Revisiting the Recurrence Risk of Nonsyndromic Cleft Lip with or without Cleft Palate

Sub-epithelial defects (i.e., discontinuities) of the superior orbicularis oris (OO) muscle appear to be a part of the phenotypic spectrum of cleft lip with or without cleft palate (CL +/- P). Analysis of the OO phenotype as a clinical tool is hypothesized to improve familial recurrence risk estimates of CL +/- P. Study subjects (n = 3,912) were drawn from 835 families. Occurrences of CL +/- P were compared in families with and without members with an OO defect. Empiric recurrence risks were calculated for CL +/- P and OO defects among first-degree relatives (FDRs). Risks were compared to published data and/ or to other outcomes of this study using chi-square or Fisher's exact tests. In our cohort, the occurrence of CL +/- P was significantly increased in families with OO defects versus those without (P< 0.01, OR = 1.74). The total FDR recurrence of isolated OO defects in this cohort is 16.4%; the sibling recurrence is 17.2%. The chance for one or more FDRs of a CL +/- P proband to have an OO defect is 11.4%; or 14.7% for a sibling. Conversely, the chance for anyFDR of an individual with anOOdefect to haveCL +/- P is 7.3%; or for a sibling, 3.3%; similar to published recurrence risk estimates of nonsyndromic (NS) CL +/- P. This study supports sub-epithelial OO muscle defects as being part of the CL +/- P spectrum and suggests a modification to recurrence risk estimates of CL +/- Pby utilizing OO defect information. (C) 2010 Wiley-Liss, Inc.