Gi), Harelip and Associated Cleft Palate (G2), and Posterior Cleft Palate (G3

CONGENITAL MALFORMATIONS 47 9. HARELIP (GI), HARELIP AND ASSOCIATED CLEFT PALATE (G2), AND POSTERIOR CLEFT PALATE (G3) It has long been realized that many cases of Fusion of the face and the anterior palate is nor- harelip (GI) and harelip with cleft palate (G2) are mally complete by about the end of the seventh week similar in etiology. There have been numerous of embryonic life. However, midline fusion of the reports of monozygotic twins where both had GI or posterior palate does not start until the ninth week G2 and of others where one twin had GI and the and then proceeds from front to back. Closure is other G2. Fogh-Andersen (1942), in his now classical not complete until about the twelfth week. If the report, was the first to point to the differing familial anterior failure is very gross, it is understandable that and epidemiological pattern of these conditions and proper fusion, at least anteriorly, of the posterior that of posterior cleft palate (G3) with intact anterior palate is virtually impossible. palate and lip. There is an undue frequency of cases Such gross failure of anterior fusion may result of Gl and G2 in some families and of G3 in others. if it is impossible for the lateral maxillary processes However, cases of Gl or G2 and cases of cleft palate to meet the premaxilla which is developed from the only (G3) do not occur in the same families more fronto-nasal process. In some cases this situation frequently than would be expected by chance. These may be the result of complete failure of proper findings have been confirmed in many studies, which development or descent of the fronto-nasal process. may be exemplified by those of Fraser (1960), Fraser In its extreme form this maldevelopment leads to & Calnan (1961), Fujino et a]. (1963) and Woolf et disorganization of the face when the orbits are very al. (1963). It is on such evidence and additional close together or fused and there is anophthalmia or indications from the present data that cases of GI microphthalmia. Several of these cases are classified and G2 are considered separately from those of G3 in the N group, and others, probably of this group, in what follows. have been classified as M when from a description such as " absence of face " it did not seem justified HARELIP (G1) AND HARELIP AND ASSOCIATED to classify them in G2. CLEFT PALATE (G2) In other cases the fronto-nasal process descends As mentioned above there is evidence from family but it is abnormal and projects anteriorly on a and twin studies of the homogeneity of many cases different plane from the rest of the developing face, of Gl and G2. This homogeneity is also evident on so that again there is nothing with which the lateral anatomical grounds. All degrees occur, from a maxillary processes can fuse. In these cases the slight " nick " in the lip to cases where the harelip is philtrum is usually on the tip of the nose. complete and there are in addition notches of Both the above types of developmental failure varying depth in the alveolar margin. These defects appear almost invariably to determine also failure represent essentially the end-results of different of fusion of the whole of the posterior palate. degrees of unsuccessful penetration of the mesoderm Developmentally, they are quite different in origin by those outgrowths from the ectodermal grooves from simple cleft lip or such cleft with extension to which form the face. In these cases, the palatal the anterior palate only. lesion affects only the fusion of the palate or pre- It will be clear from the above that we should maxilla which carries the incisor teeth. In cases expect some homogeneity in the etiology of GI and where only harelip occurs in one member of the G2 cases, as the minor degrees of G2 with an intact family and harelip and cleft palate in another the posterior palate are essentially greater degrees of palatal cleft is almost invariably of this limited type GI. However, we should also expect some hetero- (Kernahan & Stark, 1958). However, there are also geneity between GI and G2 cases and within the cases of harelip and cleft palate where the palatal G2 category because they would be expected to lesion is much larger, extending far back into the include also cases where grossly aberrant develop- posterior palate in the midline, so that the cleft is ment of the fronto-nasal process was the primary complete or nearly complete. defect. 48 A. C. STEVENSON AND OTHERS HARELIP (G1) AND HARELIP AND CLEFT PALATE (G2) GI and G2: sex proportions (M/M+F) IN THE PRESENT DATA In both GI and G2 there was an excess of males; the sex proportions in the summed data from the Frequencies centres being 0.62 and 0.65 respectively. In the two From Table 9.1 it will be seen that in most centres combined the proportion was 0.64. There appears there were more cases of G2 than of GI and that, from Table 9.1 to be a fairly consistent distribution over-all, there were approximately twice as many of this male excess, even allowing for sampling cases of the former. There is a positive correlation fluctuations of rather small numbers. The similarity between the frequencies of the two groups in the in the sex proportions of Gl and G2 accord with a various centres (GI and G2: r = + 0.432, P < 0.05). hypothesis of considerable homogeneity of some cases at least in these groups. Geographic and ethnic variations GJ and G2: mortality The highest frequencies of G1 + G2 were in Johannesburg, Kuala Lumpur, Santiago, Hong Kong Of 407 infants with GI or G2, 47 were stillborn and Singapore. Direct comparisons have to be or died in hospital, a mortality of 115 per 1000 total viewed with caution but these conditions are seldom births. This is significantly higher than in all single missed at birth unless there is only a minimal not- births (16 617/416 615; P < 0.001). Some of the ching of the lip. All the reported series used for children who died may have had associated internal examination of these influences appear to have been malformations which determined death. Unfor- of cases presenting for surgical repair. On the basis tunately, only a few of these cases were examined of such data some authors have decided that birth at autopsy. It might be surmised that a proportion order is the important variable (Fujino et al., 1963) of children who died had a type of GI or G2 which and others that maternal age has the greater influence was the effect of homozygosity for a recessive gene. (Fraser & Calnan, 1961; Rank & Thomson, 1960). However, of the 47 who died three were the offspring In the present data standardization for maternal age of related parents. Seventeen of the surviving did not substantially influence relative frequencies children had consanguineous parents. (Consan- and those in the centres mentioned above were guinity associated with these and other malforma- still the highest. tions is considered in section 19.) Harelip (GJ) and harelip and cleft palate (G2) Frequencies in ethnic groups occurring as one of two or more malformations It has often been noted that frequencies were high in the same child (Group N) in Asiatic people and in particular Japanese and GI and G2 occur frequently as one of several Chinese (e.g., Neel & Schull, 1956). In Singapore malformations (i.e., N group). One of these defects the frequencies in Chinese, Malays and Indian was found in 56 of 329 (17.0%) of those classified ethnic groups were respectively 42/31 503 (1.33 per in the N group. Of these 56 infants, 30 (53.6 Y.) were 1000), 10/4850 (2.06 per 1000) and 4/3085 (1.30 per stillborn or died in hospital. This high mortality 1000). In the same order in Kuala Lumpur the is partly, but probably not entirely, explicable in ethnic group frequencies were 15/8625 (1.74 per terms of the severity of associated malformations. 1000), 5/2151 (2.32 per 1000) and 3/4094 (0.73 per The malformation groupings are shown in Table 9.2. 1000). These figures suggest that the frequencies in It seems likely, as already mentioned, that a few Malays were at least as high as in Chinese. It is other cases are also closely related in etiology- noteworthy, however, that in Manila in those namely, those said to have absence of the face, which classified as " Malay " the frequency of Gl + G2 probably means complete failure of development of was 1.11 per 1000, or little above the mean in all the fronto-nasal process, so determining malforma- centres of 0.98 per 1000. In both Singapore and tions not really differentiable from some of the cases Kuala Lumpur, however, the frequency in Indians called anophthalmia or microphthalmia with harelip was the lowest of the three-about the mean of that and cleft palate. in all centres and similar to the figures from Bombay A remarkable feature of multiple malformations and Calcutta. There were no cases in Cape Town, which include GI or G2 is the high proportion of where the " Cape Coloured " population has a males. In one of the 56 cases the sex was indetermin- substantial contribution from Malay blood. ate but of the remaining 55, 43 were males, a pro- CONGENITAL MALFORMATIONS 49 portion (M/M+F) of 0.78. This is even higher than tion is, however, significantly different from that in cases where Gl or G2 was the only malformation.

Load more