Cleft palate: A genetic and epidemiologic investigation

Abstract

An examination of kindred histories of 561 Danish probands who have non‐syndromic CP has indicated that neither a multifactorial‐threshold model nor a single major locus model is completely compatible with the data. This suggests etiologic heterogeneity for CP, which was tested with kindred data. As recommended by Smith (1976), an attempt to define partially this heterogeneity within the CP phenotype was undertaken by grouping and comparing the kindred data. It is both reasonable and heuristic to propose that CP, as defined in this investigation, is composed of three groups: (1) Syndromic CP; (2) Familial CP, which appears to have an autosomal dominant component to its etiology, and (3) Non‐familial CP which, by demonstrating an increasing frequency of CP and a maternal age effect, appears to be related to environmental factors which may cause CP or other malformations.

Human genetic factors in nonsyndromic cleft lip and palate: An update

“…Shields et al [117] proposed the existence of two classes of nonsyndromic cleft palate: (1) familial CPI, which appears to have an autosomal dominant component to its etiology and (2) nonfamilial CPI, which, appears to be related to environmental factors. Carter et al [118] reported the findings in a large series of patients and suggested that the etiology is probably heterogeneous with some families showing modified dominant inheritance.…”

Parental age as a risk factor for non-syndromic oral clefts: A meta-analysis

“…8,9,14,15,19,20,[22][23][24][25]29,31,36,37,42,43,47,53,59,60,70,72,[75][76][77][78][79] Whilst three studies described potential bias or efforts to identify bias in Section 2, 41,76,80 12 studies reported having used statistical methods to control for confounders. 10,24,[30][31][32]42,[46][47][48]78,79,81 In Section 4, 23 studies properly reported the studies limitations 4,9,10,21,24,32,34,35,38,41,42,44,…”

“…9,10,39-49 The outcomes were not clearly defined in 29 studies. 14, [16][17][18]21,22,26,27,39,[49][50][51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67] Thirty-three studies did not define the exposure variables 7,8,14,15,18,22,23,34,40,41,[50][51][52][53][54][56][57][58][59][60][61][62][63][64][65][66]…”

Analysis of familial incidence of non-syndromic cleft lip and palate in a Brazilian population

“…In onther study comprised of 153 individuals with NSCL/P in Thailand, registered a positive familial history in 17.7% of cases (14). In the USA and Western Europe a genetic factor is suspected in about 40% of cases (17). Family clustering in CL/P has been characterized extensively, and epidemiological studies have proposed monogenic models with reduced penetrance, multifactorial models and mixed major gene/multifactorial models to explain its inheritance (18).…”