Novel mutations in IRF6 in nonsyndromic cleft lip with or without cleft palate: when should IRF6 mutational screening be done?

摘要

Cleft lip with or without cleft palate (CL/P) is one of the most common congenital malformations observed in humans, with an incidence of approximately 1/1,000 live births [Gorlin et al, 2001]. CL/P has been associated with more than 300 recognizable syndromes, but is more often observed as an isolated birth defect referred as nonsyndromic cleft lip with or without cleft palate (NSCL/P). The etiology of NSCL/P is multifactorial and recurrence risk varies from 4% to 10% according to the number of affected individuals in the family and the relationship to the propositus [Harper, 2004]. In contrast, Van der Woude syndrome (VWS) is the most common form of syndromic CL/P and accounts for 2% of all orofacial cleft cases [Schutte et al., 1996]. VWS is caused by mutations in the Interferon Regulatory Factor 6 gene (IRF6) [Kondo et al., 2002] and is inherited as an autosomal dominant disorder with an estimated penetrance of 89-99% [Burdick et al., 1985; Gorlin et al., 2001].