%0 Journal Article
%T Genetics and Management of the Patient with Orofacial Cleft
%A Luciano Abreu Brito
%A Joanna Goes Castro Meira
%A Gerson Shigeru Kobayashi
%A Maria Rita Passos-Bueno
%J Plastic Surgery International
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/782821
%X Cleft lip or palate (CL/P) is a common facial defect present in 1£¿:£¿700 live births and results in substantial burden to patients. There are more than 500 CL/P syndromes described, the causes of which may be single-gene mutations, chromosomopathies, and exposure to teratogens. Part of the most prevalent syndromic CL/P has known etiology. Nonsyndromic CL/P, on the other hand, is a complex disorder, whose etiology is still poorly understood. Recent genome-wide association studies have contributed to the elucidation of the genetic causes, by raising reproducible susceptibility genetic variants; their etiopathogenic roles, however, are difficult to predict, as in the case of the chromosomal region 8q24, the most corroborated locus predisposing to nonsyndromic CL/P. Knowing the genetic causes of CL/P will directly impact the genetic counseling, by estimating precise recurrence risks, and the patient management, since the patient, followup may be partially influenced by their genetic background. This paper focuses on the genetic causes of important syndromic CL/P forms (van der Woude syndrome, 22q11 deletion syndrome, and Robin sequence-associated syndromes) and depicts the recent findings in nonsyndromic CL/P research, addressing issues in the conduct of the geneticist. 1. Introduction Cleft lip or palate (CL/P) is a common human congenital defect promptly recognized at birth. Despite the variability driven by socioeconomic status and ethnic background,the worldwide prevalence of CL/P is often cited as 1£¿:£¿700 live births; nevertheless, the different methods of ascertainment may lead to fluctuations in the prevalence rates [1]. Essentially, CL/P results from failure of fusion of the maxillary processes or palatal shelves, which occur between the 4th and 12th weeks of embryogenesis (as reviewed by Mossey et al. [2]). Cellular processes of proliferation, differentiation, and apoptosis, which are essential for appropriate lip and palate morphogenesis, are regulated by complex molecular signaling pathways; therefore, genetic and environmental factors that dysregulate those pathways are subject of intensive research as it is expected that their understanding will accelerate the development of preventive measures. Maternal alcohol intake or exposure to tobacco and several chemicals, such as retinoic acid and folate antagonists (e.g., valproic acid), among others, has been shown to be teratogenic, thus representing risk factors to embryos during the first trimester of pregnancy (reviewed by Bender [3] and by Dixon et al. [4]). Despite their etiological importance
%U http://www.hindawi.com/journals/psi/2012/782821/