Rubinstein-Taybi syndrome with ganglioneuroblastoma: a case report and literature review.

Background: Rubinstein-Taybi syndrome (RSTS) is a rare genetic disorder characterized by severe global developmental delay (GDD) and distinctive facial grimacing. The loss of function of the CREBBP and EP300 genes is recognized as a genetic etiology of RSTS. However, the association between CREBBP variants and an increased risk of tumors remains unknown, despite multiple reports of tumor comorbidities related to RSTS. The aim of this study is to elucidate the tumors associated with CREBBP variants in the context of RSTS by presenting a case of ganglioneuroblastoma (GNB) in a patient diagnosed with RSTS.

Methods: We describe a 9-month-old male patient exhibiting distinctive facial features, enorchia, and GDD. Whole exome sequencing (WES) revealed a de novo pathogenic variant in NM_004380 (CREBBP): c.1068del (p.Gln356Hisfs*33). At one year of age, the patient experienced an unexplained fever lasting for two months, and the definitive diagnosis of GNB was established.

Conclusions: We report a case of RSTS co-morbid with GNB and conduct phenotypic and genotypic analyses of 43 individuals with documented CREBBP variants and associated tumors in the literature. We observed that frameshift variations are common in malignancies among the individuals studied, while more microdeletions were noted in patients with benign tumors. Currently, there is insufficient evidence to support a correlation between the types of CREBBP variants and specific tumor types. Further research is required to clarify the role of CREBBP variants in tumorigenesis.