Abstract
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.
Highlights
Cleft lip or palate (CL/P) is a common human congenital defect promptly recognized at birth
Differentiation, and apoptosis, which are essential for appropriate lip and palate morphogenesis, are regulated by complex molecular signaling pathways; 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
Within CL/P, cleft lip with or without cleft palate (CL ± P) is considered a distinct entity from cleft palate only (CP), based on the different embryonic origin when palate development occurs, that is, the closure of the palatal shelves occurs between 8th and 12th weeks of the human gestation [5] while lip formation is concluded at the 7th week [6]
Summary
Luciano Abreu Brito, Joanna Goes Castro Meira, Gerson Shigeru Kobayashi, and Maria Rita Passos-Bueno. Human Genome Research Center, Institute of Biosciences, University of Sao Paulo, 05508-090 Sao Paulo, SP, Brazil. 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, are difficult to predict, as in the case of the chromosomal region 8q24, the most corroborated locus predisposing to nonsyndromic CL/P. 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
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