Title : Human genetic factors innon-syndromic cleft lip and palate
Abstract:
Cleft lip (CL), cleft lip with or without cleft palate (CL/P) and isolated cleft palate (CP), collectively termed oral clefts (OC), are the second most common birth defects among newborn. [1-5] These defects arise in about 1 in 700 live-born babies, with ethnic and geographic variation. Approximately 75% of CL/P and 50% of CP cases are isolated defects and no other deformities are found in those children. Those OCs are therefore called non-syndromic[1-5].Although OC is usually not a life-threatening condition, many functions such as feeding, digestion, speech, middle-ear ventilation, and hearing, respiration, facial and dental development can be disturbed because of the structures involved. [1-6] These problems can also cause emotional, psychosocial and educational difficulties. Affected children need multidisciplinary care from birth until adulthood.2 Orofacial clefts pose a burden to the individual, the family, and society, with substantial expenditure, and rehabilitation is possible with good quality care. Care for children born with these defects generally includes many disciplines – nursing, facial plastic surgery, maxillofacial surgery, otolaryngology, speech therapy, audiology, counselling, psychology, genetics, orthodontics, and dentistry. Fortunately, early and good quality rehabilitation of children with OC usually gives satisfactory outcomes. Identification of etiological factors for OC is the first step towards primary prevention. [1-9] Genetic factors contributing to CL/P formation have been identified for some syndromic cases, but knowledge about genetic factors that contribute to non-syndromic CL/P is still unclear. The high rates of familial occurrences, risk of recurrence, and elevated concordance rates in monozygotic twins provide evidence for a strong genetic component in non-syndromic CL/P. However,concordance in monozygotic twins ranges between 40% and 60%, which means that the exact inheritance pattern of OC is more complex. It has been suggested that the development of non-syndromic OC occurs as a result of the interaction between different genetic and environmental factors. [1-11] The identification of the genes responsible for diseases has been a major focus of human genetics over the past 40 years.The introduction of modern molecular methods, experimental animal knockout models and advances in the technique of gene mapping have provided new candidate genes for orofacial clefting, both for syndromic and non-syndromic cases. However, the results of earlier candidate-gene-based association studies, performed in different populations, have been conflicting, with only a few candidate loci being implicated in OC phenotypes. [1-12] This inconsistency indicates the challenges in searching associations with a relatively rare phenotype such as non-syndromic clefting. To date, genetic approaches to non-syndromic CLP have included: linkage analysis; association studies; identification of chromosomal anomalies or microdeletions in cases; and direct sequencing of DNA samples from affected individuals.[1-15]
Key Words: Orofacial clefts, genetics, candidate genes
