Human genetic factors in nonsyndromic cleft lip and palate: an update.
ABSTRACT Nonsyndromic cleft lip and/or palate (or orofacial cleft, OFC) is a malformation characterized by an incomplete separation between nasal and oral cavities without any associated anomalies. The last point defines the distinction between syndromic and nonsyndromic OFC. Nonsyndromic OFC is one of the most common malformations among live births and is composed of two separate entities: cleft lip with or without cleft palate (CL+/-P) and cleft palate isolated (CPI). Because of the complex etiology of nonsyndromic OFC, which is due to the differences between CL+/-P and CPI, and the heterogeneity of each group, caused by the number of genes involved, the type of inheritance, and the interaction with environmental factors, we reviewed those genes and available loci in the literature whose involvement in the onset of nonsyndromic OFC has more sound scientific evidence. Genetic studies on human populations have demonstrated that CL+/-P and CPI have distinct genetic backgrounds and, therefore, environmental factors probably disclose only these malformations. In CL+/-P several loci, OFC from 1 to 10 have been identified. The first locus, OFC1, has been mapped to chromosome 6p24. Other CL+/-P loci have been mapped to 2p13 (OFC2), 19q13.2 (OFC3) and 4q (OFC4). OFC5-8 are identified by mutations in the MSX1, IRF6, PVRL1, and TP73L gene, respectively. OFC9 maps to 13q33.1-q34, whereas OFC10 is associated with haploinsufficiency of the SUMO1 gene. In addition, MTHFR, TGF-beta3, and RARalpha play a role in cleft onset. In CPI one gene has been identified (TBX22) at present, but others are probably involved. Greater efforts are necessary in order to have a complete picture of the main factors involved in lip and palate formation. These elements will permit us to better understand and better treat patients affected by OFC.
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ABSTRACT: Clefts of the lip (CL), the palate (CP), or both (CLP) are the most common orofacial congenital malformations found among live births, accounting for 65% of all head and neck anomalies. The frequency and pattern of orofacial clefts in different parts of the world and among different human groups varies widely. Generally, populations of Asian or Native American origin have the highest prevalence, while Caucasian populations show intermediate prevalence and African populations the lowest. To date, little is known regarding the epidemiology and pattern of orofacial clefts in Tanzania. A retrospective descriptive study was conducted at Bugando Medical Centre to identify all children with orofacial clefts that attended or were treated during a period of five years. Cleft lip and/or palate records were obtained from patient files in the Hospital's Departments of Surgery, Paediatrics and medical records. Age at presentation, sex, region of origin, type and laterality of the cleft were recorded. In addition, presence of associated congenital anomalies or syndromes was recorded. A total of 240 orofacial cleft cases were seen during this period. Isolated cleft lip was the most common cleft type followed closely by cleft lip and palate (CLP). This is a departure from the pattern of clefting reported for Caucasian and Asian populations, where CLP or isolated cleft palate is the most common type. The distribution of clefts by side showed a statistically significant preponderance of the left side (43.7%) (χ2 = 92.4, p < 0.001), followed by the right (28.8%) and bilateral sides (18.3%). Patients with isolated cleft palate presented at very early age (mean age 1.00 years, SE 0.56). Associated congenital anomalies were observed in 2.8% of all patients with orofacial clefts, and included neural tube defects, Talipes and persistent ductus arteriosus. Unilateral orofacial clefts were significantly more common than bilateral clefts; with the left side being the most common affected side. Most of the other findings did not show marked differences with orofacial cleft distributions in other African populations.BMC Oral Health 01/2011; 11:5.