Hydrocephalus and moderate mental retardation in a boy with Van der Woude phenotype and IRF6 gene mutation

Area of Science:

• Genetics
• Medical Genetics
• Developmental Biology

Background:

• Van der Woude syndrome (VWS) is an autosomal dominant disorder characterized by cleft lip/palate and lower lip pits.
• Genetic heterogeneity and variable expressivity are common in VWS.
• The IRF6 gene is a known major contributor to VWS.

Observation:

• A proband presented with severe craniofacial dysmorphism, cleft lip and palate, CNS malformation, and intellectual disability.
• Affected family members exhibited lower lip pits and cleft lip, with varying severity.
• Pedigree analysis suggested an autosomal dominant inheritance pattern.

Findings:

• Genetic analysis revealed a pathogenic mutation (c.960G>C) in the IRF6 gene in the proband and his mother.
• A single nucleotide polymorphism (c.175-5C>G) in the IRF6 gene was identified in the proband and his father.
• These genetic findings correlate with the observed clinical phenotypes within the family.

Implications:

• This case expands the understanding of IRF6 mutations in VWS and their phenotypic spectrum.
• Early genetic testing can aid in diagnosing VWS and genetic counseling for affected families.
• Further research into genotype-phenotype correlations is warranted for better patient management.