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Consanguineous marriages increase risk of congenital anomalies-studies in four generation of an afghan family.

Nommanudien Naibkhil, Ekta Chitkara*
Department of Applied Medical Science, Lovely Professional University, Phagwara, Punjab, India.
Corresponding Author: Ekta Chitkara, Department of Applied Medical Science, Lovely Professional University, Punjab, India.
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Consanguineous marriage is a common and preferable custom of marriage among Afghans. Consanguineous marriage may cause transfer of two recessive defective alleles, one from the mother and the other from the father, to offsprings; which may cause appearance of congenital anomalies. Four generation of an Afghan family, residing in Afghanistan, and in which consanguineous and non-consanguineous marriages are practiced, were studied in this article. Out of 14 marriages, 7 were consanguineous and 7 non-consanguineous. Out of the offsprings of consanguineous marriages 52.3% presented congenital anomalies while among the generations of non-consanguineous parent no considerable congenital anomaly was observed.


Consanguineous marriages, Non-consanguineous marriage, Congenital anomalies, Pedigree.


Consanguineous marriage is referred to a marital union among close biological kin. In clinical genetics, it is called the relationship by marriage between first and second cousins [1]. Consanguineous marriage is most common in the Middle East, West Asia and North Africa [2,3]. Rate of consanguineous marriage in different countries are dependent on different factors like education level, religion, local tradition, and socio-economic status [4,5]. Studies over several decades have shown that there is a high correlation between consanguineous marriage and inherited congenital malformation [6].
Some of inherited genetic disorders are transferred as autosomal recessive in carrier individuals and consanguinity facilitates homozygosity mapping of these genetic disease; which appears in their offspring as congenital anomalies (disease, disorder or defect) [6].
Congenital anomalies (CA) are the structural or functional anomalies (including metabolic disorders); which are present during birth of the child. These abnormalities can be isolated or seen as part of a syndrome; which results morbidity and mortality of neonates and infants [7,8]. Based on the WHO (world Health Organization) report, 3% of newborns are associated with CA equals to approximately 3 million fetuses and infants per year [9]. CAs vary from country to country; with lowest rate in Japan (1.07%) and highest rate in Taiwan (4.3%) [10]. Social, racial, ecological, and economical issues may have a role in the rate variation [10, 11].
Congenital anomalies can lead to infant mortality and it has been seen that more than 70% of such infants die in the first month of birth [12-15]. Etiology shows that 30-40% of congenital malformation is genetic [16]. One of the major factors contributing to the increased risk of congenital malformation and infant mortality is consanguineous marriage [17-19].
The offsprings of consanguineous parents are at a risk of a host of disease like cancer, mental disorders, hypertension, hearing deficit, diabetes mellitus, epilepsy, asthma, leukemia [6], beta thalassemia [20], congenital and noncongenital heart diseases [21].
In Afghanistan, like many other countries, parents usually find spouses for their children. Due to socioeconomic conditions selection of spouse is sometimes very difficult. Hence, someone well known and having the qualities of joining their families is preferred. Therefore, consanguineous marriages are preferred and the first cousin is the first choice. Over several generations consanguineous relationships become closer and complicated.

Materials and Methods

This study includes the pedigree of 4 generation of an Afghan family to observe the effect of consanguineous and non-consanguineous marriages on their offspring. Data collection was done through questionnaires and interviews. Questionnaires were made in Dari language and included relationship between couples (consanguineous or nonconsanguineous), age of marriage, addiction to any drug, and use of alcohol during pregnancy (Table 1). Same questions are asked in the case of interviews.
Four generations of an Afghan family are studied here. As showed in Figure 1, Pedigree Chart, first generation (G1); is a male and female married as consanguineous marriage (father's side cousins). Generation 2, the offsprings of the G1, consisted of 8 individuals (5 M and 3 F). G3: the offsprings of the G2; with 40 individuals (27 M and 13 F), and G4: the offsrpings of G3; including 22 individuals (11 M and 11 F). The 4th generation members are still single, some of them are not in the age of marriage and some of them will marry in the close future.
Consanguinity rate
Out of 14 marriages, 7 (50%) are consanguineous marriages and 7 (50%) are non-consanguineous marriage (Table 2).


Fourteen marriages tool place among member this family, out of which 7 are consanguineous. At least 2 children from each consanguineous marriage have congenital anomalies. Offspring of one consanguineous parent didn't show any considerable congenital anomalies yet, as these children are still very young. School performance, height and other non-congenital diseases; which demonstrate the effect of consanguineous marriage, are not yet evident. Out of 44 offspring from consanguineous parents, 23 individuals (19 males & 4 females) equal to 52.3%, have considerable congenital anomalies or died within first month of birth as result of congenital anomalies. Among 26 individuals (13 M and 13 F) from non-consanguineous parents, no considerable congenital anomaly has been seen (Figure 1). Out of 23 individuals with congenital anomalies, 2 have hearing deficit, 2 show low school performance or very low IQ, 15 died within the first month of birth, 2 have Cerebral Palsy (CP) and 2 have kyphosis (Table 3).


This study is conducted to show effects of consanguineous marriages versus non-consanguineous marriages on their offspring, in those people who are very close and have high similarities in heredity, life style, socio-economic status, environment, nutrition, and history of disease. As other factors like hereditary, age of parents [22], addiction to narcotics, other drug abuse, etc., may also have a role in the development of congenital anomalies and hence may interfere on consanguinity study we preferred to study consanguineous marriage effects in a different generation of family in which consanguineous and nonconsanguineous marriages are equally practiced. The main impact of consanguineous marriage is an elevation in the rate for homozygotes in recessive disorders [23-25]. If a new mutation is inserted in such a population, it will spread rapidly and lead to an elevation in carries' prevalence and an increased number of affected homozygous individuals [26]. It is believed, but has not been proved yet, that high inbreeding rates through several generations may removes deleterious recessive genes from the gene pool [24].
Studies from India (South India), where for more than 2,000 years inbreeding is practiced, show no appreciable elimination of recessive lethal and sublethal genes from the gene pool [27]. The highest rate of congenital malformation and genetic disorders with more than 65 affected children per 1,000 live births is reported in the Eastern Mediterranean region as compared to Europe, Australia and North America with 52/1,000 live births [28]. Consanguinity rate can be defined in to four major areas: 1) Regions with <1% consanguineous marriages (consanguineous marriage beyond the second cousins may exist f<0.0156), e.g., North America, Australasia and most of Europe, 2) Regions with 1-10% of consanguineous marriage e.g., Japan, South America and the Iberian Peninsula, 3) Regions with 20-50% of consanguineous marriages e.g., North Africa, much of west, Central, and South Asia, and 4) The highest rate of consanguineous marriages e.g., Pondicherry, South India [29], where 54.9% consanguineous marriages have been recorded which is equivalent to mean coefficient of inbreeding of a=0.044, and among army families in Pakistan where the percentage of consanguineous marriage percentage is 77.1% (a=0.0414) [30]. Consanguineous marriage percentage in 6 north provinces of Afghanistan including Kabul shows 46.2%. [31], and in Afghan refugees in Pakistan shows 55.4% [32]. Till date there are no confirmed studies to shows consanguinity rate and related congenital anomalies in Afghanistan. Our next study will include a larger population with congenital anomalies to show its relationship with consanguinity.
The prevalence of consanguineous marriages is above 50% in Muslim countries of the Middle East, Pakistan and Afghanistan, but there is no specific guidance in the Holy Qur'an that could be interpreted as encouraging consanguineous marriages [33]. Indeed, according to one of the hadiths, recorded pronouncements of the Prophet Mohammad (PBUH), cousin marriages were best discouraged. So, it is traditional and socially practice taken up by Muslim countries.
In a multi-national study, that was performed recently, to estimate the mortality rate, pre- puberty deaths of first cousin offspring show 4.4% higher value than nonconsanguineous unions, in over 600,000 pregnancies and live births [34]. The high mortality rate in developing countries, associated with consanguinity, largely occurs within the first year of birth [35-38]. In most of the cases the exact cause of death is not cleared because of the unavailability of proper diagnostic facilities, and lack of initiative of parents to sanction prenatal diagnosis or autopsy examinations. An obvious correlation between consanguinity and autosomal recessive disease was evident where the diagnosis was possible [27, 39-42]. Several deaths have also been reported in a proportion of consanguineous families in developing countries [43]. More than 20 loci identified which may cause inherited autosomal non-syndromal hearing loss [44], with higher rate of incidence in consanguineous families [45]. Studies on UK Pakistanis show high rate of cerebral palsy cerebral palsy in consanguineous matrimony [46] with the autosomal recessive gene located on chromosome 2q [24- 25]. This gen has been identified in several consanguineous families with affected progenies [47]. The adult offspring of consanguineous families are more represented in institutions for caring mental retardation patients [48] but association between consanguineous marriage and adult-onset behavioral and psychiatric disorders (like schizophrenia) have not yet been clearly described [49- 51]. Although a preliminary report from Pakistan suggests that the prevalence of certain cancers and cardio-vascular disease are higher in consanguineous progenies [52].
Considering results of this study, it is highly recommended that consanguineous marriages be prevented especially if previous consanguinity is present in the family. For those couples who are first or second cousins, pedigree chart of their four generation should be provided (including offspring, siblings, parents, grandparents, aunts, uncles, nieces, nephews, and first cousins) and studied for any congenital anomalies or early death. Also, the presence of some disease like birth defects or congenital anomalies, early hearing impairment, early vision impairment, mental retardation or learning disability, developmental delay or failure to thrive, inherited blood disorder, unexplained neonatal or infant death in offspring, epilepsy and undiagnosed severe condition, should be queried. For families with known autosomal recessive disorders, clinical and molecular diagnosis should be established if possible. Predictive premarital genetic testing should be carried out on prospective consanguineous couples; if diagnosis fails then risk estimation should be taken into account. For consanguineous couples with affected children prenatal diagnosis can be done if possible.


Congenital anomalies in this family are: death within first month of birth mostly because of malformation of gastro-intestinal system while some were unrecognized, hearing deficit, mental retardation, cerebral palsy, and kyphosis. Several studies have also shown the existence of a relationship of above conditions and defects with consanguineous parents. Regarding kyphosis, however, there is no specific study to show its relationship to consanguinity.


  1. Teebi A. Genetic Diversity among the Arabs, Genetic Disorders among Arab Populations 2010. Springer. 

  2. Darr A, Model B. The Frequency of Consanguineous Marriage among British Pakistanis. J Medical Genetics 1988; 25: 186-190.

  3. Al-Gazali L, Hamamy H. Consanguinity Dysmorphology in Arabs. Hum Hered 2014; 77: 93-107.

  4. Fuster V, Colantonio SE. Socioeconomic, demographic, and geographic variables affecting the diverse degree of consanguineous marriage in Spain. Hum Bio 2004; 76: 1-14.

  5. Jaber L, Shohat M, Halpern GJ. Demographic characteristics of the Israeli Arab community in concentration with consanguinity. Isr J Med Sci 1996; 32: 1286-1289.

  6. Bener A, Hussain R, Teebi AS. Consanguineous marriages and their effects on common adult disease: studies from an endogamous population. Med Princ Pract 2007; 166: 262-267.

  7. Rosano A, Botto DL, Botting B, Mastroiacovo P. Infant mortality and congenital anomalies from 1950 to 1994: an international perspective. J Epidemiol Community Health 2000; 54: 660-666.

  8. Agha MM, Williams JI, Marrett L, To T, Dodds L. Determinants of survival in children with congenital abnormalities: a long- term population-based cohort study. Birth Defects Res A Clin Mol Teratol 2006; 76: 46-54.

  9. Kalter H, Warkany J. Congenital malformations: etiologic factors and their role in prevention (first two parts). The N Eng J Medn 1983; 308: 424-431.

  10. Temtamy SA, Meguid A, Mazen N, Ismail I, Kassem SR, et al. A genetic epidemiological study of malformations at birth in Egypt. East Mediterr Health J 1998; 4: 252-259.

  11. Biri A, Onan A, Korucuoglu U, Tirans B. Birth prevalence and distribution of congenital anomalies in a university hospital. Perinatal Dergisi 2005; 13: 86-90. 

  12. Imaizumi Y, Shinozaki N. Frequency of consanguineous marriages in Japan: geographical variations. Jpn J Hum Genet 1984; 29: 381-385.

  13. Mokhtar MM, Abdel-Fattah M. Major birth defects among infants with Down syndrome in Alexandria, Egypt (1995-2000): trends and risk factors. East Mediterr Health J 2001; 7: 441-451.

  14. Khoury SA, Massad D. Consanguineous marriage in Jordan. Am J Med Genet 1992; 43: 769-775.

  15. Sueyoshi S, Ohtsuka R. Effects of polygyny and consanguinity on high fertility in the rural Arab population in South Jordan. J Bio Soc Sci 2003; 35: 513-526.

  16. Rajangam S, Devi R. Consanguinity and chromosomal abnormality in mental retardation and or multiple congenital anomaly. J Anat Soc India 2007; 56: 30-33.

  17. Kupka K. International classification of disease: ninth revision. WHO chronical 1978; 32: 219-225.

  18. Pedersen J. The influence of consanguineous marriage on infant and child mortality among Palestinians in the West Bank and Gaza, Jordan, Lebanon and Syria. Community Genet 2002; 5: 178-181.

  19. Schull WJ. Empirical risks in consanguineous marriage: sex ratio, malformation and viability. Am J Hum Genet 1958; 10: 294-343.

  20. Ayesh SK, Suheir M, Nassar WA, Al-Sharef BY, Abu-Libdeh H.Genetic screening of familial Mediterranean fever mutations in the Palestinian population. Saudi Med J 2005; 26: 732-737.

  21. Gatrad AR, Read AP, Watson GH. Consanguinity and complex cardiac anomalies with situs ambiguous. Arch Dis Child 1984; 59: 242-245

  22. Tandon A, Sengupta S, Shukla V, Danda S. Risk Factors for Congenital Heart Disease (CHD) in Vellore, India. Current Res J Bio Sci 2010; 2: 253-258.

  23. Bener A, Abdulrazzaq YM, Al-Gazali L, Micallef I, Al-Khayat R, et al. Consanguinity and associated socio-demographic factors in the United Arab Emirates. Hum Hered 1996; 46: 256-264.

  24. Roberts JAF, Pembrey ME (eds.). Cousin Marriage. In: An Introduction to Medical Genetics Oxford University, New York 1978.

  25. Bittles AH. Consanguineous marriage and childhood health. Dev Med Child Neurol 2003; 45: 571-576.

  26. Rajech S, Athamny E, Khatib M, Sheikh-Muhammad A, Azem A, et al. Consanguinity and Its Effect on Morbidity and Congenital Disorders Among Arabs in Israel. Human Genetic Diseases 2011; 267-276.

  27. Devi ARR, Rao NA, Bittles AH. Inbreeding and the incidence of childhood genetic disorders in Karnataka, South India. J Med Genet 1987; 24: 362-365.

  28. Alwan A, Modell B. Recommendations for introducing genetics services in developing countries. Nat Rev Genet 2003; 4: 61-68.

  29. Puri RK, Verma IC, Bhargava I. Effects of consanguinity in a community in Pondicherry. In: Verma IC (eds.). Med Genet India, Pondicherry 1978.

  30. Hashmi MA. Frequency of consanguinity and its effect on congenital malformation-a hospital based study. J Pak Med Assoc 1997; 47: 75-78.

  31. Saify KH, Saadat M. Consanguineous Marriage in Afghanistan. J Biosoc Sci 2012; 44: 73-81.

  32. Wahab A, Ahmad M, Shah A. Migration as determinant of marriage pattern: preliminary report on consanguinity among Afghans. J Biosoc Sci 2006; 38: 315-325.

  33. Hussain R. Community perceptions of reasons for preference for consanguineous marriages in Pakistan. J Biosoc Sci 2000; 31: 449-461.

  34. Bittles AH, Neel JV. The costs of human inbreeding and their implications for variations at the DNA level. Nature Genet 1994; 8: 117-121.

  35. Jaber L, Merlob P, Gabriel R, Shohat M. Effects of consanguineous marriage on reproductive outcome in an Arab community in Israel. J Med Genet 1997; 34: 1000-1002.

  36. Bittles AH, Grant JC, Shami SA. An evaluation of consanguinity as a determinant of reproductive behavior and mortality in Pakistan. Intl J Epidem 1993; 22: 463-467.

  37. Grant JC, Bittles AH. The comparative role of consanguinity in infant and childhood mortality in Pakistan. Ann Hum Genet 1997; 61: 143-149.

  38. Cnattingius YM, Jalil S, Zaman F, Iselius S, Gustavson K. Risk factors for mortality in young children living under various socio-economic conditions in Lahore, Pakistan: with particular reference to inbreeding. Clin Genet 1998; 54: 426-434.

  39. Coskun OI, Tokol T, Demircin S, Monch E. Metabolic disorders in Turkey. J Inher Metab Dis 1990; 13: 732 -738.

  40. Bundey S, Alam H. A ve-year prospective study of the health of children in different ethnic groups, with particular reference to the effect of inbreeding. Eur J Hum Genet 1993; 1: 206-219.

  41. Hutchesson AC, Bundey S, Preece MA, Hall SK, Green A. A comparison of disease and gene frequencies of inborn errors of metabolism among different ethnic groups in the West Midlands. J Med Genet 1998; 35: 366- 370.

  42. Zlotogora J. Genetic disorders among Palestinian Arabs. Am J Med Genet 1997; 68: 472-475.

  43. Bittles AH. Reproductive behavior and health in consanguineous marriages. Science 1991; 252: 789- 794.

  44. Willems PJ. Genetic causes of hearing loss. N Engl J Med 2000; 342: 1101-1109.

  45. Sundstrom RA, Laer LV, Camp GV, Smith RJH. Autosomal recessive nonsyndromic hearing loss. Am J Med Genet 1999; 89: 123-129.

  46. Corry SG, Subesinghe P, Wild DJ, Levene MI.  Prevalence and type of cerebral palsy in a British ethnic community: the role of consanguinity. Dev Med Child Neurol 1997; 39: 259-262.

  47. McHale DP, Mitchell S, Bundey S, Moynihan L, Campbell DA, Woods CG, Lench NJ, Mueller RF, Markham AF. A gene for autosomal recessive symmetrical spastic cerebral palsy maps to chromosome 2q24-25. Am J Hum Genet 1999; 64: 526-532.

  48. Farag TI, Al-Awadi SA, El-Badramary MH, Aref MA, Kasrawi B, Krishna Murthy DS. Disease proile of 400 institutionalized mentally retarded patients in Kuwait. Clin Genet 1993; 44: 329-334.

  49. Ahmed AH. Consanguinity and schizophrenia in Sudan. Br J Psychiat 1979; 134: 65-636.

  50. Ødegard SL. Inbreeding and schizophrenia. Clin Genet 1986; 30: 261–275.

  51. Chaleby K, Tuma TA. Cousin Marriages and schizophrenia in Saudi Arabia. Br J Psychiat 1987; 150: 547- 549.

  52. Shami SA, Qaisar R, Bittles AH. Consanguinity and adult morbidity in Pakistan (letter). Lancet 1991; 338: 954-955.