BACKGROUND Suggestive, but not conclusive, studies implicate many genetic variants in oral cleft etiology. We used a large, ethnically homogenous study population to test whether reported associations between nonsyndromic oral clefts and 12 genes (CLPTM1, CRISPLD2, FGFR2, GABRB3, GLI2, IRF6, PTCH1, RARA, RYK, SATB2, SUMO1, TGFA) could be confirmed. METHODS Thirty-one single nucleotide polymorphisms (SNPs) in exons, splice sites, and conserved non-coding regions were studied in 509 patients with cleft lip with or without cleft palate (CLP), 383 with cleft palate only (CP), 838 mothers and 719 fathers of patients with oral clefts, and 902 controls from Ireland. Case-control and family-based statistical tests were performed using isolated oral clefts for the main analyses. RESULTS In case-control comparisons, the minor allele of PTCH1 A562A (rs2066836) was associated with reduced odds of CLP (OR: 0.29, 95% CI: 0.13–0.64 for homozygotes) whereas the minor allele of PTCH1 L1315P (rs357564) was associated with increased odds of CLP (OR: 1.36, 95% CI: 1.07–1.74 for heterozygotes and OR: 1.56, 95% CI: 1.09–2.24 for homozygotes). The minor allele of one SUMO1 SNP, rs3769817 located in intron 2, was associated with increased odds of CP (OR: 1.45, 95% CI: 1.06–1.99 for heterozygotes). Transmission disequilibrium was observed for the minor allele of TGFA V159V (rs2166975) which was over-transmitted to CP cases (P=0.041). CONCLUSIONS For 10 of the 12 genes, this is the largest candidate gene study of nonsyndromic oral clefts to date. The findings provide further evidence that PTCH1, SUMO1, and TGFA contribute to nonsyndromic oral clefts.

BACKGROUND-Cleft lip with or without cleft palate (CLP) and cleft palate only (CPO) have an inherited component and, many studies suggest, a relationship with folate. Attempts to find folaterelated genes associated with clefts have, however, often been inconclusive. This study examined four SNPs related to folate metabolism (MTHFR 677 C→T, MTHFR 1298 A→C, MTHFD1 1958 G→A, and TC II 776 C→G) in a large Irish population to clarify their relationship with clefts.

Objective: This systematic review sought to evaluate the consensus in the literature regarding the surgical management of VPD and to determine whether a particular procedure results in superior speech outcome or less morbidity Design: A systematic review was carried out according to PRISMA-P guidelines. Systematic review software was used to facilitate 3-stage screening and data extraction by 2 reviewers.Setting: University teaching hospital.Patients, Participants: Studies that reported perceptual speech assessment or obstructive sleep apnea (OSA) in patients who had undergone surgery for VPD were included in the review. Interventions: Four categories of surgery for VPD were examined-pharyngeal flap, sphincter pharyngoplasty, palatoplasty, and posterior pharyngeal wall augmentation.Main outcome measures: Perceptual speech assessment, need for further surgery, and occurrence of OSA were the outcomes of interest.Results: Eighty-three relevant studies were identified, comprising data on 4011 patients. Pharyngeal flap was the most common procedure (64% of patients). Overall, 70.7% of patients attained normal resonance and 65.3% attained normal nasal emission. There was no notable difference in speech outcomes, need for further surgery, or occurrence of OSA across the 4 categories of surgery examined. Heterogeneous groups of patients were reported upon and a variety of perceptual speech assessment scales were used. Conclusions: There is a lack of consensus in the literature to guide procedure selection for patients with VPD. The development of a standardized minimum data set to record postoperative speech, OSA, and patient-reported outcomes is required.