RESUMEN
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.
Asunto(s)
Labio Leporino/complicaciones , Fisura del Paladar/complicaciones , Ácido Fólico/metabolismo , Genes/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple/genética , 5-Metiltetrahidrofolato-Homocisteína S-Metiltransferasa/genética , Betaína-Homocisteína S-Metiltransferasa/genética , Ligasas de Carbono-Nitrógeno/genética , Labio Leporino/etnología , Labio Leporino/genética , Fisura del Paladar/etnología , Fisura del Paladar/genética , Hispánicos o Latinos/genética , Humanos , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Óxido Nítrico Sintasa de Tipo III/genética , Proteína Portadora de Folato Reducido/genética , Timidilato Sintasa/genética , Población Blanca/genéticaRESUMEN
Pediatric vascular anomalies can be difficult to diagnose and complex to treat. One must be able to distinguish hemangiomas from various vascular malformations, as well as appreciate their dynamic course with time. Thorough understandings of the clinical and diagnostic techniques used to evaluate these lesions are paramount for the treating surgeon. In addition, knowledge of current treatments from watchful waiting to radical extirpation is mandatory. This must all be done in the setting of a developing child. We present a current review of the literature regarding the comprehensive care of pediatric vascular lesions.