Orofacial clefts (OFCs) are facial malformations that happen during early pregnancy and have a complex and heterogeneous etiology, involving both genetic and environmental risk factors. This project examined the association between maternal nutrition, folaterelated biomarkers, candidate genes involved in one-carbon metabolism (OCM), and OFCs in order to achieve more comprehensive knowledge of how nutrition and genetics influence OFC risk. First, the association between maternal periconceptional multivitamin (PCMV) use, maternal dietary patterns during the periconceptional period, and OFC risk was examined. This study showed that neither PCMV use nor healthy dietary pattern score alone was individually associated with OFC risk. However, the combination of PCMV use and a higher score reflecting the ideal Dietary Approach to Stop Hypertension diet was associated with 55% reduction in the risk of isolated OFCs, evidence that the prevention of OFCs may require attention to both PCMV use and improving maternal diets. Second, the association between maternal multivitamin use, folic acid supplemental intake, and measured blood folate levels in case mothers of OFC children and control mothers was examined. Mothers who had an OFC-affected pregnancy compared with control mothers had lower mean levels of plasma folate in both multivitamin users and non-users. At levels of folic acid intake >400µg/day, the difference in plasma folate between case mothers and control mothers narrowed, evidence that higher folate intake levels may be required for mothers with a history of OFC-affected pregnancy. The ability to utilize supplement folic acid might be modified by MTHFR C677T genotype. In mothers with 677CC genotype, both case and control mothers’ plasma folate concentrations responded to increased levels of folic acid supplemental intake, although case mothers’ plasma folate concentrations were always significantly lower than control mothers’ until folate supplemental intake reached 400µg. In mothers with 677CT genotype, control but not case mothers’ plasma folate concentrations responded to increased levels of folic acid supplemental intake. In mothers with 677TT genotype, case but not control mothers’ plasma folate concentrations responded to increased levels of folic acid supplemental intake. Lastly, variations in folate-related OCM genes were examined in association with risk of OFCs using GWAS data and the case-parent trio approach. Several genes in the OCM pathway were associated with isolated, non-syndromic OFCs with some through genetic effects alone but most through gene-environment interaction effects with maternal multivitamin supplementation during periconceptional period and maternal biomarker concentrations for OCM-related nutrients. These results emphasize the need to consider gene-environment interactions when searching for genes influencing isolated OFCs. Reduction in the prevalence of OFCs could have tremendous importance. The results of this dissertation may help identify factors important to OFCs etiology and in turn, provide valuable targets for preventive intervention. Children born with an OFC require medical care from birth until adulthood and encounter a higher mortality rate. The costs incurred from caring for children born with OFCs not only include the clinical care of many disciplines but also involve the emotional disturbance and social and employment exclusion for affected individuals. Reducing the risk of OFCs would lessen considerable financial and emotional burdens to families and societies.

Magister Chirurgiae Dentium (MChD) / An analysis of the oral health related quality of life (OHRQoL) of patients with orofacial clefts at the Wentworth Foundation in Durban, KZN is presented. Objectives: To assess whether the OHRQoL of orofacial cleft patients varies amongst different age groups, genders or cleft types as well as demographic factors. Method: 46 participants, aged 8- 18, completed a self-administered Child Oral Health Impact Profile (COHIP) questionnaire. Results: The most prevalent cleft type was the Unilateral Cleft Left, 45.7%. The COHIP mean score was 84.195 (SD 18.244) ranging from 35 to 110. The age related subscales which were statistically significant included Functional well-being (p value: 0.0456), School Environment (p value: 0.0145) and Treatment Expectancy. The subscale School Environment was statistically significant for: Transport (p value: 0.0267) and Place of accommodation (p value 0.028). The Oral Health subscale and the Educational level were statistically significant (p value 0.043). Conclusion: Statistically significant age-related differences and demographic factors were noted. The OHRQoL of cleft patients was low largely due to socioeconomic factors and difficulty accessing multidisciplinary care. Therefore, our findings highlight the importance of establishing a Cleft lip and palate multidisciplinary facility for these patients in the Wentworth foundation and subsidised transport to the Wentworth Foundation is recommended.

Introduction : Les déterminants génétiques du statut en folate (MTHFR, MTR, NOS3, SHMT1 et 2, MTHFD1 et 2, MTHFS, SLC19A1, ABCB1, FOLR2 et FOLH1) sont variablement associés au risque primaire de fentes chez les sujets hispaniques, irlandais, norvégiens et polonais. Ce risque est associé aux déterminants génétiques de la vitamine B12 (TCN2) en Italie et au métabolisme de la choline (BHMT, BHMT2 et PCYT1A) en Pologne. Des polymorphismes génétiques du gène CBS, une enzyme majeure de la voie de la transulfuration, y sont associés en Italie. But de l'étude : Nous avons étudié les déterminants génétiques des fentes labio-maxillo-palatines en France en lien avec le métabolisme des monocarbones par SNP Array. Méthodes : Notre étude cas-témoins porte sur 250 enfants, leurs mères (200), et 521 contrôles appareillés. Une analyse multiplex de 384 SNPs (77 gènes sélectionnés dans la base NCBI et à partir d'études in silico), a été réalisée par technologie Golden Gate Illumina (BeadExpress Reader, San Diego, California). Toutes les analyses ont été réalisées en modèles additifs, dominants et récessifs. Résultats : En analyse univariée chez les mères en modèle additif, rs2124459 CBS, rs35789560 FPGS, rs234709 CBS, rs4816 PCMT1, rs737865 COMT, rs4820889 TCN2, rs13043752 AHCY, rs2168781 SHMT1 et rs1801229 CUBN sont associés au risque primaire de fentes. Après correction de Bonferroni, seul CBS rs2124459 1552+1199A-->G atteint la significativité dans le modèle additif avec P= 0,009 (OR (Dd) versus (dd) = 0,46 (0,26 to 0,81) et (DD) versus (Dd) = 0,51 (0,26 to 0,97)). En modèle dominant le P= 0,09 (OR (DD, Dd) versus (dd) = 0,40 (0,23 to 0,69). Chez les enfants, CBS rs2124459 est associé au risque de fentes dans les modèles additif et dominant, avec des P=0.026 et P=0.011respectivement. Discussion et conclusion: CBS est très fortement associée au risque primaire de fentes chez les mères et les enfants. Ces résultats montrent une mise en jeu prépondérante de la voie de la transulfuration dans l'étiologie des fentes en France / Background : Monocarbons determinants are involved in the etiology of cleft lip with or without cleft palate, based on ethnical background and periconceptional mother's diet. Genetic polymorphisms of actors of folate and monocarbon availability (MTHFR, MTR, NOS3, SHMT1 and 2, MTHFD1 and 2, MTHFS, SLC19A1, ABCB1, FOLR2 and FOLH1) are in association with the primary risk of oro-facial cleft in contrasting ways in Hispanic, non-Hispanic-white, Irish, Norwegian or Polish subjects. The actors of B12 availability like TCN2 are only involved in Italian subjects. Cholin metabolism (BHMT, BHMT2 and PCYT1A) is reported in Polan. CBS, actor of transulfuration pathway?s, is in association with cleft risk in Italian studies. Aim : This study is built to determine the primary risk of cleft (OCF) in association with single nucleotid polymorphisms of the actors of folate, B12 and choline availability, monocarbons metabolism and transulfuration pathway?s in France. Methods : We performed a case-control study of 250 children and their mothers (200), and 521 matches controls. A multiplex analysis of 384 SNPs (77 genes), selected by NCBI databases research's and in silico studies was performed, using GoldenGate Illumina technology (BeadExpress Reader, San Diego, California) with appropriate genotyping controls. Genotypes with call rate under 0.95 and SNPs with Hardy-Weinberg disequilibrium linkage were excluded. SNP association analyses were performed applying additive, dominant and recessive models to the data. Results :In univariate analysis of mothers versus controls for additive model 9 SNPs were found in association with primary risk of cleft, concerning rs2124459 CBS ; rs35789560 FPGS ; rs234709 CBS ; rs4816 PCMT1 ; rs737865 COMT ; rs4820889 TCN2 ;rs13043752 AHCY ; rs2168781 SHMT1 ; rs1801229 CUBN. After multiple testing correction, only CBS rs2124459 1552+1199A-->G reached statistical significance in additive models, with P= 0.009 in the additive model (OR (Dd) versus (dd) = 0.46 (0.26 to 0.81) and (DD) versus (Dd) = 0.51(0.26 to 0.97)). P= 0.09 in the dominant model (OR (DD, Dd) versus (dd) = 0.40 (0.23 to 0.69), respectively. In patients, CBS rs2124459 was significantly associated with a reduced risk of OFC in both additive and dominant models, with respectively P=0.026 and P=0.011. Discussion and conclusion : This study reported an intronic SNP from CBS not previously described, with a strong association with primary risk of cleft in mothers and child. These results argues to the predominant way of transulfuration in etiology of oro-facial cleft in France

Orofacial clefts are frequent congenital anomalies. A combination of genetic and environmental factors contributes to their formation. Orofacial clefts together with growth retardation belong among the indicators of embryo toxicity. This thesis is focused on the potential relationship between birth weight and orofacial clefts of newborns born in Czech Republic. The non-syndromic cleft lip, cleft lip and palate, isolated cleft palate and patients with Pierre-Robin sequence are discussed here. Evaluation of the relationship between the birth weight and orofacial clefts was performed on the base of statistical analysis. The differences were tested in children with different types of orofacial clefts and in cleft patients compared to healthy control. Statistical analysis of variance demonstrated that the type and severity of the cleft (unilateral/ bilateral) does not affect birth weight of newborns with orofacial clefts. Newborns with non-syndromic clefts had reduced birth weight in comparison to healthy controls. Cleft patients with Pierre-Robin sequence (syndromic form of cleft) did not differ in birth weight from healthy children. To verify the results obtained in patients with orofacial clefts that the birth weight is lower in these patients compared to control, two experiments on a chicken model...

The thesis deals with the impact of orofacial cleft (cleft lip and palate) on family psychosomatics within the psycho-social-ethical framework. It summarises the history, classification and treatment of cleft disorders, followed by an analysis of real-life problems occuring in the process of taking care of a baby with orofacial cleft, specifies terms frequently used when discussing orofacial cleft as a stigma: stigma and stigmatisation, norm and normality, beauty and ugliness.The phenomena of fear and pain, difficulty in communication with the child{\crq}s and the parents{\crq} immediate social surroundings and, the barriers between experts and the parents are dealt with in the thesis. The thesis focuses on orofacial cleft anomalies in connection with Christian ethics. It analyses the relation of abortion and orofacial disorders and the role of hope in the process of taking care and upbringing of a child suffering from this disorder.

The topic of this diploma thesis is an analysis of interdisciplinary approach to children with orofacial clefts. The first chapter deals with theoretical base and defines terminology - communication, communication disabilites. It also defines anatomy and physiology of nasal cavity and oral cavity. The second chapter relates to issues of orofacial clefts. It describes classification, etiology, symptomatology, prevention, aestetic and psychosocial impacts and orofacial cleft children care. The third chapter deals with occurence of communication disabilites of children with orofacial clefts. It focuses on the definition of palatholaly, velopharyngeal inadequacy and it describes various linguistic levels and speech therapy and intervention. The fourth chapter is empiric and it deals with analysis of interdisciplinary approach to children with orofacial clefts. In research processes there were used scientific literature analysis, anamnestic data analysis and available specialized materials analysis. Based on all of these materials six case studies were created. Main goal of this empiric chapter was to analyze interdisciplinary approach to children with orofacial clefts. Partial goals were to analyze whether information provided by experts and doctors to parents of newborn children with orofacial cleft...

The present study explored the effect of the birth of a child with a cleft lip and palate on family functioning within the context of family systems theory. Five families, each with a child who was born with a cleft lip and palate, were included in the study. The five couples were all married and they were the biological parents of their children whose ages ranged from two months to five years. All five sets of parents were initially interviewed together and then had separate individual interviews where the Family Assessment Measure-III was administered. The results reflected each family's distinctive patterns of interaction and how they adapted to the birth of a child with an orofacial cleft. Factors found to affect family functioning included: External support systems, individual coping skills, family rules and boundaries, open communication and cohesion among family members. / Psychology / M. A. (Psychology)

The present study explored the effect of the birth of a child with a cleft lip and palate on family functioning within the context of family systems theory. Five families, each with a child who was born with a cleft lip and palate, were included in the study. The five couples were all married and they were the biological parents of their children whose ages ranged from two months to five years. All five sets of parents were initially interviewed together and then had separate individual interviews where the Family Assessment Measure-III was administered. The results reflected each family's distinctive patterns of interaction and how they adapted to the birth of a child with an orofacial cleft. Factors found to affect family functioning included: External support systems, individual coping skills, family rules and boundaries, open communication and cohesion among family members. / Psychology / M. A. (Psychology)