scholarly journals Distinct blood DNA methylation profiles in subtypes of orofacial cleft

2017 ◽  
Author(s):  
Gemma C Sharp ◽  
Karen Ho ◽  
Amy Davies ◽  
Evie Stergiakouli ◽  
Kerry Humphries ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Cleft Lip ◽  
Molecular Mechanisms ◽  
Cleft Lip And Palate ◽  
Association Studies ◽  
Orofacial Cleft ◽  
Orofacial Clefts ◽  
Blood Samples ◽  
Aberrant Dna Methylation ◽  
Genomic Regions

AbstractBackgroundThere is evidence that different subtypes of orofacial cleft have distinct aetiologies, although the precise molecular mechanisms underlying these are unknown. Given the key role of epigenetic processes such as DNA methylation in embryonic development, it is likely that aberrant DNA methylation may also play a part in the development of orofacial clefts.MethodsIn this study, we explored whether blood samples from children with different cleft subtypes showed distinct DNA methylation profiles.In whole blood samples from 150 children from the Cleft Collective cohort study, we measured DNA methylation at over 450,000 sites on the genome. We then carried out epigenome-wide association studies (EWAS) to test the association between methylation at each site and cleft subtype (cleft lip only CLO n=50; cleft palate only CPO n=50; cleft lip and palate CLP n=50).ResultsWe found four genomic regions differentially methylated in CLO compared to CLP, 17 in CPO compared to CLP and 294 in CPO compared to CLO. These regions included several mapping to genes that have previously been implicated in the development of orofacial clefts (for example, TBX1, COL11A2, HOXA2, PDGFRA) and over 250 novel associations.ConclusionOur finding of distinct methylation profiles in different cleft subtypes might reflect differences in their aetiologies, with DNA methylation either playing a causal role in development of OFC subtypes or reflecting causal genetic or environmental factors.

Do Orofacial Clefts Impair Breastfeeding and Increase the Prevalence of Anemia?

2021 ◽  
pp. 105566562110543
Author(s):  
Aluísio Eustáquio de Freitas Miranda-Filho ◽  
Heloisa de Sousa Gomes ◽  
Roberta Bessa Veloso Silva ◽  
Nelson Pereira Marques ◽  
Hercílio Martelli ◽  
...  
Keyword(s):  
Statistical Analysis ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
The Other ◽  
Deficiency Anemia ◽  
Control Group ◽  
Orofacial Cleft ◽  
Orofacial Clefts ◽  
History Of ◽  
Prevalence Of Anemia

Objective This study aimed to correlate the prevalence of iron deficiency anemia and breastfeeding with orofacial clefts in children. Design Data on the participant profile, presence and type of the cleft lip and/or palate (CL/P), and records on anemia and breastfeeding were collected from patients’ charts, and submitted to statistical analysis by χ2 test ( p < .05; software SPSS 23.0). Results Two-hundred and ten files were divided according to: CL/P presence (cleft group;    n = 132) or absence (control group;    n = 78). Group CL/P was subdivided according to the type of cleft: CL/P-I (cleft lip;    n = 35); CL/P-II (cleft lip and palate;    n = 45); CL/P-III (cleft palate;    n = 43); and CL/P-IV (rare orofacial clefts;    n = 9). Group CL/P had significantly more records on anemia ( p = .016) and fewer records on breastfeeding (P<.01) than controls. More records on anemia occurred in CL/P-II ( p = .004) and CL/P-IV ( p = .006) than the control group. The comparison among the orofacial cleft types regarding the anemia records showed no statistically significant differences ( p = .123). Group CL/P-I had more records on breastfeeding than the other cleft types ( p < .01). Conclusions Thus, it is suggested that the breastfeeding process is more complex, and the history of anemia is more frequent, in children with cleft lip and palate or rare orofacial clefts than in children without clefts.

scholarly journals A cross-sectional study of cardiac anomalies among children with orofacial cleft - role of echocardiography

2017 ◽  
Vol 4 (4) ◽  
pp. 1274
Author(s):  
R. Priyadharshini ◽  
Saji James ◽  
Jebaraj Rathinasamy ◽  
Mahalakshmi R. ◽  
Gautham Gopalakrishnan ◽  
...  
Keyword(s):  
Clinical Examination ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Cross Sectional Study ◽  
Cardiac Anomaly ◽  
Orofacial Cleft ◽  
Sectional Study ◽  
Orofacial Clefts ◽  
Cross Sectional ◽  
Cardiac Anomalies

Background: Orofacial cleft is one of the most common congenital facial abnormalities. Congenital heart disease (CHD) has been reported in up to 15% of the patients with orofacial clefts. Clinical cardiac examinations may sometime miss cardiac anomalies in children with orofacial clefts. The aim of our study is to find out CHD by echocardiography and to correlate this with clinical examination findings in children with orofacial clefts.Methods: In this cross-sectional study, 510 patients with orofacial clefts aged 1 month to 18 years were enrolled. History and clinical examination were performed and data entered in a pre-validated proforma. The type of orofacial cleft and syndromic features was specifically noted. Echocardiography was performed for all patients by a paediatric cardiologist and the clinical cardiovascular findings were correlated with the echocardiogram.Results: The commonest deformity was cleft lip and palate (69%), followed by isolated cleft palate (20.4%), and isolated cleft lip (10.6%). In our study population, 87.5% were non-syndromic and 12.5% were syndromic; 21.9% had cardiac anomaly, of which in 7.8% no cardiac defect was detected during systemic cardiovascular examination but their echocardiogram showed cardiac abnormality. This was statistically significant (p<0.000). Atrial Septal Defect was the commonest anomaly in both the groups. Pierre Robin Syndrome was found to be the commonest syndrome.Conclusions: The high prevalence of CHD among children with orofacial clefts in this study justifies the need for screening echocardiography because many times cardiac anomalies might not be detected in routine systemic examination. 

scholarly journals Genetic factors influencing risk to orofacial clefts: today’s challenges and tomorrow’s opportunities

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2800 ◽  
Author(s):  
Terri H. Beaty ◽  
Mary L. Marazita ◽  
Elizabeth J. Leslie
Keyword(s):  
Birth Defects ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Familial Aggregation ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Orofacial Clefts ◽  
Craniofacial Malformations ◽  
Genome Wide ◽  
The Right

Orofacial clefts include cleft lip (CL), cleft palate (CP), and cleft lip and palate (CLP), which combined represent the largest group of craniofacial malformations in humans with an overall prevalence of one per 1,000 live births. Each of these birth defects shows strong familial aggregation, suggesting a major genetic component to their etiology. Genetic studies of orofacial clefts extend back centuries, but it has proven difficult to define any single etiologic mechanism because many genes appear to influence risk. Both linkage and association studies have identified several genes influencing risk, but these differ across families and across populations. Genome-wide association studies have identified almost two dozen different genes achieving genome-wide significance, and there are broad classes of ‘causal genes’ for orofacial clefts: a few genes strongly associated with risk and possibly directly responsible for Mendelian syndromes which include orofacial clefts as a key phenotypic feature of the syndrome, and multiple genes with modest individual effects on risk but capable of disrupting normal craniofacial development under the right circumstances (which may include exposure to environmental risk factors). Genomic sequencing studies are now underway which will no doubt reveal additional genes/regions where variants (sequence and structural) can play a role in controlling risk to orofacial clefts. The real challenge to medicine and public health is twofold: to identify specific genes and other etiologic factors in families with affected members and then to devise effective interventions for these different biological mechanisms controlling risk to complex and heterogeneous birth defects such as orofacial clefts.

scholarly journals Maternal multivitamin intake and orofacial clefts in offspring: Japan Environment and Children's Study (JECS) cohort study

BMJ Open ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. e035817
Author(s):  
Satomi Yoshida ◽  
Masato Takeuchi ◽  
Chihiro Kawakami ◽  
Koji Kawakami ◽  
Shuichi Ito
Keyword(s):  
Cohort Study ◽  
Cleft Lip ◽  
Maternal Nutrition ◽  
Cleft Lip And Palate ◽  
Multinomial Logistic Regression ◽  
First Trimester ◽  
Secondary Outcome ◽  
Orofacial Cleft ◽  
Orofacial Clefts ◽  
Multivitamin Supplementation

ObjectivesOrofacial clefts are common birth defects with a lack of strong evidence regarding their association with maternal nutrition. We aimed to determine whether a relationship exists between maternal nutrient or multivitamin intake and orofacial clefts.DesignThis is a prospective, population-based nationwide cohort study.SettingThe study was conducted in 15 regional centres, consisting of local administrative units and study areas.ParticipantsA total of 98 787 eligible mother–child pairs of the Japan Environment and Children’s Study were included.InterventionExposures were maternal nutrition and the use of supplemental multivitamins in mothers.Primary and secondary outcome measuresOutcomes were the occurrence of any orofacial cleft at birth. Multinomial logistic regression analyses were used to evaluate the association between maternal multivitamin intake and the incidence of orofacial clefts.ResultsOf the 98 787 children, 69 (0.07%) were diagnosed with cleft lip alone, 113 (0.11%) were diagnosed with cleft lip and palate, and 52 (0.05%) were diagnosed with cleft palate within 1 month after birth. Regarding the total orofacial cleft outcome, statistically significant point estimates of relative risk ratios (RR) were determined for multivitamin intake before pregnancy (RR=1.71; 95% CI 1.06 to 2.77) and during the first trimester (RR=2.00; 95% CI 1.18 to 3.37), but the association was not significant for multivitamin intake after the first trimester (RR=1.34; 95% CI 0.59 to 3.01). Maternal micronutrient intake via food was not associated with the incidence of orofacial clefts in offspring.ConclusionsIntake of multivitamin supplements shortly before conception or during the first trimester of pregnancy was found to be associated with an increased incidence of orofacial clefts at birth. Pregnant women and those intending to become pregnant should be advised of the potential risks of multivitamin supplementation.

scholarly journals Immediate rehabilitation with feeding appliance of a three day old neonate with cleft lip and palate- a case report

2017 ◽  
Vol 13 (2) ◽  
pp. 293-295
Author(s):  
Deepika Kapoor ◽  
Deepanshu Garg
Keyword(s):  
Case Report ◽  
Cleft Lip ◽  
Multidisciplinary Approach ◽  
Cleft Lip And Palate ◽  
Facial Growth ◽  
Orofacial Clefts ◽  
High Incidence ◽  
Negative Effect ◽  
Growth Development ◽  
Very High

Orofacial clefts (OFC) are one of the most common congenital problems seen with a very high incidence. It imparts a negative effect on the overall health of the child by hindering in his feeding practices, normal facial growth, development of dentition and hence speech. Infants born with orofacial clefts have oronasal communication which creates a problem with the creation of negative pressure inside the oral cavity required for suckling.The treatment for such patients is with the multidisciplinary approach but the preliminary  concern for the neonate is to help with the feeding for which a feeding appliance is given. This case report presents a case of a 3-day old infant to whom a feeding appliance was given to aid in suckling. 

scholarly journals Case–Parent Trio Studies in Cleft Lip and Palate

2020 ◽  
Vol 07 (03) ◽  
pp. 075-079
Author(s):  
Mahamad Irfanulla Khan ◽  
Prashanth CS
Keyword(s):  
Genetic Variants ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Association Studies ◽  
Geographical Location ◽  
Genetic Association Studies ◽  
Population Based ◽  
Genome Wide Association Studies ◽  
Family Based ◽  
Study Designs

AbstractCleft lip with or without cleft palate (CL/P) is one of the most common congenital malformations in humans involving various genetic and environmental risk factors. The prevalence of CL/P varies according to geographical location, ethnicity, race, gender, and socioeconomic status, affecting approximately 1 in 800 live births worldwide. Genetic studies aim to understand the mechanisms contributory to a phenotype by measuring the association between genetic variants and also between genetic variants and phenotype population. Genome-wide association studies are standard tools used to discover genetic loci related to a trait of interest. Genetic association studies are generally divided into two main design types: population-based studies and family-based studies. The epidemiological population-based studies comprise unrelated individuals that directly compare the frequency of genetic variants between (usually independent) cases and controls. The alternative to population-based studies (case–control designs) includes various family-based study designs that comprise related individuals. An example of such a study is a case–parent trio design study, which is commonly employed in genetics to identify the variants underlying complex human disease where transmission of alleles from parents to offspring is studied. This article describes the fundamentals of case–parent trio study, trio design and its significances, statistical methods, and limitations of the trio studies.

Morphological Presentation of Orofacial Clefts: An Epidemiological Study of 5004 Patients in a Tertiary Care Hospital of Central India

2021 ◽  
pp. 105566562110577
Author(s):  
Jaideep Singh Chauhan ◽  
Sarwpriya Sharma
Keyword(s):  
Cleft Palate ◽  
Epidemiological Study ◽  
Cleft Lip ◽  
Cleft Lip And Palate ◽  
Tertiary Care ◽  
Central India ◽  
Care Hospital ◽  
Orofacial Clefts ◽  
Chi Square ◽  
The Right

Objective: To analyse the morphological presentation of orofacial clefts, gender, syndromes and systemic anomalies associated with them. Design: This was an epidemiological study performed in the patients who were registered for cleft lip and palate surgeries in our centre. The data was evaluated both retrospectively as well as prospectively. Patients/ Participants: The patients registered from November 2006 to April 2021 were studied. Out of 5276 patients, data of 5004 cases were analysed, rest 272 patients were excluded due to lack of information. Statistical analysis and Chi square test were applied. Results: Cleft deformities were more common in males than females. Cleft lip with palate was the commonest phenotype (52.2%). It was followed by isolated cleft lip (22.9%), isolated cleft palate (22.1%), rare clefts (1.62%) and syndromic clefts (1.18%). Unilateral variants were more frequent than bilateral. In unilateral, left side was more common than the right side. Among bilateral, most of the cases had premaxillary protrusion. In the present study, 3.46% of all the patients had associated anomalies affecting their other organs. Less common cleft phenotypes like microform cleft lip and submucous cleft palate ± bifid uvula showed frequency of 0.62% and 0.64% respectively. Conclusion: Thorough examination of cleft deformity should be done as it may appear as an isolated deformity or part of a syndrome and have associated systemic anomalies. This may help us to deliver comprehensive care to the patients and can prevent potential operative complications.

scholarly journals Atuação Fonoaudiológica e Fisioterápica nas Fissuras Orofaciais não Sindrômicas

UNICIÊNCIAS ◽  
2021 ◽  
Vol 24 (2) ◽  
pp. 205-210
Author(s):  
Carla Meliso Rodrigues Silvestre ◽  
Ana Clara Giraldeli ◽  
Luana Borges Estevão ◽  
Eliane Gomes Fernandes de Oliveira ◽  
Cristhiane Almeida Leite da Silva ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Cleft Lip ◽  
Speech Therapy ◽  
Cleft Lip And Palate ◽  
Functional Independence ◽  
Oral Feeding ◽  
Orofacial Clefts ◽  
Long Term Treatment ◽  
Speech Therapist

A fissura de lábio e ou de palato não sindrômicas são anomalias congênitas craniofaciais mais frequentes. Elas ocasionam problemas estéticos e funcionais que requerem tratamento em longo prazo, envolvendo reabilitação multidisciplinar incluindo a fonoaudiologia e fisioterapia. Este estudo propõem apresentar alguns dos princípios de atuação do fonoaudiólogo e do fisioterapeuta nas fissuras orofaciais não sindrômicas. Realizou-se uma revisão de literatura narrativa com busca na Bireme e Scielo e nas bases Lilacs, Pedro e  PubMed em outubro de 2020, envolvendo a atuação do  fonoaudiólogo e do fisioterapeuta nas fissuras orofaciais não sindrômica, no idioma inglês e português, sem recorte temporal. Os estudos encontrados observaram que a intervenção fonoaudiológica e fisioterapêutica deve ser mais precoce e de acordo com a disfunção apresentada. De modo geral, a atuação do fonoaudiólogo favorece a alimentação oral  e o desenvolvimento global referente à linguagem, a fala, audição e neuropsicomotor, para evitar atrasos e favorecer o melhor desenvolvimento infantil. A atuação fisioterapêutica visa diminuir a hospitalização prolongada, melhorar a qualidade de vida e funcionalidade, bem como assistir as crianças que cursarem com problemas motores, posturais e respiratórios. Conclui-se que a atuação fonoaudiológica nas diferentes fases da reabilitação de indivíduos com fissuras labiopalatinas contribui para alimentação e inteligibilidade da fala, beneficiando assim a comunicação verbal e consequentemente a interação com o meio social; e a assistência fisioterapêutica ajuda e melhorar a sintomatologia e as disfunções respiratórias apresentadas, prevenindo e tratando complicações de forma a melhorar a qualidade de vida e restabelecer a independência funcional.   Palavras-chave: Fissura Palatina. Fenda Labial. Aleitamento Materno. Fala. Fisioterapia.   Abstract Non-syndromic cleft lip and or palate are the most frequent congenital craniofacial anomalies. They cause aesthetic and functional problems that require long-term treatment, involving rehabilitation including speech therapy and physiotherapy. This study proposes to present some of the principles of performance of the speech therapist and physiotherapist in non-syndromic orofacial clefts. A narrative literature review was carried out with searches in Bireme and Scielo and in the Lilacs, Pedro and PubMed databases in October 2020, involving the performance of the speech therapist and physiotherapist in non-syndromic orofacial clefts, in English and Portuguese, with no time frame. The studies observed that speech therapy and physiotherapy intervention should be as earlier and in accordance with the presented dysfunction. In general, the performance of the speech therapist favors oral feeding and the global development related to language, speech, hearing and neuropsychomotor, to avoid delays and favor best child development. Physiotherapeutic action aims to reduce the prolonged hospitalization, improve quality of life and functionality, as well as assist children who are experiencing motor, postural and respiratory problems. It is concluded that the speech therapy performance in the different phases of rehabilitation of individuals with cleft lip and palate contributes to feeding and speech intelligibility, thus benefiting verbal communication and consequently the interaction with the social environment; and physiotherapeutic assistance helps and improves the symptoms and respiratory disorders presented, preventing and treating complications in order to improve the quality of life and restore functional independence.   Keywords: Cleft Palate. Cleft Lip. Breast Feeding. Speech. Physiotherapy.

Surgical Repair of Orofacial Clefts in North Kivu Province of Eastern Democratic Republic of Congo (DRC)

2020 ◽  
Vol 57 (11) ◽  
pp. 1314-1319
Author(s):  
Luc Malemo Kalisya ◽  
Jacques Fadhili Bake ◽  
Bake Elisee ◽  
Kavira Nyavandu ◽  
Robert Perry ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Democratic Republic ◽  
Cleft Lip And Palate ◽  
Surgical Repair ◽  
Democratic Republic Of Congo ◽  
Orofacial Clefts ◽  
Republic Of Congo ◽  
General Surgeons ◽  
North Kivu

Background: There is a high prevalence of orofacial clefts in low- and middle-income countries with significant unmet need, despite having 50% of the population younger than 18 years in countries such as the Democratic Republic of Congo (DRC). The purpose of this article is to report on the experience of general surgeons with orofacial clefts at a single institution. Methods: This is a retrospective study of patients treated for cleft lip/palate in the province of North Kivu, DRC between 2008 and 2017. Results: A total of 1112 procedures (122/year) were performed. All procedures were performed by general surgeons following training by an international nongovernmental aid organization. A total of 59.2% of patients were male and the median age was 3.4 years (interquartile range: 0.7-13 years). Average distance from surgical center to patient location was 242.6 km (range: 2-1375 km) with outreach performed for distances >200 kms. A majority (82.1%) of patients received general anesthesia (GA) with significant differences in use of GA, age, weight, and length of stay by major orofacial cleft category. Of the 1112 patients, 86.1% were reported to have cleft lip alone, 10.5% had cleft lip and palate, and 3.4% cleft palate alone. Despite this, only 5.3% of patients underwent surgical repair of cleft palate. Conclusions: Multiple factors including malnutrition, risk of bleeding, procedural complexity, and cosmetic results may contribute to the distribution of procedures performed where most cleft palates are not treated. Based on previously published estimates, unmet needs and social burden of cleft lip and palate are high in the DRC.

scholarly journals Epigenome-Wide Association Study Using Prediagnostic Bloods Identifies New Genomic Regions Associated With Pancreatic Cancer Risk

2020 ◽  
Vol 4 (5) ◽  
Author(s):  
Dominique S Michaud ◽  
Mengyuan Ruan ◽  
Devin C Koestler ◽  
Dong Pei ◽  
Carmen J Marsit ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Dna Methylation ◽  
Study Design ◽  
Peripheral Blood ◽  
Association Studies ◽  
Gene Set Enrichment Analysis ◽  
Blood Collection ◽  
Blood Draw ◽  
Genomic Regions ◽  
Prospective Study Design

Abstract Background Epigenome-wide association studies using peripheral blood have identified specific sites of DNA methylation associated with risk of various cancers and may hold promise to identify novel biomarkers of risk; however, few studies have been performed for pancreatic cancer and none using a prospective study design. Methods Using a nested case-control study design, incident pancreatic cancer cases and matched controls were identified from participants who provided blood at baseline in 3 prospective cohort studies. DNA methylation levels were measured in DNA extracted from leukocytes using the Illumina MethylationEPIC array. Average follow-up period for this analysis was 13 years. Results Several new genomic regions were identified as being differentially methylated in cases and controls; the 5 strongest associations were observed for CpGs located in genes TMEM204/IFT140, MFSD6L, FAM134B/RETREG1, KCNQ1D, and C6orf227. For some CpGs located in chromosome 16p13.3 (near genes TMEM204 and IFT140), associations were stronger with shorter time to diagnosis (eg, odds ratio [OR] = 5.95, 95% confidence interval [CI] = 1.52 to 23.12, for top vs bottom quartile, for &lt;5 years between blood draw and cancer diagnosis), but associations remained statistically significantly higher even when cases were diagnosed over 10 years after blood collection. Statistically significant differences in DNA methylation levels were also observed in the gastric secretion pathway using Gene Set Enrichment Analysis (GSEA) analysis. Conclusions Changes in DNA methylation in peripheral blood may mark alterations in metabolic or immune pathways that play a role in pancreatic cancer. Identifying new biological pathways in carcinogenesis of pancreatic cancer using epigenome-wide association studies approach could provide new opportunities for improving treatment and prevention.

Sign in / Sign up

Export Citation Format

Share Document