Williams-Beuren syndrome in monozygotic twins with variable expression

Area of Science:

• Genetics
• Pediatrics
• Medical Genetics

Background:

• Williams-Beuren syndrome (WBS) is a rare genetic disorder.
• Monozygotic (MZ) twins provide a unique model for studying genetic versus environmental influences on disease expression.
• Previous reports include five sets of MZ twins with WBS.

Observation:

• A new pair of MZ twins concordant for WBS is presented.
• Despite being genetically identical, the twins exhibited variable clinical manifestations of WBS.
• Monogenicity was confirmed through DNA fingerprinting, HLA, and blood group analysis.
• Both twins presented with characteristic WBS facial features, strabismus, developmental delay, mild supravalvular aortic stenosis (SVAS), pulmonary artery hypoplasia, and inguinal hernias.
• One twin had unilateral renal agenesis.
• A familial history of cleft lip/palate suggested a potential second, autosomal dominant disorder.

Findings:

• The study confirms WBS in MZ twins with differing clinical expressivity.
• Genetic linkage analysis in families with non-syndromic oral-facial clefts suggests a locus on chromosome 6.
• This observation provides a potential starting point for investigating WBS-associated loci.

Implications:

• The findings reinforce the hypothesis that WBS is a genetic disorder.
• Variable gene expression in MZ twins highlights the complexity of WBS.
• Further research into genetic loci may aid in understanding WBS pathogenesis and associated conditions.