Enhancing Genetic Insight: Chromosomal Microarray Enhances Understanding of Genetics in Rubinstein-Taybi Syndrome.

Abstract

Introduction: Rubinstein-Taybi syndrome (RSTS) is characterized by distinctive craniofacial features, growth deficiencies, and broad thumbs and halluces. Most diagnoses are made through sequence analysis of the CREBBP or EP300 genes. Here we focused on two cases diagnosed through chromosomal microarray analysis (CMA), highlighting the significance of genetic variations in RSTS.

Case presentation: After detailed clinical examinations and genetic evaluations of 2 patients with suspected RSTS, CMA was conducted to identify copy number variations. CMA revealed a 128-kb deletion in the CREBBP gene in case 1 presenting with dysmorphic features and growth delays. Case 2, a 14-month-old girl with global developmental delay and similar dysmorphic features, was found to have a 1,467-kb deletion encompassing part of the EP300 gene.

Conclusion: Our study underscores the importance of CMA as a critical diagnostic tool for RSTS, particularly in cases where sequence analysis fails to identify pathogenic variants. The identification of significant deletions in the CREBBP and EP300 genes through CMA not only confirms the diagnosis of RSTS but also expands our understanding of the genetic complexity of the syndrome. Since CMA is already included as part of the diagnostic evaluation for RSTS, these findings further emphasize its value in ensuring accurate diagnosis and improving the management of this rare condition.