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Etiological subgroups in non‐syndromic isolated cleft palate. A genetic‐epidemiological study of 52 Danish birth cohorts

Isolated cleft palate (CP) is considered to be a heterogeneous trait with an important genetic contribution to the etiology. Multifactorial‐threshold models of non‐syndromic CP inheritance assume a female predominance. The present study of 52 Danish birth cohorts, using several ascertainment sources, identified 2301 CP cases. It was found that, although females tended to be more severely affected than males, the overall sex ratio was close to one. For the latter half of the study period (1962‐87), which probably had the best ascertainment, the sex ratio for non‐syndromic CP was 0.95 (95% C.I. 0.85‐1.07). Marked difference in sex ratios for non‐syndromic overt CP including the hard palate (CPH) and non‐syndromic overt CP of the soft palate only (CPS) (0.69 vs 1.00, p<1.00, p<0.05) suggested that these two conditions may be etiologically distinct, a hypothesis which is embryologically plausible. In agreement with this hypothesis, Danish family data from surgically treated CP cases showed a strong tendency to segregate only one of the CP subtypes within families. Future studies are recommended to test the existence of a possible etiological difference between CPH and CPS.