Variant analyses of candidate genes in orofacial clefts in multi-ethnic populations.

OBJECTIVES: Cleft lip with/without cleft palate and cleft palate only is congenital birth defects where the upper lip and/or palate fail to fuse properly during embryonic facial development. Affecting ~1.2/1000 live births worldwide, these orofacial clefts impose significant social and financial burdens on affected individuals and their families. Orofacial clefts have a complex etiology resulting from genetic variants combined with environmental covariates. Recent genome-wide association studies and whole-exome sequencing for orofacial clefts identified significant genetic associations and variants in several genes. Of these, we investigated the role of common/rare variants in SHH, RORA, MRPL53, ACVR1, and GDF11. MATERIALS AND METHODS: We sequenced these five genes in 1255 multi-ethnic cleft lip with/without palate and cleft palate only samples in order to find variants that may provide potential explanations for the missing heritability of orofacial clefts. Rare and novel variants were further analyzed using in silico predictive tools. RESULTS: Ninteen total variants of interest were found, with variant types including stop-gain, missense, synonymous, intronic, and splice-site variants. Of these, 3 novel missense variants were found, one in SHH, one in RORA, and one in GDF11. CONCLUSION: This study provides evidence that variants in SHH, RORA, MRPL53, ACVR1, and GDF11 may contribute to risk of orofacial clefts in various populations.

Mutations in Van Der Woude Families From Ethiopia.

BACKGROUND: Van der Woude syndrome (VWS) is the most common syndromic orofacial cleft which accounts for approximately 2% of all cleft lip (CL) and/or palate cases. It is characterized by the presence of lower lip pits, in addition to CL, CL with or without cleft palate, cleft palate only, and hypodontia. It is inherited as an autosomal-dominant trait with almost complete penetrance but variable expressivity, and different variants in IRF6 gene have been reported in different populations around the world including African populations (Ethiopian, Ghanaian, and Nigerian). METHODS AND FINDINGS: The authors investigated the role of IRF6 in Ethiopian families with VWS. The DNA of 7 families with VWS from Ethiopia were screened by Sanger sequencing. The authors screened all 9 exons of IRF6 and found a novel missense variant in exon 4 (p. Gly65Glu). This variant was predicted to be deleterious/probably damaging by Sift and PolyPhen, respectively. The IRF6 variant (p. Gly65Glu) segregates in the family since it was identified in the father and a sibling. CONCLUSION: Several of the individuals with lower lip pits in this study did not seek treatment. This is due to lack of awareness about the significance of this minor looking deformity and its consequences, and availability of treatment for birth defects. Therefore, it is important to educate families. Finally, screening for novel variants in known genes has a role in counseling and prenatal diagnosis for high-risk families.

Assessing the Practice of Birth Defect Registration at Addis Ababa Health Facilities.

BACKGROUND: Birth defects are conditions that exist at birth and cause structural changes in one or more parts of the body. In order to plan proper management and design preventive activities of these conditions, accurate tracking, registration and analyses of the registered data are important. We assessed the practice of birth defect registration at Addis Ababa health facilities. METHODS: We retrospectively checked the existence of a separate birth defect registry book and assessed the delivery room registration book for completeness in registering birth defects. We also assessed the total number of birth defects registered during 2010-2015. RESULTS: We assessed the practice of birth defect registration at 37 delivery service providing health facilities in Addis Ababa, 20 public and 17 private institutions. Of the 37 health institutions assessed, 23 registered birth defects (3 of them used a separate birth defect registry books, and 20 used a regular registration book to register birth defects). The remaining 14 did not register any congenital anomaly. Of the institutions that do not register congenital anomalies, 10 are private and four are public. CONCLUSION: Only three delivery providing health facilities had a dedicated birth defect registry book which is close to ideal for a birth defect registration. There is a need for others to do the same until an electronic birth defect registration is established. This registration will serve as a resource for clinical governance and studies into quality of life, quality of care, etiology and prevention.

The Role of Environmental Factors in the Etiology of Nonsyndromic Orofacial Clefts.

BACKGROUND: Nonsyndromic orofacial clefts (NSOFCs) represent the most common congenital anomalies in the head and neck region. Multiple factors contribute to the occurrence of this anomaly. The etiology of NSOFCs in the Ethiopian population has not been investigated prior to this study. AIMS OF THE STUDY: To assess the role of maternal environmental factors in the occurrence of NSOFCs in the Ethiopian Population. METHODS: The authors used unmatched case control study design and evaluated the role of environmental factors to the occurrence of NSOFCs in the Ethiopian population. The participants were recruited from the same institution (Yekatit 12 Hospital Medical College). The authors studied 760 mothers (359 mothers of children born with NSOFCs and 401 mothers of children born without any congenital anomalies). Univariate and multivariate logistic regression analyses were used to calculate relative risk by odds ratio and 95% confidence interval. RESULTS: Mothers who gave history of bronchial asthma and mothers who were admitted for threatened abortion had a higher risk of delivering a child with NSOFCS P value=0.013; AOR=0.194, 95% CI [0.053-0.712], P value <0.001; AOR= 0.179, 95% CI [0.091-0.352] respectively. Higher number of children with NSOFCs were born to mothers who were exposed to diagnostic X-ray investigation during early pregnancy than those who were not exposed P value 0.048; AOR=0.375, 95% CI [0.142-0.990]. CONCLUSION: Maternal exposure to diagnostic x-ray, maternal chronic illness like bronchial asthma and threatened abortion were found to be associated with the occurrence of NSOFCS in the studied population.

Oral Health-Related Quality of Life of Children Born With Orofacial Clefts in Ethiopia and Their Parents.

OBJECTIVE: To assess the oral health-related quality of life (OH-RQoL) using a translated standardized measure in an understudied population of Ethiopian children born with orofacial clefts (OFCs) and their parents. METHODS: Using a descriptive study design, we assessed the OH-RQoL of 41 patients with OFCs between the ages of 8 and 17 years and their parents. Participants received multidisciplinary cleft care from 2008 to 2016. They completed an Amharic translation of the Child Oral Health Impact Profile (COHIP). RESULTS: There was strong internal reliability with the translated COHIP for parents and patients. Parents' COHIP scores ranged from 67 to 186, and patients' scores were 78 to 190. The mean for patients and parents was 155, indicating good OH-RQoL. CONCLUSION: The Amharic translation of the COHIP appears appropriate for use with families in Ethiopia. Both parents and patients reported OH-RQoL at similar levels as other international populations.

Descriptive Epidemiology of Orofacial Clefts in Ethiopia.

BACKGROUND: The prevalence of birth defects including orofacial clefts (OFC) in Ethiopia is not known and there is no established birth defects registration system. OBJECTIVES: To investigate the prevalence and incidence of OFC in Ethiopia. DESIGN: Retrospective hospital-based descriptive study. METHODS: The authors obtained data from the Smile Train database on Ethiopian patients with OFC who underwent surgical treatment from June 2007 to December 2013 at 31 hospitals distributed throughout the country. Data related to live births in Ethiopia during the mentioned period were obtained from the Federal Ministry of Health database for estimates of the incidence and prevalence rates. RESULTS: The total number of life births during the study period was 18,811,316. During this same period, 18,073 cleft patients approximately ranging from 1 to 75 years old were examined and treated at the hospitals mentioned earlier. The incidence rate estimated from the total number of affected children during the study period (N = 8232) is 0.44/1000 live births. The prevalence rate is 0.20/1000 and this was estimated using the number of total population in 2013 (N = 88,703,914). There is a significant difference in frequency between bilateral clefts of the lip and/or palate (CLP) (26.9%) versus unilateral CLP (73.1%) (P < 0.0001). There is also a significant difference in frequency between bilateral cleft lips only (15.4%) versus unilateral cleft lip only (84.6%), P < 0001. CONCLUSION: It is obvious that the findings in this study cannot be representative of the true picture but provides a previously unavailable national estimate of incidence and prevalence of OFC in Ethiopia. It can also be used as comparison for future community-based studies.