ID #982 A rare case of medulloblastoma in a patient with Rubinstein-Taybi syndrome

Abstract Background Medulloblastoma (MB) is extremely rare in patients with Rubinstein–Taybi syndrome (RSTS). Literature reports 6 MB cases, making it the second most frequent CNS neoplasm after meningioma. MB arising in RSTS usually belongs to the non-WNT/non-SHH subgroup. We describe an additional case of MB in a patient with RSTS. Methods The patient, a 6-year-old girl, presented with classic MB at age 5. She was admitted to our clinic 3 weeks post-diagnosis. Gross total resection was followed by radiation therapy. Methylation profiling for molecular subgrouping was performed using NanoString technology. Characteristic RSTS features—broad angulated thumbs, ocular coloboma, global developmental delay, and dysmorphic traits—raised clinical suspicion, confirmed by whole-genome sequencing (WGS). Results NanoString analysis identified MB group 4. WGS revealed a novel heterozygous pathogenic germline CREBBP variant (NM₀04380. 3): c. 2239₂255del, p. (M747Dfs*79), diagnostic of RSTS. Radiotherapy included craniospinal irradiation 35. 2 Gy + 19. 8 Gy posterior fossa boost, omitting vincristine due to gastrointestinal toxicity. She is currently receiving the sixth cycles of maintenance chemotherapy (cisplatin, lomustine, vincristine) according to the HIT protocol, with grade 3–4 hematological toxicity as the only significant adverse event. Conclusions This is the first reported RSTS case with molecularly confirmed group 4 MB. CREBBP, a transcriptional co-activator, regulates DNA repair, cellular growth, differentiation, apoptosis, and tumor suppression. Although CREBBP’s causative role in MB predisposition is unproven here, the RSTS-MB association likely exceeds coincidence.