Rare epigenetic changes of the Beckwith-Wiedemann Spectrum: Case report

Abstract

BACKGROUND:  The Beckwith-Wiedemann Syndrome is a rare genetic condition characterized by  resulting congenital hyper growth caused by an alteration in 11p15.5. Its classic clinical manifestation consists in macroglossia, macrosomia, abdominal wall defects and higher predisposition for embryonic tumors. Due to its high phenotypic variability, it has been renamed to Beckwith-Wiedemann Spectrum. The diagnosis is made by clinical analysis and confirmation through molecular exams that analyze genetic and epigenetic alterations in 11p15.5. Nevertheless,  there is little disclosure in the literature, hence necessary new relevant case reports. OBJECTIVE: The objective of this work was to report two rare cases of IC1 hypermethylation in the Beckwith-Wiedemann Spectrum, correlating the clinical aspects of the disease with results from Multiplex Ligation-Dependent Probe Amplification molecular analysis, and thus contributing to the scientific literature. METHODS: The medical records and molecular analysis reports of 2 pediatric patients were analyzed and compared with the scientific literature of similar cases. RESULTS: Hypermethylation of the H19-DMR region, also known as IC1, a rare cause of Beckwith-Wiedemann Spectrum, was revealed in both patients. Macrosomia, presented by patient 1, was the most consistent and prevalent clinical finding in cases of IC1 hypermethylation, however, post-natal overgrowth was more prevalent in cases of IC2 hypomethylation, differing from the clinical finding presented by patient 2. CONCLUSION: The case report makes a significant contribution to the scientific literature by identifying rare and under-reported occurrences, and based on the convergences and divergences found between the literature and the clinical and molecular findings of the reported patients, and due to the phenotypic variety of the Beckwith-Wiedemann Spectrum and the lack of updated scientific literature, the importance of disseminating Beckwith-Wiedemann Spectrum cases is emphasized.