Progress toward discerning the genetics of cleft lip

Abstract

Purpose of review-Orofacial clefts are common birth defects with a known genetic component to their etiology. Most orofacial clefts are nonsyndromic, isolated defects, which can be separated into two different phenotypes: (1) cleft lip with or without cleft palate and (2) cleft palate only. Both are genetically complex traits, which has limited the ability to identify disease loci or genes. The purpose of this review is to summarize recent progress of human genetic studies in identifying causal genes for isolated or nonsyndromic cleft lip with or without cleft palate.Recent findings-The results of multiple genome scans and a subsequent meta-analysis have significantly advanced our knowledge by revealing novel loci. Furthermore, candidate gene approaches have identified important roles for IRF6 and MSX1. To date, causal mutations with a known functional effect have not yet been described.Summary-With the implementation of genome-wide association studies and inexpensive sequencing, future studies will identify disease genes and characterize both gene-environment and gene-gene interactions to provide knowledge for risk counseling and the development of preventive therapies.

Racial Variations in Velopharyngeal and Craniometric Morphology in Children: An Imaging Study

“…Chung and Kau (1985) hypothesized that clefting may be related to these morphological cranial variations, which in turn could be related to inherent craniofacial variations on the basis of race. Current research aims to identify the relationship of genetics to cleft markers (Lidral & Moreno, 2005;Vieira et al, 2015). However, to our knowledge, no studies have investigated gene association related to clefting across different racial groups.…”

Review on genetic variants and maternal smoking in the etiology of oral clefts and other birth defects

“…These facial defects require surgical, nutritional, dental, speech, medical, and behavioral interventions and impose a substantial economic and societal burden. Clefts are common birth defects (birth prevalence ranges from 1/500 to 1/2500, depending on geographic origins) whose etiology includes multiple genetic and environmental factors (Reviewed by Jugessur and Murray, 2005;Lidral and Moreno, 2005). The complex etiology of clefts affords opportunities to identify gene-gene or gene-environment interactions that can shed light on human embryology and its disturbances.…”

CRISPLD2: a novel NSCLP candidate gene

“…Numerous studies suggest that NSCLP results from the complex interaction of both genes and environmental factors. Folic acid deficiency, maternal smoking and anticonvulsant medications are some of the environmental influences that have been associated with NSCLP (3)(4)(5). Evidence for involvement of genes in NSCLP comes from family studies which show that: (1) the heritability of NSCLP in a Caucasian population is approximately 76%, (2) the rate of concordance is higher in monozygotic (25-40%) than dizygotic (3-6%) twins and (3) there is an increased relative risk to siblings (λ s = 30-40) compared to the general population (1,6).…”