Orbicularis oris muscle defects as an expanded phenotypic feature in nonsyndromic cleft lip with or without cleft palate

Nonsyndromic cleft lip ± cleft palate is a complex disease with a wide phenotypic spectrum; occult defects of the superior orbicularis oris muscle may represent the mildest subclinical form of the lip portion of the phenotype. This study used high-resolution ultrasonography to compare the frequency of discontinuities in the OO muscle in 525 unaffected relatives of individuals with nonsyndromic cleft lip ± cleft palate versus 257 unaffected controls. OO muscle discontinuities were observed in 54 (10.3%) of the non-cleft relatives, compared to 15 (5.8%) of the controls - a statistically significant increase (P = 0.04). Male relatives had a significantly higher rate of discontinuities than male controls (12.0% vs. 3.2%; P = 0.01); female relatives also had a higher rate of discontinuities than female controls, but the increase was not statistically significant (8.9% vs. 7.4%; P = 0.56). These data confirm the hypothesis that subepithelial OO muscle defects are a mild manifestation of the cleft lip phenotype. Identification of subepithelial OO muscle defects may be important in a clinical setting, as a means of providing more accurate recurrence risk estimates to relatives in cleft families. Furthermore, the expansion of the cleft lip ± cleft palate phenotypic spectrum should improve the power of genetic studies.