Analysis of Consanguinity as Risk Factor of Nonsyndromic Cleft Lips with or without Palate

Abstract

Objectives The etiologies of nonsyndromic cleft lips with or without palate (NS CL/P) are multifactorial, which include consanguineous marriages. The incidence of NS CL/P is relatively high in Indonesia notably in one of Indonesia's tribes whose members frequently marry close cousins. Thus, the purpose of this study is to analysis consanguinity as risk factor of NS CL/P in Sasak tribe, East Lombok, Indonesia

Materials and Methods An observational analysis was made of a collected database of NS CL/P patients treated in social services in regency hospital of Dr. Soejono Selong, East Lombok, Indonesia. Demographic data such as age, gender, address (urban/rural), parent's education, presence or absence of consanguinity, type of clefts, and a three-generation pedigree were collected by interview and hospital medical record. Before analysis, patient information was anonymized and deidentified. From 2016 to 2018, each of 100 cleft and normal subjects with their Sasak parent were audited. The risk factors were analyzed statistically using odds ratio (OR) and chi-squared test.

Results Consanguineous marriages identified 54 cases (54%), and 10 cases (10%) out of a total each 100 NS CL/P and controls, respectively. The majority of consanguinity (53.7%) was discovered in marriages between first cousins. NS CL/P cases were statistically linked (p = 0.00) with consanguineous marriages (OR: 10; 95% confidence interval: 1.6–3.1); in which the most prevalent case is unilateral cleft lips.

Conclusion Consanguineous marriage increases the risk of NS CL/P in Sasak tribe, East Lombok, Indonesia. The development of strategies to educate communities on the impacts of culture-consanguineous marriage is required. The genetic inheritance from their ancestor may be responsible for the increased incidence of NS CL/P.

Keywords

consanguinity - cleft lips - cleft palate

Authors' Contribution

Y.S.R. investigated and designed the study, analyzed the data, conducted the experiment and collected the results, and wrote and revised the manuscript. S.H. conducted a measuring investigation. S.C. reviewed the data and the manuscript. I.R.H. reviewed the data and the manuscript, and revised the manuscript for publication. S.F.-M. and S.M.H.F. analyzed the data and drafted the manuscript and revised the manuscript for the publication.

Publication History

Article published online:
23 November 2023

• References

• 1 Khamila N, Nurwiadh A, Putri FA. Characteristic of cleft lip and palate at cleft center of Padjadjaran University Dental Hospital: 2 years retrospective study. Jurnal Pendidikan Tambusai 2022; 6 (01) 1058-1064
• 2 Sosiawan A, Kurniati M, Danudiningrat CP, Wahjuningrum DA, Mulyawan I. The role of family history as a risk factor for non-syndromic cleft lip and/or palate with multifactorial inheritance. Dent J (Majalah Kedokteran Gigi) 2021; 54 (02) 108-112
• 3 Romdhane L, Mezzi N, Hamdi Y, El-Kamah G, Barakat A, Abdelhak S. Consanguinity and inbreeding in health and disease in North African populations. Annu Rev Genomics Hum Genet 2019; 20: 155-179
• 4 Erwinsya E, Handoyo E, Arsal T. Merariq tradition of Sasak tribe in social construction and national law. J Education Social Studies 2020; 9 (01) 48-55
• 5 AlHammad Z, Suliman I, Alotaibi S. et al. The prevalence of non-syndromic orofacial clefts and associated congenital heart diseases of a tertiary hospital in Riyadh, Saudi Arabia. Saudi Dent J 2021; 33 (03) 137-142
• 6 Silva CM, Pereira MCM, Queiroz TB, Neves LTD. Can parental consanguinity be a risk factor for the occurrence of nonsyndromic oral cleft?. Early Hum Dev 2019; 135: 23-26
• 7 Ahmed Sakran K, Mutahar Abotaleb B, Khaled Al-Rokhami R. et al. Analysis of environmental exposures for nonsyndromic cleft lip and/or palate: a case-control study. Iran J Public Health 2022; 51 (03) 578-586
• 8 Hardiayanti A. Operasi Bibir Sumbing Gratis di NTB bersama Rereq. 2019 [30 Jaunari 2019]; Available at: https://andyhardiyanti.com/2019/01/lombok-rereq/
• 9 Yu Y, Yao J. . Classification of Cleft Lip and Palate. (eds) Atlas of Cleft Lip and Palate & Facial Deformity Surgery. 2020. Springer; Singapore: https://doi.org/10.1007/978-981-15-4419-4_1
• 10 Paganini A, Moss T, Persson M, Mark H. A gender perspective on appearance-related concerns and its manifestations among persons born with unilateral cleft lip and palate. Psychol Health Med 2021; 26 (06) 771-778
• 11 Pool SMW, der Lek LMV, de Jong K, Vermeij-Keers C, Mouës-Vink CM. Embryologically based classification specifies gender differences in the prevalence of orofacial cleft subphenotypes. Cleft Palate Craniofac J 2021; 58 (01) 54-60
• 12 Impellizzeri A, Giannantoni I, Polimeni A, Barbato E, Galluccio G. Epidemiological characteristic of orofacial clefts and its associated congenital anomalies: retrospective study. BMC Oral Health 2019; 19 (01) 290
• 13 Lehtonen V, Anttonen V, Ylikontiola LP, Koskinen S, Pesonen P, Sándor GK. Dental anomalies associated with cleft lip and palate in Northern Finland. Eur J Paediatr Dent 2015; 16 (04) 327-332
• 14 Saeed OB, Moore MG, Zawahrah H, Tayem M, Kavoosi T, van Aalst JA. The influence of consanguinity on familial clefting among Palestinians. Cleft Palate Craniofac J 2019; 56 (08) 1072-1079
• 15 Begum G. Repercussions of consanguinity on metrical traits at different phases of growth. J Clin Diagn Res 2023; 17 (02) LC01-LC09
• 16 Soheilirad Z. What should be the focus of counseling in parental consanguinity: genetic disorders or underlying beliefs. Egypt J Med Hum Genet 2020; 21: 8
• 17 Sadiq H, Ijaz R, Ayub A. Patterns of orofacial clefts and associated risk factors in Pakistan: an institutional experience. J Cleft Lip Palate Craniofacial Anomalies 2022; 9 (02) 145-150
• 18 El Goundali K, Chebabe M, Zahra Laamiri F, Hilali A. The determinants of consanguineous marriages among the Arab population: a systematic review. Iran J Public Health 2022; 51 (02) 253-265
• 19 Khan MI, Cs P, Srinath NM. Genetic factors in nonsyndromic orofacial clefts. Glob Med Genet 2020; 7 (04) 101-108
• 20 Kurniati M, Pramono DRM, Sosiawan A, Tirtaningsih NW. The genetic aspect of non-syndromic cleft lip and palate towards candidate genes in the etiology: a literature review. Indian J Forensic Med Toxicol 2021; 15 (03) 3604-3608
• 21 Slavec L, Karas Kuželički N, Locatelli I, Geršak K. Genetic markers for non-syndromic orofacial clefts in populations of European ancestry: a meta-analysis. Sci Rep 2022; 12 (01) 1214
• 22 Galván-Femenía I, Barceló-Vidal C, Sumoy L, Moreno V, de Cid R, Graffelman J. A likelihood ratio approach for identifying three-quarter siblings in genetic databases. Heredity 2021; 126 (03) 537-547
• 23 Anwar S, Taslem Mourosi J, Arafat Y, Hosen MJ. Genetic and reproductive consequences of consanguineous marriage in Bangladesh. PLoS One 2020; 15 (11) e0241610
• 24 Abbas B, Abbas S, Malik SM, Rahim M, Umair M, Khurshid Z. Consanguineous marriages and dental anomalies: a cross-sectional analytical study. Int J Dentistry 2022;9750460;
• 25 Mortreux J, Busa T, Germain DP. et al. The role of CNVs in the etiology of rare autosomal recessive disorders: the example of TRAPPC9-associated intellectual disability. Eur J Hum Genet 2018; 26 (01) 143-148
• 26 Rochmah YS, Suwarsi L, Harumsari S, Sosiawan A, Muis SF, Faradz SMH. Maternal polymorphism MTHFR A1298C not C677T and MSX1 as the risk factors of non-syndrome cleft lips /palate in Sasak tribe Indonesia. J Int Dental Med Res 2018; 11 (01) 120-123
• 27 Jaruga A, Ksiazkiewicz J, Kuzniarz K, Tylzanowski P. Orofacial cleft and mandibula prognathism human genetics and animal models. Int J Mol Sci 2022; 23: 953
• 28 Vieira AR, Furtado P, Filho VVL. et al. Orofacial cleft frequency differences depending on geographic origin: coast vs. inland. Front Dent Med 2021; 2: 670948