rauch–Steindl syndrome. Our findings further support the multisystem involvement associated with NSD2 haploinsufficiency and highlight the importance of comprehensive dental evaluation in patients with this syndrome. Further studies with larger cohorts are warranted to systematically characterize the oral phenotype associated with Rauch–Steindl syndrome.