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Improved understanding of the phenotypic spectrum associated with nonsyndromic orofacial clefting (OFC) has the potential to inform efforts to uncover the etiology of this complex trait. Prior studies report that individuals with OFC are characterized by impaired olfactory ability. In this study, we test whether olfactory dysfunction extends to the unaffected parents of children with OFC. The University of Pennsylvania Smell Identification Test was used to measure olfactory ability in a sample of 60 unaffected mothers and fathers with cleft-affected children. The proportion of deficit was compared with reference data obtained from published sex- and age-specific norms on more than 2700 individuals. The proportion of deficit was significantly higher in unaffected parents compared with baseline control subjects (41.7% vs 12.6%; P &lt; 0.001). Of unaffected fathers, 41.7% displayed evidence of deficit compared with 15.1% of male control subjects (P = 0.001), whereas 41.7% of mothers exhibited deficits compared with 10.4% of female control subjects (P &lt; 0.001). Olfactory deficits are present at a high proportion in the unaffected parents of individuals with OFC. This suggests that the deficits observed in affected cases may not simply be a secondary consequence of surgical repair and may instead be an informative phenotype reflecting underlying etiology.

Evidence of Olfactory Deficits as Part of the Phenotypic Spectrum of Nonsyndromic Orofacial Clefting