Mutations in the interferon regulatory factor 6 (IRF6) gene are known to cause van der Woude syndrome (VWS), a common syndromic form of oro-facial clefting characterized by the familial occurrence of mixed clefting (cleft lip with or without a cleft palate and cleft palate alone in the same family) and lower lip pits. As lip pits are not present in all cases of VWS, IRF6 mutations can cause a phenotype identical to non-syndromic clefting. However, recent studies failed to identify IRF6 mutations in sporadic and familial non-syndromic clefting, concluding that testing for IRF6 was not warranted for sporadic or familial non-syndromic clefting. Here we report on two families that demonstrate familial mixed clefting in which mutations in IRF6 were identified, suggesting that IRF6 testing does have a role in familial, non-syndromic OFC.

The project proved overall valuable in improving medical student understanding of genetic counseling and may be applied to a variety of medical education settings to improve patient care.

Orofacial clefting is a common condition found in 1 per 700 to 1 per 1000 births. Although most cases are isolated, a subset is caused by a specific genetic mutation. Specific gene tests have been used for recognizable syndromes such as velocardiofacial syndrome or van der Woude syndrome, where the cleft is associated with other anomalies. However, many cleft lip and palate patients have other anomalies but do not fit in to a recognizable syndrome. For these patients, chromosome analysis has been a first-line genetic test; however, in the past few years, a new form of genetic testing has become available for these patients: array comparative genome hybridization (aCGH). We present a 7-month-old male infant with cleft palate, developmental delay, and a family history of velopharyngeal insufficiency in whom aCGH array was used to identify a small deletion on the short (p) arm of chromosome 7. This defect, which was also found in the mother, was undetected by chromosome analysis. In summary, this case demonstrates that aCGH is a new diagnostic tool that is useful in the evaluation of select cases of orofacial clefting. Array comparative genome hybridization should be considered when the suspicion for a genetic etiology of the clefting remains strong despite a normal cytogenetic analysis.