Human orofacial clefts (OFCs) are congenital anomalies that result from the breakdown of normal mechanisms that regulate the formation of the human face. They could be syndromic or non-syndromic, with a global inciden...Human orofacial clefts (OFCs) are congenital anomalies that result from the breakdown of normal mechanisms that regulate the formation of the human face. They could be syndromic or non-syndromic, with a global incidence of 1:700 per live births. Environmental and genetic factors are thought to play various roles in the aetiology of OFCs. This study seeks to establish the diversity, distribution and pattern of inheritance of OFCs as well as environmental and other risk factors associated with OFCs in a Ghanaian population. A family-based, descriptive cross-sectional study that employed an interview-based survey questionnaire was used to obtain information from 467 families with history of OFCs. We employed chi-square statistics to analyse the data and used graphs to interpret the data. All previously reported subphenotypes of OFCs were observed by the present study. Clinically, about 12% of clefts in the study population were syndromic. The most common syndromic forms observed were Pierre Robin Sequence, cleft-with-club foot abnormalities and Van der Woude Syndrome. Only about 5% of clefts in the study cohort were familial. The study also established that lower level of education of parents, poverty, late antenatal care and dietary folate deficiency are major environmental factors associated with clefts in the Ghanaian population. In conclusion, OFCs are non-randomly distributed in Ghana and folate deficiency could likely be a source of genetic mutations and “epimutations” that cause OFCs, since folate is essential for DNA methylation, replication and repair as well as histone modification.展开更多
Cleft lip with or without cleft palate(CP) is one of the most common congenital malformations. Ultrasonographers involved in the routine 20-wk ultrasound screening could encounter these malformations. The face and pal...Cleft lip with or without cleft palate(CP) is one of the most common congenital malformations. Ultrasonographers involved in the routine 20-wk ultrasound screening could encounter these malformations. The face and palate develop in a very characteristic way. For ultrasonographers involved in screening these patients it is crucial to have a thorough understanding of the embryology of the face. This could help them to make a more accurate diagnosis and save time during the ultrasound. Subsequently, the current postnatal classification will be discussed to facilitate the communication with the CP teams.展开更多
Background: Cleft lip and/or palate are the most common orofacial malformations. Many studies, especially in developed countries have been conducted on this malformation, but in Burkina Faso, data are scarce and they ...Background: Cleft lip and/or palate are the most common orofacial malformations. Many studies, especially in developed countries have been conducted on this malformation, but in Burkina Faso, data are scarce and they are not specific to children. The aim of this study was to report the epidemiological, clinical and therapeutic aspects of cleft lip and/or palate in children in a low-income country. Materials and Method: The authors conducted a retrospective descriptive study based on data of three humanitarian missions of pediatric reconstructive facial surgery which took place in 2007, 2010 and 2014 at Clinique El Fateh-Suka in Ouagadougou, Burkina Faso. All children of 0 - 14 years of age, presenting with cleft lip and/or palate, were included in the study. Results: A total of 185 cases of cleft lip and/or palate were seen during these three humanitarian surgery missions. There were 100 boys and 85 girls. The average age of the children was 2.4 ± 3.2 years [0 - 12 years];there were 8.7% newborns. The commonest type of cleft was cleft lip and palate (49.7%) followed by isolated cleft lip (48.7%) and isolated cleft palate (1.6%). The left side was the most affected (49.2%). In 21.1% of cases, clefts were associated with other congenital malformations. In total, 150 of 185 (81.1%) children underwent surgery and there were no postoperative complications reported. Conclusions: Epidemiological and clinical characteristics of cleft lip and/or palate observed in this study are not very different from those described elsewhere in Africa. However, in our conditions, there are circumstances and structural factors which hinder the diagnosis and constitute challenges that must be addressed for adequate management of this congenital, highly disfiguring malformation.展开更多
The isolated type of orofacial cleft, termed non-syndromic cleft lip with or without cleft palate(NSCL/P), is the second most common birth defect in China, with Asians having the highest incidence in the world. NSCL/P...The isolated type of orofacial cleft, termed non-syndromic cleft lip with or without cleft palate(NSCL/P), is the second most common birth defect in China, with Asians having the highest incidence in the world. NSCL/P involves multiple genes and complex interactions between genetic and environmental factors, imposing difficulty for the genetic assessment of the unborn fetus carrying multiple NSCL/P-susceptible variants. Although genome-wide association studies(GWAS)have uncovered dozens of single nucleotide polymorphism(SNP) loci in different ethnic populations, the genetic diagnostic effectiveness of these SNPs requires further experimental validation in Chinese populations before a diagnostic panel or a predictive model covering multiple SNPs can be built. In this study, we collected blood samples from control and NSCL/P infants inHan and Uyghur Chinese populations to validate the diagnostic effectiveness of 43 candidate SNPs previously detected using GWAS. We then built predictive models with the validated SNPs using different machine learning algorithms and evaluated their prediction performance. Our results showed that logistic regression had the best performance for risk assessment according to the area under curve. Notably, defective variants in MTHFR and RBP4, two genes involved in folic acid and vitamin A biosynthesis, were found to have high contributions to NSCL/P incidence based on feature importance evaluation with logistic regression. This is consistent with the notion that folic acid and vitamin A are both essential nutritional supplements for pregnant women to reduce the risk of conceiving an NSCL/P baby. Moreover, we observed a lower predictive power in Uyghur than in Han cases, likely due to differences in genetic background between these two ethnic populations.Thus, our study highlights the urgency to generate the HapMap for Uyghur population and perform resequencing-based screening of Uyghur-specific NSCL/P markers.展开更多
文摘Human orofacial clefts (OFCs) are congenital anomalies that result from the breakdown of normal mechanisms that regulate the formation of the human face. They could be syndromic or non-syndromic, with a global incidence of 1:700 per live births. Environmental and genetic factors are thought to play various roles in the aetiology of OFCs. This study seeks to establish the diversity, distribution and pattern of inheritance of OFCs as well as environmental and other risk factors associated with OFCs in a Ghanaian population. A family-based, descriptive cross-sectional study that employed an interview-based survey questionnaire was used to obtain information from 467 families with history of OFCs. We employed chi-square statistics to analyse the data and used graphs to interpret the data. All previously reported subphenotypes of OFCs were observed by the present study. Clinically, about 12% of clefts in the study population were syndromic. The most common syndromic forms observed were Pierre Robin Sequence, cleft-with-club foot abnormalities and Van der Woude Syndrome. Only about 5% of clefts in the study cohort were familial. The study also established that lower level of education of parents, poverty, late antenatal care and dietary folate deficiency are major environmental factors associated with clefts in the Ghanaian population. In conclusion, OFCs are non-randomly distributed in Ghana and folate deficiency could likely be a source of genetic mutations and “epimutations” that cause OFCs, since folate is essential for DNA methylation, replication and repair as well as histone modification.
文摘Cleft lip with or without cleft palate(CP) is one of the most common congenital malformations. Ultrasonographers involved in the routine 20-wk ultrasound screening could encounter these malformations. The face and palate develop in a very characteristic way. For ultrasonographers involved in screening these patients it is crucial to have a thorough understanding of the embryology of the face. This could help them to make a more accurate diagnosis and save time during the ultrasound. Subsequently, the current postnatal classification will be discussed to facilitate the communication with the CP teams.
文摘Background: Cleft lip and/or palate are the most common orofacial malformations. Many studies, especially in developed countries have been conducted on this malformation, but in Burkina Faso, data are scarce and they are not specific to children. The aim of this study was to report the epidemiological, clinical and therapeutic aspects of cleft lip and/or palate in children in a low-income country. Materials and Method: The authors conducted a retrospective descriptive study based on data of three humanitarian missions of pediatric reconstructive facial surgery which took place in 2007, 2010 and 2014 at Clinique El Fateh-Suka in Ouagadougou, Burkina Faso. All children of 0 - 14 years of age, presenting with cleft lip and/or palate, were included in the study. Results: A total of 185 cases of cleft lip and/or palate were seen during these three humanitarian surgery missions. There were 100 boys and 85 girls. The average age of the children was 2.4 ± 3.2 years [0 - 12 years];there were 8.7% newborns. The commonest type of cleft was cleft lip and palate (49.7%) followed by isolated cleft lip (48.7%) and isolated cleft palate (1.6%). The left side was the most affected (49.2%). In 21.1% of cases, clefts were associated with other congenital malformations. In total, 150 of 185 (81.1%) children underwent surgery and there were no postoperative complications reported. Conclusions: Epidemiological and clinical characteristics of cleft lip and/or palate observed in this study are not very different from those described elsewhere in Africa. However, in our conditions, there are circumstances and structural factors which hinder the diagnosis and constitute challenges that must be addressed for adequate management of this congenital, highly disfiguring malformation.
基金supported by the open project of Beijing Advanced Innovation Center for Food Nutrition and Human Health,Chinathe National Natural Science Foundation of China(Grant No.81860370)+2 种基金Beijing Municipal Natural Science Foundation(Grant No.7182184)interdisciplinary medicine Seed Fund of Peking University(Grant No.BMU2017MB006),Chinasupported by the National Postdoctoral Program for Innovative Talents(Grant No.BX201600150),China
文摘The isolated type of orofacial cleft, termed non-syndromic cleft lip with or without cleft palate(NSCL/P), is the second most common birth defect in China, with Asians having the highest incidence in the world. NSCL/P involves multiple genes and complex interactions between genetic and environmental factors, imposing difficulty for the genetic assessment of the unborn fetus carrying multiple NSCL/P-susceptible variants. Although genome-wide association studies(GWAS)have uncovered dozens of single nucleotide polymorphism(SNP) loci in different ethnic populations, the genetic diagnostic effectiveness of these SNPs requires further experimental validation in Chinese populations before a diagnostic panel or a predictive model covering multiple SNPs can be built. In this study, we collected blood samples from control and NSCL/P infants inHan and Uyghur Chinese populations to validate the diagnostic effectiveness of 43 candidate SNPs previously detected using GWAS. We then built predictive models with the validated SNPs using different machine learning algorithms and evaluated their prediction performance. Our results showed that logistic regression had the best performance for risk assessment according to the area under curve. Notably, defective variants in MTHFR and RBP4, two genes involved in folic acid and vitamin A biosynthesis, were found to have high contributions to NSCL/P incidence based on feature importance evaluation with logistic regression. This is consistent with the notion that folic acid and vitamin A are both essential nutritional supplements for pregnant women to reduce the risk of conceiving an NSCL/P baby. Moreover, we observed a lower predictive power in Uyghur than in Han cases, likely due to differences in genetic background between these two ethnic populations.Thus, our study highlights the urgency to generate the HapMap for Uyghur population and perform resequencing-based screening of Uyghur-specific NSCL/P markers.
