First medulloblastoma case reported in O’Donnell–Luria–Rodan syndrome

Researchers in China have reported what they describe as the first documented case of medulloblastoma in a child with O’Donnell–Luria–Rodan syndrome (ODLUROS), an autosomal dominant neurodevelopmental disorder associated with variants in the KMT2E gene. The findings, published as an open-access case report in BMC Pediatrics, come from a retrospective review of three pediatric patients with genetically confirmed ODLUROS, combined with a systematic search of the published literature on the syndrome. Until now, central nervous system malignancies had not been reported in this disorder.

All three children in the cohort showed the core clinical features previously associated with ODLUROS: recurrent vomiting, developmental delay, intellectual disability, speech impairment, short stature, and abnormalities of the posterior fossa, the region of the brain that houses the cerebellum and brainstem. Whole-exome sequencing performed on each affected child and their parents identified heterozygous variants in KMT2E (reference sequence NM_182931.3), which the team classified as pathogenic or likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines. The authors argue that genetic testing plays a decisive role in establishing KMT2E-related diagnoses.

To place their three patients in context, the researchers searched PubMed, Wanfang Data, and the China National Knowledge Infrastructure for studies published between January 2019 and April 2025 using the terms “KMT2E” and “O’Donnell–Luria–Rodan syndrome”. The review identified 75 previously published cases, which the authors found overlapped substantially in phenotype with their own cohort. Against this background, the standout observation was that one of the three patients developed large-cell/anaplastic medulloblastoma, a specific tumor type that had not previously been reported in any individual with ODLUROS.

The authors are careful about what this single observation can and cannot show. In their conclusions, they state that, to their knowledge, this is the first report of large-cell/anaplastic medulloblastoma in a patient with ODLUROS, and that the finding expands the recognized clinical spectrum of the disorder. However, they explicitly note that the occurrence of medulloblastoma in this one individual does not directly confirm a causative role for the KMT2E variant in tumor formation. A single case, in other words, establishes an association in one patient, not a cancer risk for the syndrome as a whole.

Even so, the report has practical implications for clinicians caring for children with KMT2E variants. The authors suggest that long-term oncological surveillance warrants consideration in this population, while emphasizing that further evidence is needed to clarify whether cancer risk is genuinely elevated in ODLUROS. The case report is framed as expanding the phenotypic spectrum of the syndrome and highlighting the diagnostic value of sequencing, rather than as establishing a new cancer syndrome.

For families and clinicians, the case underscores two points that the evidence supports. First, ODLUROS has a recognizable phenotypic profile—recurrent vomiting, developmental delay, intellectual disability, speech impairment, short stature, and posterior fossa abnormalities—that genetic testing can confirm through pathogenic or likely pathogenic KMT2E variants. Second, the phenotypic spectrum of the syndrome may not be fully mapped: with only 75 published cases available for comparison before this report, rare manifestations can still surface. As more individuals with KMT2E variants are identified and followed over time, the question of whether medulloblastoma represents a true complication of ODLUROS or a coincidental finding in one patient should become answerable with data rather than inference.

Subject of Research: First report of medulloblastoma in a patient with O'Donnell–Luria–Rodan syndrome

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

Article References: Jun, T., Yirou, W., Xiuqi, M., Shiyang, G., Wei, L., Yang, S., shuo, W., Ying, X., & Xiuming, W. (2026). First case of medulloblastoma in O’Donnell-Luria–Rodan syndrome: a case series of three patients with KMT2E variants and literature review. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07892-2

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07892-2

Keywords: First, case, medulloblastoma, Donnell-Luria, Rodan, syndrome, series, three, patients, KMT2E, variants, literature