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DR. W. L. ADEYEMO, BDS, FMCDS, FWACS, PHD, FICS ASSOCIATE PROFESSOR/CONSULTANT ORAL AND MAXILLOFACIAL SURGEON UNIVERSITY OF LAGOS/LUTH
Pathogenesis
The embryologic basis of cleft palate is failure of the
mesenchymal masses derived either from thee maxillary prominences (i.e., the lateral palatine processes) or from the MNP (i.e., either the median palatine process or the nasal septum) to meet and fuse with each otherr.
Cleft lip results from failure of the maxillary
prominence on the affected side to unite with medial nasal prominence (unilateral)
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Common observations : Race incidence higher in orientals >whites >blacks 20% have a family history
Syndromic clefts in 1% to 8%
First degree relatives are 25 times more likely to have a
causes of cleft lip and palate in the literature. These reports have been derived from epidemiological studies, animal studies, and human genetic in vitro studies. Early studies suggested a multifactorial threshold model for the aetiology of nonsyndromic cleft lip and palate.
environmental and genetic factors has been suggested as follows: that genetic factors create susceptibility for cleft, clefts develops when environmental factors trigger the genetically susceptible phenotype.
Genetic influences
Reports have suggested that the proportion of
environmental and genetic factors varies with the sex of the affected individual, the severity of the cleft, the type of cleft (whether Syndromic or no-Syndromic, cleft lip with or without palate or isolated cleft palate, and unilateral and bilateral cleft. The duration and timing of the teratogens on the foetus also affects the severity of the anomaly
facial development that includes genes identified as growth factors, cytokines, self-signaling molecules, and structural proteins. Gene linkage and association studies have confirmed role for a number of these genes.
as molecular markers; that incorporate the severity of the phenotype and the addition of environmental variables facilitate the detection of even small gene effects and provide an increasing powerful platform for the collection of genetic data
Genetic influences
Studies in genetic influences have been
Small pedigree Low penetrance Genetic heterogenicity Varying influence of environmental factors All leading to different conclusions
BIXEL CLASSIFICATION
Syndromic variety; monogenic ,chromosomic or
isolated CP
CL/P loci OFC1 OFC2 OFC3 OFC4 OFC5/MSX1 OFC6/IRF6 OFC7/PVRL1 OFC8/TP73L
Chromosomic location 6p24-p23 2p13 19q13 4q21-q31 4q16 1q32.3-q41 1123.3 3q28
Year of identification 1990 1989 1995 1994 1997 1992 1998 1999
MTHFR
1q36
1995
TGFB3
14q24
1998
RAR
17q21.1
1992
Environmental influences
Drugs (modified by genetics, timing and dosage )
Phenytoin Thalidomide Vaproic acid Benzodiazepines Steroids Amphetamines Maternal Age Alcohol intake
Socioeconomic class
Vitamin B deficiencies
TGFA/Smoking TGFA/Alcohol TGFA/Vitamins MSX1/Smoking MSX1/Alcohol TGFB3/Smoking TGFB3/Alcohol RARA/Smoking MTHFR/Vitamins P450/Smoking GST/Smoking EPHX1/Smoking
specific homoebox (MSX1), in aetiology of cleft lip and palate defect (Butali et al. 2011). Other environmental factors have also been implicated.
have one or more associated anomalies Syndrome: A group of symptoms regularly occurring together and appear to have a related cause Over 250 known syndromes are associated with clefting
Syndromic clefts
Clefting is a secondary event(>157 syndromes) Trisomy 13 Turners Downs Cri Du Chat Treacher Collins Pierre Robins
Meckels
Wolf Hirsclorn Van der Woude
Implications
Gene therapy Vitamin B supplements for at risk groups Prenatal counselling
summary
origin often unmasked by environmental influences. Environmental interactions in the aetiology of cleft is well documented.