First case of medulloblastoma in O’Donnell-Luria–Rodan syndrome: a case series of three patients with KMT2E variants and literature review

Abstract Background O’Donnell–Luria–Rodan syndrome (ODLUROS) is an autosomal dominant neurodevelopmental disorder associated with KMT2E variants. Central nervous system malignancies have not been reported in this syndrome. This study aimed to analyze the clinical, endocrine, and genetic features of three pediatric patients with ODLUROS. Methods We retrospectively reviewed the clinical, neuroimaging, endocrine, and genetic data of three pediatric patients with ODLUROS. Whole-exome sequencing (WES) was performed on the probands and their parents, and variant pathogenicity was classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines. To evaluate the complete phenotypic spectrum—including potential oncological manifestations—we conducted a systematic literature search in PubMed, Wanfang Data, and the China National Knowledge Infrastructure (CNKI) for studies published between January 2019 and April 2025 using the search terms “KMT2E” and “O’Donnell–Luria–Rodan syndrome”. Results Affected children presented with core phenotypic features, including recurrent vomiting, developmental delay, intellectual disability, speech impairment, short stature, and posterior fossa abnormalities. WES identified heterozygous KMT2E variants (NM_182931.3), classified as pathogenic or likely pathogenic according to ACMG criteria. Notably, one patient developed large-cell/anaplastic medulloblastoma—a specific tumor type not previously reported in individual with ODLUROS. A comprehensive literature review of 75 published cases demonstrated substantial phenotypic overlap with the current cohort. Conclusions To our knowledge, this is the first report of large-cell/anaplastic medulloblastoma in a patient with ODLUROS, expanding the phenotypic clinical spectrum of this disorder and highlighting the value of genetic testing in establishing KMT2E-related diagnoses. However, the occurrence of medulloblastoma in this individual does not directly confirm a causative role for the KMT2E variant in tumorigenesis. While long-term oncological surveillance warrants consideration, further evidence is needed to clarify cancer risk in the ODLUROS population.