Introduction
A consanguineous marriage is usually defined as a marriage between people who are second cousins or closer (Bittles, Reference Bittles1994). It is estimated that globally at least 20% of the human population live in communities with a preference for consanguineous marriage, and that at least 8.5% of children have consanguineous parents (Bittles, Reference Bittles1990).
Consanguinity is common in several populations of the world. However, consanguinity rates vary from country to country. Furthermore, there is variability between different tribes, communities and ethnic groups within the same country (Bittles, Reference Bittles1990). This difference is usually related to race, the isolation of the society and religion.
To date, there is little information on consanguinity in Morocco. The prevalence of consanguinity in Morocco reported to date varies in the range of 19.81–28.00% (Bouazzaoui, Reference Bouazzaoui1994; Hami et al., Reference Hami, Soulaymani and Mokhtari2006; Cherkaoui et al., Reference Cherkaoui, Baali, Larrouy, Sevin and Boëtsch2005; Talbi et al., Reference Talbi, Khadmaoui, Soulaymani and Chafik2007). These studies were mainly limited to one region of Morocco and reflect only the activity of a specific medical centre.
Consanguineous mating is genetically an important phenomenon as it brings about an increase in homozygous genotypes and a decrease in the corresponding heterozygous form (Thompson et al., Reference Thompson, McInnes and Willard1991). The association between consanguineous marriages and genetic defects has been observed for a long time. The diseases observed in the offspring of these marriages include those resulting from autosomal recessive inheritance.
Consanguinity continues to attract attention among medical and population geneticists, clinicians and social scientists. The decline in infant mortality rates in Morocco through the improvement in childhood nutritional status and combating infectious disease means that genetic disorders will assume an ever-increasing importance. For this reason, it was felt that it was important to study the rate of consanguineous marriages associated with autosomal recessive disorders, to estimate the average inbreeding coefficient in the Moroccan population and to verify the true risks for offspring of consanguineous parents in a population that favours consanguinity and condemns it as the cause of autosomal recessive disorders.
The information presented in this study defines better the health risks associated with consanguinity and provides genetic data to support educational guidelines targeted at the public and the health sector.
Methods
The study was carried out in the Department of Medical Genetics of the National Institute of Health in Rabat, Morocco. Consanguinity rates were studied for 176 families with autosomal recessive disorders that were diagnosed and confirmed by molecular analysis in the department: deafness, familial Mediterranean fever, spinal muscular amyotrophy, autosomal recessive muscular dystrophy, beta-thalassaemia, and other rare autosomal recessive diseases confirmed by clinical, radiological, enzymatic or molecular investigations.
To study the rate of consanguinity in the general population, 852 families were included in this study; they all had infants with trisomy 21 (Down syndrome) confirmed by karyotyping. These families were chosen because there is no association between trisomy 21 and consanguinity, and these cases are referred from different regions of Morocco to public and private hospitals. In addition, these families come from all social backgrounds and in addition, trisomy 21 is the most common clinical reason for performing cytogenetic investigations. The genealogical data were obtained from the files of patients. The degree of consanguinity between each female and her spouse, and the degree of consanguinity between their parents were recorded.
Consanguineous marriages were classified into first cousins (includes parallel paternal, parallel maternal, cross and double first cousins) and beyond first cousins (including first cousins once removed and second cousins); other couples were related with a distant consanguinity, and those reported as from the same tribe were considered non-consanguineous.
Moreover, the consanguinity profile was compared for the general population with the consanguinity profile of families with autosomal recessive diseases.
Results
The rate of consanguinity was evaluated in 176 couples with children with autosomal recessive disorders that were diagnosed and confirmed by molecular analysis in the department: deafness, familial Mediterranean fever, spinal muscular amyotrophy, autosomal recessive muscular dystrophy, beta-thalassaemia, and other rare autosomal recessive diseases confirmed by clinical, radiological, enzymatic or molecular investigations (Leber's congenital amaurosis, Xeroderma pigmentosum, Mucopolysaccharidosis type 3, Pycnodysostosis, Phenylketonuria, Omenn syndrome and miscellaneous).
Consanguineous marriages comprised 59.09% of all marriages in families with autosomal recessive diseases, including the rare autosomal recessive disorders. Moreover, these rare diseases were diagnosed in 22 families. In six families with Leber's congenital amaurosis, four families with Xeroderma pigmentosum, four families with Phenylketonuria, two families with Sanfilippo syndrome, two families with Pycnodysostosis and one family with Omenn syndrome (Jaouad et al., Reference Jaouad, Ouldim, Ali Ou Alla, Kriouile, Villa and Sefiani2008), the parents were first cousins. The consanguinity rate in these families with rare autosomal recessive diseases was found to be 86.36%. The difference in rates of consanguineous marriages was highly significant when comparing the general population with couples with offspring affected by autosomal recessive conditions.
Of the 852 families presenting with a child with trisomy 21, 130 were found to be consanguineous, giving an overall rate of consanguinity of 15.25% with a coefficient of inbreeding of 0.0065 (Table 1).
Table 1. Consanguinity profile in the Moroccan population for this study and other Moroccan studies
a First cousins once removed are not included in this prevalence.
All types of consanguineous marriages were high, but the most common type of consanguineous marriage was between first cousins, constituting 58.46% of the total consanguineous marriages and 8.92% of all marriages. First cousins once removed and second cousin marriages were common (4.34% of all marriages).
Discussion
Morocco is one of the Mediterranean countries where consanguineous marriages are culturally favoured. It is an integral part of the cultural and social life of the country. The practice is frequent in all Moroccan populations, which are grouped according to cultural or linguistic differences; it is the result of a mixing of Arabs who speak Arabic and non-Arabs (northern–central Berbers who speak Tarifit and southern Moroccan Berbers who speak Tamazigh). This partition is not associated with genetic differentiation (Bosch et al., Reference Bosch, Calafell, Pérez-Lezaun, Clarimón, Comas and Mateu2000).
This study shows that autosomal recessive disorders are strongly associated with consanguineous marriages; the consanguinity rate among families with these diseases was found to be significantly different from the consanguinity rate among the general population. The effect is particularly marked for rare disorders, because a carrier is unlikely to find a partner who carries the same disorder unless they are related. Therefore, in communities in which consanguineous marriages are common, there is an increased risk prevalence of many rare autosomal recessive disorders. The study found an increase in consanguineous marriages among parents of patients affected by some rare autosomal recessive diseases.
Sometimes autosomal recessive genes are hidden within the family for generations and they only come to the surface in a new consanguineous marriage within the family. In Morocco, more and more consanguineous couples are seeking premarital counselling. They are interested in knowing the risks that their future offspring carry in developing a genetic or congenital disorder, together with associated physical or mental retardation. In a society where selective termination of an affected fetus is restricted, it is important to introduce measures for prevention and control of genetic diseases by developing prospective genetic counselling for families with recessive gene disorders and by performing premarital testing and screening whenever feasible.
Autosomal recessive diseases and consanguinity have also a scientific interest in the localization and the identification of genes. Baala et al. Reference Baala, Briault, Etchevers, Laumonnier, Natiq and Amiel(2007) reported an autosomal recessive microcephaly syndrome in a consanguineous Moroccan family, cosegregating with a homozygous balanced translocation between chromosomes 3p and 10q that has a position effect at the breakpoint on chromosome 3, which silences the eomesodermin transcript.
The present study also reports the prevalence of consanguinity in Morocco and places Morocco among the countries in the world with quite a high rate of consanguinity. However, this rate is lower when comparing it with those of other countries such as Algeria (Benallegue & Kedji, Reference Benallegue and Kedji1984), Egypt (Hafez et al., Reference Hafez, El-Tahan, Awadalla, El-Khayat, Abdel-Gafar and Ghoneim1983), Lebanon (Khlat, Reference Khlat1988), Tunisia (Riou, Reference Riou, el Younsi and Chaabouni1989) and Saudi Arabia (Al Husain & Al Bunyan, Reference Al Husain and Al Bunyan1997). The consanguinity rates in Morocco and other Arab countries are significantly higher than in South and North American, European, South African, Eastern Asian and Oceanic countries (Bittles, Reference Bittles1990).
The inbreeding coefficient (F) also places Morocco among the countries in the world with quite a high rate of inbreeding. In Western countries, where consanguineous mating occurs at a low frequency, the inbreeding coefficient is low, for example in Canada (F=0.00004–0.0007), in the United States (F=0–0.0008) and in southern Europe (F=0.001–0.002). However, in populations with higher consanguinity rates, the values are higher: for example, in Saudi Arabia (F=0.024) and in Egypt (F=0.01).
There are several underlying factors that may operate to encourage consanguineous marriages. In Morocco, the high rate of consanguinity may be attributed to social and traditional factors and to the desire to keep property within families. The main factors that inspire consanguinity include social and economic benefits. Marriage between relatives is considered beneficial as it maintains the family fortunes within the same family structure.
The reasons that people give for preferring consanguineous marriage include: strengthening of family ties; relative ease for both men and women in finding a suitable partner; support for the woman's status, as well as better relationships with her in-laws (Bittles et al., Reference Bittles, Mason, Greene and Rao1991; Hussain, Reference Hussain1999); and care for people in old age. Also, consanguineous marriages are more stable than marriages between unrelated partners; the male and female grow up in the same or similar environment of the family and therefore adjust more easily after the marriage.
However, the rate of consanguinity seems to be decreasing in frequency among the younger generation. The changes observed over time may be attributable to several factors including: (i) the decrease in the number of offspring per family, which reduces significantly the possibility of consanguinity since a smaller number of cousins are available for marriage, (ii) the increase in the level of education of women, (iii) the adoption of the nuclear family system, (iv) the displacement from rural to urban areas, (v) an improved socioeconomic status for families, (vi) an increase in the proportion of women in the work force, (vii) and an increased recognition of the effects of consanguineous marriages on child health in families where there is a case(s) of an inherited recessive disease.
Several studies have described aspects of morbidity, mortality and genetic effects of consanguineous mating. Recessive disorders are the only conditions that are clearly more common when parents are related. Excess mortality is directly related to the degree of inbreeding (Benallegue & Kedji, Reference Benallegue and Kedji1984; Schulpen et al., Reference Schulpen, Van Wieringen, Van Brummen, van Riel, Beemer, Westers and Huber2006).
In conclusion, consanguineous marriage is an integral part of the cultural and social life of Morocco, and attempts to discourage it at the population level appear to be inappropriate and undesirable (Alwan & Modell, Reference Alwan and Modell1997). Nevertheless, the approaches recommended by the WHO to minimize the negative effects of consanguinity on child health should be followed; for example, the identification of families with a high risk of a genetic disease and the provision of prospective genetic counselling.
Families with segregating autosomal recessive conditions are usually advised to limit further intermarriages among high at-risk carriers in the family if carrier testing is not available.
It is essential to include education of the public and health personnel in programmes for the prevention and control of genetic and congenital disorders. These educational programmes should define the health risks associated with consanguinity.
Acknowledgment
The authors extend their sincere thanks to all the staff of the Department of Medical Genetics of the National Institute of Health for their continuous support. They thank Dr M. C. Brahimi-Horn of the Department of Medical Genetics in Rabat, Morocco, and of Inserm, France, for editorial assistance. This work was done within the framework of the Laboratoire International Associé (LIA).
