Folate pathway and nonsyndromic cleft lip and palate.

BACKGROUND: Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common complex birth defect. Periconceptional supplementation with folic acid, a key component in DNA synthesis and cell division, has reduced the birth prevalence of neural tube defects and may similarly reduce the birth prevalence of other complex birth defects including NSCLP. Past studies investigating the role of two common methylenetetrahydrofolate reductase (MTHFR) single-nucleotide polymorphisms (SNPs), C677T (rs1801133) and A1298C (rs1801131), in NSCLP have produced conflicting results. Most studies of folate pathway genes have been limited in scope, as few genes/SNPs have been interrogated. Here, we asked whether variations in a more comprehensive group of folate pathway genes were associated with NSCLP, and were there detectable interactions between these genes and environmental exposures? METHODS: Fourteen folate metabolism-related genes were interrogated using 89 SNPs in multiplex and simplex non-Hispanic white and Hispanic NSCLP families. RESULTS: Evidence for a risk association between NSCLP and SNPs in NOS3 and TYMS was detected in the non-Hispanic white group, whereas associations with MTR, BHMT2, MTHFS, and SLC19A1 were detected in the Hispanic group. Evidence for over-transmission of haplotypes and gene interactions in the methionine arm was detected. CONCLUSIONS: These results suggest that perturbations of the genes in the folate pathway may contribute to NSCLP. There was evidence for an interaction between several SNPs and maternal smoking, and for one SNP with gender of the offspring. These results provide support for other studies that suggest that high maternal homocysteine levels may contribute to NSCLP and should be further investigated.

Evidence of gene-environment interaction for the IRF6 gene and maternal multivitamin supplementation in controlling the risk of cleft lip with/without cleft palate.

Although multiple genes have been identified as genetic risk factors for isolated, non-syndromic cleft lip with/without cleft palate (CL/P), a complex and heterogeneous birth defect, interferon regulatory factor 6 gene (IRF6) is one of the best documented genetic risk factors. In this study, we tested for association between markers in IRF6 and CL/P in 326 Chinese case-parent trios, considering gene-environment interaction for two common maternal exposures, and parent-of-origin effects. CL/P case-parent trios from three sites in mainland China and Taiwan were genotyped for 22 single nucleotide polymorphisms (SNPs) in IRF6. The transmission disequilibrium test was used to test for marginal effects of individual SNPs. We used PBAT to screen the SNPs and haplotypes for gene-environment (G×E) interaction and conditional logistic regression models to quantify effect sizes for SNP-environment interaction. After Bonferroni correction, 14 SNPs showed statistically significant association with CL/P. Evidence of G×E interaction was found for both maternal exposures, multivitamin supplementation and environmental tobacco smoke (ETS). Two SNPs showed evidence of interaction with multivitamin supplementation in conditional logistic regression models (rs2076153 nominal P=0.019, rs17015218 nominal P=0.012). In addition, rs1044516 yielded evidence for interaction with maternal ETS (nominal P=0.041). Haplotype analysis using PBAT also suggested interaction between SNPs in IRF6 and both multivitamin supplementation and ETS. However, no evidence for maternal genotypic effects or significant parent-of-origin effects was seen in these data. These results suggest IRF6 gene may influence risk of CL/P through interaction with multivitamin supplementation and ETS in the Chinese population.

Cultural and religious components in Nigerian parents' perceptions of the aetiology of cleft lip and palate: implications for treatment and rehabilitation.

The present study was conducted to find out the perceptions of mothers from two Nigerian ethnic groups who had children with cleft lip and palate (CLP) about the aetiology of the defect. Mothers of 16 children with CLP from the Yoruba ethnic group who attended the maxillofacial clinic of the Obafemi Awolowo University teaching hospital in southern Nigeria and 20 children with CLP from the Hausa/Fulani ethnic group who attended the maxillofacial clinic of the University of Maiduguri teaching hospital in northeastern Nigeria were interviewed over an 8-month period. We used standardised interviews including questions with ethnographic components to allow us to collect information about traditional beliefs about clefts. Interviews were recorded on tape for later analysis. Thirteen of the 16 parents from the Yoruba group attributed the aetiology of CLP to supernatural forces (evil spirits and ancestral spirits), while 16 of the 20 Hausa/Fulani parents attributed it to the "will of God". Twelve of 16 Yoruba parents had consulted traditional healers for treatment before coming to the hospital. Various plants and animal products were used to treat clefts and 10 of the Yoruba parents were referred to the hospital for further treatment by the traditional healers. Cultural and religious factors seem to have an important role in the explanations, labels and treatment that followed the birth of a child with CLP in this environment. There is a need for greater collaboration and sharing of information between modern medical practitioners and traditional healers.

The craniofacial team and the Navajo patient.

The craniofacial team at the University of New Mexico Medical Center in Albuquerque, New Mexico has treated a large population of Navajo Indians. Team awareness of the Navajo concept of health as man in balance with his environment has resulted in more expedient treatment of the Navajo children. An understanding of Navajo concerns with ghosts, skinwalkers, and rules for orderly living has allowed team members to integrate the family and the Navajo medicine man in caring for the children with craniofacial disease. Special concerns for informed surgical consent and genetic counseling of the Navajo are reviewed. Respect for the traditional Navajo healing ceremonies and special handling of disposed body parts in surgery are required of the health professionals caring for these people.