The Pattogenesis of Submucous Cleft Palate

Abstract

Submucous cleft palate (SMCP), while not a serious problem in infancy, has an incidence of 1: 1 200 births. At this figure it is second only to bifid uvula in order of frequency of congenital anomalies of the palate. The pathogenesis of SMCP has not been determined in man, though two disparate mechanisms, anomalous shelf fusion or failure of mesodermal proliferation have been proposed. An animal model of SMCP is described in which the anomaly has characteristics in common with the condition in man. Serial study of the mouse fetus in which SMCP has been induced by maternal dosage with phenytoin throughout the teratogenosensitive period supports the hypothesis of interference with mesodermal differentiation. A centripetal gradient of differentiation in the palatal shelf is described, commencing at the nasal foramen and extending to the uvula. When this gradient is disturbed by teratogens, after fusion of the palate, either SMCP plus bifid uvula, or bifid uvula alone may result, the anomaly being determined by the stage of onset in relation to the antero-posterior gradient of risk. Study of the animal defect assists with identification of the causal mechanism in man. The findings support the proposal that the teratogenosensitive period of palatogenesis in man should be regarded as extending from early embryo-genesis to about the 12th week of development. Until that time agents can act to interfere with the developing palatal plates and the velar mesoderm in such a way that SMCP and bifid uvula, microforms of cleft palate, could result.