Beckwith-Wiedemann syndrome and differential diagnosis [37 genes]

Beckwith-Wiedemann syndrome (BWS) is a congenital overgrowth disorder with a variable clinical expression, characterized by macrosomy, macroglossia, hemihyperplasia, abdominal wall defects (exomphalos or umbilical hernia), organomegaly, neonatal hypoglycemia, and typical ear features. It is also associated with kidney alterations and increased risk of childhood tumors, particularly Wilms tumor and hepatoblastoma. Growth is usually normalized in late childhood, neurological development is generally normal, and the overall prognosis is good with appropriate clinical follow-up.

 1-5 / 10,000 (ORPHA:116)

Requesting an NGS panel for Beckwith-Wiedemann syndrome can confirm diagnosis in cases with an atypical phenotype, helps differentiating other overgrowth syndromes, and guides genetic and reproductive counseling. This test acts as a valuable complement to techniques targeting imprinting, methylation, and uniparental disomy of locus 11p15.5, providing a more comprehensive molecular overview of the case when both approaches are integrated.

The clinical indication to request an NGS panel targeting Beckwith-Wiedemann syndrome focuses on patients with signs of obergrowth or hemihyperplasis whose diagnosis is not clear after initial testing for methylation, uniparental disomy, and imprinting of locus 11p15.5. It is also particularly indicated upon suspicion of familial forms, presence of compatible history, or a phenotype that could match alternative overgrowth syndromes, where identifying variants in genes included in the panel may guide definitive diagnosis, tumor monitoring, and genetic counseling.