Cleft Lip and Palate: Seasonal Incidence, Birth Weight, Birth Rank, Sex, Site, Associated Malformations and Parental Age: A Statistical Survey

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Abstract
An attempt has been made to provide pointers to the elucidation of the aetiology of this complex of congenital malformations. The excess of males in Groups I and III suggests that females are less susceptible to the interactions of polyfactorial genetical and environmental factors which are concerned in the pathogenesis of this sub-division. There is evidence that advanced maternal age at first birth may predispose to a Group I malformation in females and to a more severe Group III malformation in males. In the same way other less potent factors may cause a cleft lip in males, with a lower threshold of resistance, but nothing at all in females. The increased paternal age, in Group III especially, suggests (Penrose, 1955) that fresh paternal mutations are concerned in the pathogenesis of this condition. Such mutations might be especially important in the fathers of female patients, who are older, since it has been argued above that females may have a higher threshold of resistance to environmental and genetical factors responsible for these malformations. There is suggestive evidence, both because of the very different sex ratio in Group II and because of the incidence of isolated cleft palate as a constituent of various complex syndromes thought to be inherited in a dominant manner, that single genes may play a large part against a background of polyfactorial genes and environmental factors in the determination of this condition. The moderately raised parental age, once again more marked for fathers than mothers, suggests that fresh mutations may play a role. Such fresh mutations both in this Group and in Group III compensate for genes lost due to early death, as in Pierre Robin''s syndrome.