A Rare Case of Osteosarcoma in an Individual with the Recurrent n.64_65insT Variant in the RNU4-2 Gene

Background: Variants in the RNU4-2 gene are one of the most common autosomal causes of Neurodevelopmental Disorders (NDD). Despite the increased recognition of their clinical impact, associated malignancies have not been previously reported. Case Findings: We present a male patient with the most common RNU4-2 gene variant, n.64_65insT. At age 21, he was diagnosed with Osteosarcoma (OS), a condition not previously reported in affected individuals, and died 5 months later. Clinical Implication: This unique case expands the phenotype of RNU4-2-related neurodevelopmental disorder and highlights the importance of screening for cancer-related symptoms in patients with RNU4-2 gene variants.