DNMT3A R882C variant in a patient with a presumed pineal gland tumor, highlighting potential tumor susceptibility in Tatton-Brown-Rahman syndrome.

Tatton-Brown-Rahman syndrome (TBRS) is a rare overgrowth disorder caused by germline alterations in DNMT3A, a gene essential for DNA methylation and epigenetic regulation. Affected individuals typically present with tall stature, intellectual disability, and neurodevelopmental disorders, and they also demonstrate an increased susceptibility to neoplastic disease. Reported tumors include hematologic malignancies, with acute myeloid leukemia being the most notable, as well as solid tumors such as neuroblastoma, medulloblastoma, benign glioma, and pituitary adenoma. Despite this expanding tumor spectrum, pineal gland tumors have not previously been described in association with TBRS. Here, we present the first known case of a presumed pineal gland tumor in a patient with TBRS. Although the lesion lacks histopathologic confirmation and a sporadic occurrence cannot be excluded, this observation raises the possibility that germline DNMT3A alterations may predispose to a broader range of tumors than previously recognized. This report underscores the need for continued documentation of unusual tumor presentations in TBRS to further elucidate the biology of DNMT3A-related tumorigenesis.