genetic disorders among arab populations || endogamy and consanguineous marriage in arab populations

Chapter 4

Endogamy and Consanguineous Marriage

in Arab Populations

Alan H. Bittles and Hanan A. Hamamy

Introduction

Arabs are a Semitic people basically defined as individuals speaking Arabic as their

native tongue, although with many different dialects, who self-identify as being of

Arab ancestry. The Arab world extends from Iraq and the Gulf States in the east to

Morocco and Mauritania on the Atlantic coast of North Africa in the west, and

through time it has incorporated many populations with ancestral origins outside

the Arabian Peninsula. Large Arab communities are now permanent residents in

Western Europe, North and South America, and Australia, and so the global Arab

population is estimated to number 300–350 million (Hamamy and Bittles 2009).

All Arabs share certain core cultural values and beliefs, with the family accepted

as the central structure of society. Marriage is primarily regarded as a family matter

and arranged marriage is widespread within all Arab societies. The practice of

arranged marriage does not entail a union contracted against the will of the partners

but essentially reflects the fact that the marriage has been mutually agreed by both

families on familial and traditional grounds.

Traditional and Contemporary Patterns of Endogamy

in Arab Societies

Although social life and identity traditionally focuses on the family, family ties

extend into the structure of clans and tribes, and for this reason an individual’s sense

of loyalty continues to be oriented to extended patrilineal kin relations, i.e., the

hamula or clan, and more widely to the tribe. Family support is expected in all

A.H. Bittles (*)

Centre for Comparative Genomics, Murdoch University, South Street, Perth, WA 6150, Australia

e-mail: [email protected]

A.S. Teebi (ed.), Genetic Disorders Among Arab Populations,DOI 10.1007/978-3-642-05080-0_4, # Springer-Verlag Berlin Heidelberg 2010

85

circumstances, and so “one turns to a member of the family for assistance in almost

any area, whether it is a question of health, financial need, employment, or even

admission to school” (Khlat 1997).

Tribal structure and composition can change through time and for example, a

detailed study of the Abbad tribe in Jordan indicated that the present-day grouping

coalesced approximately 250 years ago from a number of quite diverse sub-groups,

which had previously been affiliated with other older tribal communities (Nabulsi

1995). The Abbad tribe now incorporates some 120,000 individuals and is sub-

divided into 76 male lineages, ranging in numbers from approximately 250 to 2,000

persons. Some 90% of marriages are contracted within the tribe, and half of all

marriages are between members of the same paternal descent line (Nabulsi 1995).

Given this complex tribal and clan structure and the quite restricted effective

population sizes of many sub-groups, a substantial level of random inbreeding is

inevitable within Arab communities and internal genetic differentiation is probable

on the basis of tribe and clan membership. However, the degree to which these

processes apply will be dependent on the specific history of each tribe and clan, and

more particularly on past and present frequencies and patterns of tribal admixture

and inter-clan marriage.

Marriage within tribal boundaries is largely paralleled by religious endogamy.

In multi-faith countries such as Lebanon, with three main religious communities,

Sunni and Shia Muslims and Maronite Christians, plus the smaller Druze, Greek

Orthodox, Greek Catholic and Armenian communities, denominational endogamy

has historically been the norm and is accompanied by a variable level of genetic

differentiation (Klat and Khudr 1986).

Consanguineous Marriage Within Arab Societies

As previously noted, Arab societies place great emphasis on the role and impor-

tance of the family. Thus, in addition to tribal and clan endogamy, consanguineous

marriage is customary in most, if not all, Arab communities.

The Prevalence and Preferred Types of Consanguineous Marriage

Intra-familial unions between couples related as second cousins or closer

(F � 0.0156) currently account for approximately 20–50% of all marriages in

Arab countries (Table 4.1). Specific inter-country comparisons are often difficult

because of the different study populations sampled, for example, through household

surveys versus antenatal clinics or maternity wards, and researchers also vary in the

level of detail collected, with some studies based on data on first-cousin and non-

consanguineous marriages only.

86 A.H. Bittles and H.A. Hamamy

Table

4.1

Prevalence

andtypes

ofconsanguineousmarriagein

representativestudiesonArabpopulations

Country

Studyregion

Consanguinity(%

)Marriages

studied

Meancoefficient

ofinbreeding(a)

Reference

Algeria

All-A

lgeria

22.6

1C,2C

–BenallegueandKedji(1984)

Bahrain

Bahrain

31.8

1C,11/2C,2C

0.0152

AlArrayed

(1994)

Egypt

All-Egypt

24.5

D1C,1C,11/2C,2C

0.0101

Hafez

etal.(1983)

Iraq

All-Iraq

33.0

D1C,1C

0.0219

COSIT

(2005)

Israel

ArabMuslim

32.1

D1C,1C,11/2C,2C

0.0177

Vardi-Saliternik

etal.(2002)

Jordan

Amman

25.5

D1C,1C,11/2C,2C

0.0142

Ham

amyet

al.(2005)

Kuwait

All-K

uwait

34.3

D1C,1C,11/2C,2C

0.0219

Al-Awadiet

al.(1985)

Lebanon

Beirut

25.0

1C,<

1C

0.0088

Khlat(1988)

Morocco

All-M

orocco

19.9

1C,2C

0.0089

Lam

douar

Bouazzaoui(1994)

Oman

All-O

man

35.9

D1C,1C,11/2C,2C

0.0198

Rajab

andPatton(2000)

PalestinianTerritories

All-Palestine

27.7

D1C,1C

0.0186

Assaf

andKhaw

aja(2009)

Qatar

Doha

44.5

D1C,1C,11/2C,2C

0.0271

Bener

andAlali(2006)

SaudiArabia

All-Saudi

40.6

1C,2C

0.0184

El-Hazmiet

al.(1995)

Sudan

Khartoum

52.0

1C,2C

0.0302

SahaandElSheikh(1988)

Tunisia

Northregion

26.9

>1C,1C,11/2C,2C

0.0181

Riouet

al.(1989)

United

ArabEmirates

AlAin

37.4

D1C,1C,11/2C,2C

0.0245

Al-Gazaliet

al.(1997)

Yem

enSana’a

44.7

D1C,1C,11/2C,2C

0.0244

Gunaidet

al.(2004)

Marriages

studied:

D1Cdouble

firstcousin,F¼

0.125

1Cfirstcousin,F¼

0.0625

11/2Cfirstcousinonce

removed,F¼

0.0313

2Csecondcousin,F¼

0.0156

Sou

rce:

www.consang.net

4 Endogamy and Consanguineous Marriage in Arab Populations 87

http://www.consang.net

It is important to acknowledge that the consanguinity estimates and mean

coefficients of inbreeding reproduced in Table 4.1 refer only to relationships that

extend back to the grandparental generation. Given the long history and preference

for consanguineous marriage in Arab societies and their tradition of tribe and clan

endogamy, the cumulative levels of inbreeding and thus the percentage of homo-

zygosity would be substantially higher than suggested by these data.

Determination of ancestry in Arab societies and the construction of family

pedigrees are greatly advantaged by the precise terminology that exists in Arabic

to describe various family relationships. First-cousin unions are especially popular,

in particular the paternal parallel subtype ‘Bint amm, i.e., between a man and his

father’s brother’s daughter. ‘Bint amm unions are favoured culturally and socially

and they are considered to be the usual or expected form of marriage for first

cousins whether they have been reared in adjoining or separate households.

As indicated in Table 4.2, parallel-cousin marriages (‘Bint amm and ‘Bint khala)predominate in Arab countries, ranging from 59.9% of first-cousin unions in

Lebanon (Khlat 1985) to 73.3% in UAE (Al-Gazali et al. 1997). The prevalence

of ‘Bint amm marriages varies significantly between populations, with the lowest

rates in urban Lebanon (Khlat 1985) and the highest in lower income, rural and

Bedouin tribal communities (Khlat et al. 1986; Radovanovic et al. 1999; Raz and

Atar 2004; Joseph 2007). However, no hard and fast rule exists, and in communities

or extended families with few marriageable offspring, it may be difficult to ensure

that a ‘Bint amm, or indeed any other type of first-cousin marriage, is possible

within the socially acceptable age differences of the groom and bride.

In more traditional Arab societies it is held that a man has the common-law right

(urf) to marry his first cousin, and if she marries another male he may be entitled to

Table 4.2 Preferred patterns of first cousin marriage in different Arab societies

Country Type I

(%)

Type II

(%)

Type III

(%)

Type IV

(%)

All first

cousin

Authors

‘Bint amm ‘Bint khala ‘Bint amma ‘Bint khal unions (%)

Lebanon 37.4 22.5 10.4 29.7 14.1 Khlat (1985)

Jordan 62.8 9.9 7.7 11.3 32.0 Khoury and

Massad (1992)

UAE 64.9 8.4 12.2 14.5 26.2 Al-Gazali et al.

(1997)

Israel 48.2 20.3 13.5 17.7 24.3 Jaber et al. (2000)

Yemen 48.9 18.1 14.2 18.8 29.4 Gunaid et al.

(2004)

Palestinian

territories

47.9 17.6 20.1 14.4 14.4 Assaf and

Khawaja

(2009)

Parallel-cousin marriage

Type I father’s brother’s daughter, F ¼ 0.0625, Fx ¼ 0

Type II mother’s sister’s daughter, F ¼ 0.0625, Fx ¼ 0.1875

Cross-cousin marriage

Type III father’s sister’s daughter, F ¼ 0.0625, Fx ¼ 0

Type IV mother’s brother’s daughter, F ¼ 0.0625, Fx ¼ 0.125


financial compensation (El-Badramany et al. 1997; Joseph 2007). In practice, the

girl’s paternal uncle can agree to forego his son’s right to their marriage (Joseph

2007). If his permission is not granted, practices such as revoking the marriage of a

cousin to another man have persisted in some Palestinian villages, even occurring

on the marriage night (Assaf and Khawaja 2009).

While all four types of first-cousin marriage have the same coefficient of

inbreeding at autosomal loci (F ¼ 0.0625), an often understated factor is the differ-

ence in the equivalent coefficient of inbreeding at X-chromosome loci (Fx). Asshown in Table 4.2, from a theoretical perspective, homozygosity at X-chromosome

loci is zero for ‘Bint amm and ‘Bint amma progeny, but Fx ¼ 0.125 for ‘Bint khaland 0.1875 for ‘Bint khala offspring. As a result, it would be expected that the

expression of X-chromosome disorders, such as glucose 6-phosphate dehydroge-

nase deficiency, reflects the proportional prevalence of each first-cousin sub-type in

a population.

Religion and Consanguinity

It is generally accepted that consanguineous marriage in the Arab world is a pre-

Islamic tradition (Stern 1939). The practice may, however, have been encouraged

by the rules of inheritance introduced by the Holy Quran, with daughters entitled to

inherit half of the amount received by sons and the wife inheriting a determinate

share from her husband (Sura Al-Nisa: 7,11,12). Under Islamic law, a dower (mahr)is specified as part of the marriage arrangement, with these goods transferred to the

bride at marriage (Khuri 1970; Tucker 1988).

Consanguineous marriage is also common within Christian Arab communities,

although usually at a lower prevalence than among their Muslim compatriots

(Freundlich and Hino 1984; Khlat 1988). In Arab Christian denominations affiliated

with the Roman Catholic Church, and in the Greek Orthodox Church, religious

dispensation requirements may apply to marriages contracted between couples

related as first cousins or closer, whereas in the Coptic Orthodox Church no such

regulation applies to first-cousin unions.

The basic guidelines on permitted marital relationships within Islam allow

marriages up to and including first-cousin unions (F ¼ 0.0625) to be contracted.

Uncle–niece marriage (F ¼ 0.125) is proscribed by the Holy Quran. However,

double first-cousin marriage, also F ¼ 0.125, is allowed within Islam and the

current prevalence of double first-cousin unions typically ranges from 0.6% to

5.8% (Al-Gazali et al. 1997; Radovanovic et al. 1999).

It has been mistakenly assumed that consanguineous marriage is favoured within

Islam, when a number of the hadith (oral pronouncements of the Prophet Muhammad)

actually encourages marriage between non-relatives (Hussain 1999). In addition,

the second Caliph, Omer Ibn Al-Khatab, reputedly advised the Bani Assayib tribe

to avoid close-cousin marriage and resultant ill-health by intermarrying with other

tribes (Albar 1999). Nonetheless, Fatima, the daughter of the Prophet, married Ali,


the Prophet’s ward and first cousin, so in practice the advice offered on consan-

guinity appears not to have been intended or regarded as binding.

Demographic, Social and Economic Correlates of Consanguinity

Across the Arab world, consanguineous marriage is most prevalent in rural com-

munities following more traditional life styles (Al-Salem and Rawashdeh 1993;

Al-Gazali et al. 1997; Radovanovic et al. 1999; Zaoui and Biemont 2002;

El-Mouzan et al. 2007; Joseph 2007). In general, the highest prevalence of consan-

guineous marriage is contracted among families with the lowest standard of living

(Saedi-Wong et al. 1989; Assaf and Khawaja 2009) and wives in consanguineous

marriages mostly have a lower level of education (Al-Thakeb 1985; Khlat 1988;

Jurdi and Saxena 2003). As indicated in Table 4.3, in keeping with a more

traditional lifestyle, consanguinity is generally associated with younger maternal

and paternal ages at marriage and so longer female reproductive spans (Khlat 1988;

Assaf and Khawaja 2009).

These generalisations are by no means uniform, and historical records from

eighteenth and nineteenth century Palestine indicate that cousin marriage was most

prevalent in upper-class Arab societies (Tucker 1988). Upper socioeconomic status

males in Kuwait favour consanguineous marriage (Al-Thakeb 1985), and males

with advanced educational backgrounds express a similar preference for intra-

familial marriage in the UAE (Bener et al. 1996) and Yemen (Jurdi and Saxena

2003). Representative surveys in the Palestinian Territories also showed no signifi-

cant difference in the prevalence of consanguineous marriage across female educa-

tional standards (Assaf and Khawaja 2009).

A small number of detailed studies have been conducted into the social out-

comes of consanguineous marriage, although they have mainly involved female

subjects only. An early report from Sudan indicated greater marital stability in

consanguineous unions, irrespective of the type of cousin relationship, with divorce

in 3.6% of first-cousin marriages as against 14.6% in other types of marriage

(Hussien 1971). This pattern has also been reported in non-Arab populations,

possibly because of the highly disruptive effect of marriage failure on the stability

of the extended family (Bittles 2005).

Table 4.3 Demographic and social correlates

of consanguinity

Younger maternal and paternal age at marriage

Extended maternal reproductive span

Larger completed family sizes

Low level of maternal education

Rural residence

More traditional mode of life


A higher degree of dissatisfaction may, however, arise when there is a large age

differential between consanguineous partners (El-Islam 1976), and in Saudi Arabia

there was a positive but statistically non-significant association between the degree

of consanguinity and marital discord (Chaleby 1988). More recent investigations

have centred on the highly sensitive issue of domestic violence, with no significant

advantage or disadvantage reported for consanguineous marriage among low-

income women in Syria (Maziak and Asfar 2003) or Palestinian refugees in

Lebanon (Khawaja and Tewtel-Salem 2004).

Contemporary Attitudes Toward Consanguineous Marriage

As shown in Table 4.4, when questioned about consanguineous marriages, a

number of reasons are commonly advanced for the popularity of intra-familial

unions (Hamamy and Bittles 2009). In general, besides various social and economic

explanations, women who married a close biological relative or whose family has a

tradition of consanguineous unions are more favourably disposed to the practice

(Khlat et al. 1986; Jaber et al. 1996). The fact that espoused partners would have

met at family gatherings before betrothal is held to be especially helpful, and it

is also useful in promoting and achieving harmony between a bride and her future

in-laws to whom she is related (Khlat et al. 1986).

Some studies have reported a secular decline in the prevalence of consanguine-

ous marriages, for example, in Beirut, Lebanon (Khlat 1985), urban Kuwait

(Radovanovic et al. 1999), Saudi Arabia (Al-Abdulkareem and Ballal 1998), Jordan

(Hamamy et al. 2005), Israeli Arab communities (Jaber et al. 2000; Zlotogora et al.

2002; Sharkia et al. 2007) and the Palestinian Territories (Assaf and Khawaja

2009). By comparison, in the UAE (Al-Gazali et al. 1997), Yemen (Jurdi and

Saxena 2003) and Qatar (Bener and Alali 2006), the overall levels of consanguine-

ous marriage and the prevalence of first-cousin unions have actually increased. The

latter observations may reflect the larger family sizes of recent generations and

hence the greater availability of potential cousin spouses. But some caution needs to

be exercised in interpreting and comparing the prevalence of consanguineous

marriages across time, especially given the different study populations sampled,

Table 4.4 Perceived social and economic advantages of consanguineous marriage

The assurance of marrying within the family and the strengthening of family ties

Simplified premarital negotiations, usually conducted in the partners’ early or late teens

Knowledge of one’s spouse prior to marriage

Greater social compatibility of the bride with her husband’s family, in particular her mother-in-law

Lower risk of undeclared health problems in the intended spouse

Reduced requirement for dowry payments, with consequent maintenance of the family goods

and monies

In land-owning families, maintenance of the integrity of family land-holdings


the variant study protocols employed, and the major economic and educational

changes which have occurred in most Arab countries during the second half of the

twentieth century (Bittles 2008).

Endogamy, Consanguinity and Genetic Disease

in Arab Populations

Of the six World Health Organization (WHO) Regions, the highest rate of severe

congenital disorders and genetic diseases that are lethal or could potentially cause

lifelong impairment was reported in the Eastern Mediterranean Region, with >65

affected children per 1,000 live births as opposed to 52/1,000 live births in Europe,

North America and Australia (Alwan and Modell 2003; Christianson et al. 2006).

The elevated level of inherited disorders in the Eastern Mediterranean Region can

mostly be attributed to higher rates of inherited blood disorders and other autosomal

recessive conditions, for example, with carrier rates of 2–15% for b-thalassaemia,

2–50% for a-thalassaemia, and 0.3–30% for sickle cell disease in Arab countries.

In addition, G6PD deficiency has been estimated to range from 2.5% to 27% in

different Arab countries (Hamamy and Alwan 1994; Alwan and Modell 1997;

Al-Gazali et al. 2006), possibly reflecting the elevated levels of homozygosity at

X-chromosome loci (Table 4.2).

The large sizes of many Arab families, in conjunction with clan/tribe endogamy

and high consanguinity rates, facilitate the expression of autosomal recessive

disorders, with rare or previously unreported syndromes and metabolic defects

especially apparent (Teebi 1994; Al-Gazali et al. 2005; Hamamy et al. 2007a, b).

Consanguineous marriages continue to be contracted within the Arab diaspora

in Western countries, and so the reported rates of inherited disease in these com-

munities are comparable to those in their countries of origin, including a large

proportion of autosomal recessive diseases and developmental disorders (Hoodfar

and Teebi 1996; Nelson et al. 1997).

Consanguinity and Reproductive Health

Increased numbers of pregnancies have been recorded in a majority of global

studies of consanguineous marriages and, in a meta-analysis of 30 populations,

on average first cousins had 11.9% more live-born children than non-consanguineous

couples (Bittles et al. 2002a). This pattern of higher fertility holds true in most Arab

populations (Khlat 1988; al-Abdulkareem and Ballal 1998; Hammami et al. 2005;

Kerkeni et al. 2007). The primary reasons are more probably social than biological,

with younger parental ages at marriage in consanguineous unions and longer

potential reproductive spans as important contributory factors (Table 4.3). In the

more traditional rural Arab communities where consanguineous marriage is most

prevalent, there may be a lower uptake of contraception with consequent larger

family sizes.


Most studies worldwide have shown that consanguinity is not associated with

increased abortion or miscarriage rates (Bittles et al. 2002a). With some exceptions

(Mokhtar and Abdel-Fattah 2001; Assaf et al. 2009), there was also no significant

association between consanguinity and prenatal losses in a majority of Arab

populations (Al-Awadi et al. 1986; Khlat 1988; Saha et al. 1990; Abdulrazzaq

et al. 1997; al Husain and al Bunyan 1997; Jaber et al. 1997a; al-Abdulkareem and

Ballal 1998; Khoury and Massad 2000; Saad and Jauniaux 2002; Kerkeni et al.

2007), but it has to be acknowledged that data on very early pregnancy terminations

are at best partial, and so an unknown proportion of these early losses may be

unrecorded.

Although information on stillbirths is more reliable, the reported outcomes with

respect to consanguinity are varied, with some studies reporting a positive associa-

tion (Khoury and Massad 2000; Mokhtar and Abdel-Fattah 2001; Assaf et al. 2009)

but no significant difference in stillbirth prevalence in consanguineous pregnancies

in a majority of cases (Al-Awadi et al. 1986; Khlat 1988; Saha et al. 1990;

Abdulrazzaq et al. 1997; al Husain and al Bunyan 1997; Jaber et al. 1997a; Kerkeni

et al. 2007). A cross-sectional study which reported an association between con-

sanguinity and apnoea of prematurity in Lebanon awaits confirmation in other

populations (Tamim et al. 2003).

Anthropometric Studies at Birth and in Childhood

Investigations into the influence of consanguinity on birth measurements, including

weight, recumbent length and head circumference, often produce conflicting

results. Thus in different Arab populations, a positive association between consan-

guinity and low birth weight was both reported (Al-Eissa et al. 1991; Jaber et al.

1997a; Mumtaz et al. 2007) and refuted (Khlat 1989; Saedi-Wong and al-Frayh

1989; Wong and Anokute 1990; al-Abdulkareem and Ballal 1998).

Possible reasons for these contradictory findings include the variability of the

investigative protocols employed, with a common lack of discrimination between

different levels of consanguinity, and limited or no control for potential confound-

ing factors, including socioeconomic status, and maternal nutrition, health status

and disease. The importance of these factors was demonstrated in a study in Jordan,

in which univariate analysis initially indicated a highly significant positive associa-

tion between consanguinity and low birth weight. However, this relationship dis-

appeared in multivariate analysis when control for age, body mass index, occupation,

education, smoking, gravidity, parity, medical problems during pregnancy and a

family history of premature deliveries was introduced (Obeidat et al. 2008).

Inbreeding depression in stature among school children was observed in Egypt

(Abolfotouh et al. 1990). But, as with birth weight, studies with better control

for the effect of socioeconomic variables on stature are needed, taking into consider-

ation the rapidly changing socioeconomic and nutritional parameters which have

occurred in most Arab countries.


Early Postnatal Mortality

In keeping with studies conducted in other major populations (Bittles 2001),

almost all data from Arab countries indicate higher postnatal mortality in con-

sanguineous versus non-consanguineous couples, especially during the first year

of life (Jaber et al. 1997a). For example, among Palestinian families resident

in different Middle Eastern countries, infant mortality among first cousin prog-

eny was on average 15/1,000 live births higher than in non-consanguineous

offspring (Pedersen 2002). Given the higher homozygosity that would be

expected in the progeny of biologically related couples, the findings are strongly

suggestive of deleterious recessive gene expression, although in most published

reports on Arab populations no specific causes of death were diagnosed to

support this contention.

Besides a larger number of pregnancies and live births and despite a higher

percentage of infant and childhood deaths, consanguineous couples commonly

have more surviving children. In some cases, these findings can be explained in

terms of differentials between consanguineous and non-consanguineous couples

with respect to factors such as socioeconomic status, religious affiliation and mar-

riage duration (Khlat 1988). Reproductive compensation is a probable additional

factor, with families replacing children who have died in infancy or early child-

hood, either through choice or via cessation of lactational amenorrhoea.

Consanguinity and Childhood Morbidity

Studies of childhood deafness (Zakzouk et al. 1993; Al-Gazali 1998; Attias et al.

2006; Khabori and Patton 2008), blindness (Al-Idrissi et al. 1992; Elder and

De Cock 1993) and dental anomalies, especially structural defects and malocclu-

sion (Maatouk et al. 1995), all have implicated parental consanguinity in the disease

aetiology. The case for a significant recessive gene contribution to deafness is

strongest, with 92% and 57% respectively of non-syndromic and syndromic deafness

examined in the UAE attributed to autosomal recessive inheritance (Al-Gazali 1998).

As in other major populations, a significantly elevated risk of birth defects has

been widely recorded in the progeny of Arab first-cousin couples. The actual rates

and types of congenital defect reported vary widely between populations, with

differing study protocols, highly variable sample sizes and limited control for

sociodemographic variables making a detailed summary and overall assessment

very difficult. In many instances, attempts to determine the genetic weighting are

also hampered by affected individuals being designated only as “consanguineous”,

which in Arab populations could range from F ¼ 0.0156 to 0.125, or “non-

consanguineous” (F ¼ 0).

Percentage consanguinity rates are often cited for children referred with a major

congenital defect and compared with the equivalent cousin marriage rate in the


“general population”; the implication being that there is a causal relationship

between consanguinity and the expression of the defect(s) under investigation.

Unfortunately, in Arab populations with restricted effective population sizes and

strongly preferential clan and tribal endogamy, this type of comparison may fall far

short of the minimum requirement for rigorous case-control studies. Across gene-

rations, significant inter-clan, and more especially inter-tribal, genetic differences

could have arisen via founder effect and drift, and been amplified by intra-familial

marriage.

Several studies directly compared the prevalence of major congenital defects in

first-cousin and non-consanguineous progeny with, for example, an excess of 7.5%

(Jaber et al. 1992) and 6.1% at F¼ 0.0625 (Bromiker et al. 2004). The frequency of

consanguineous marriages was higher among the parents of offspring with congen-

ital malformations compared with the figures for the general population in virtually

all studies reported among Arabs, including the UAE (Al-Gazali et al. 1995;

Abdulrazzaq et al. 1997; Al Hosani et al. 2005; Dawodu et al. 2005), Kuwait

(Madi et al. 2005), Oman (Sawardekar 2005; Patel 2007), Iraq (Hamamy and

Al-Hakkak 1989; Mahdi 1992), Jordan (Khoury and Massad 2000; Obeidat et al.

2008), Egypt (Temtamy et al. 1998), Lebanon (Khlat 1988; Bittar 1998), Tunisia

(Khrouf et al. 1986) and Saudi Arabia (El Mouzan et al. 2008).

Elevated rates of consanguinity have been consistently reported for congenital

heart defects, in particular septal defects (Gev et al. 1986; Bassili et al. 2000;

Subramanyan et al. 2000; Becker et al. 2001; Nabulsi et al. 2003; Yunis et al.

2006; Seliem et al. 2007; El Mouzan et al. 2008), but for other heart defects such as

transposition of the great vessels and coarctation of the aorta, the results varied

between study centres, suggesting community-specific causes. Studies of neural

tube defects also showed positive associations with consanguinity (Zlotogora 1997;

Rajab et al. 1998; Al-Gazali et al. 1999; Murshid 2000; Asindi and Shehri 2001),

but for oral and facial clefts, the data were less consistent, with both a positive

association (Zlotogora 1997; Kanaan et al. 2008) and no association reported

(al-Bustan et al. 2002; Aljohar et al. 2008).

Consanguinity and Chromosome Aberrations

Following the initial report of an excess of Kuwaiti children with Down syndrome

born to consanguineous parents, a mechanism involving a recessively expressed

gene coding for non-disjunction of chromosome 21 was proposed (Alfi et al. 1980).

Additional support for this hypothesis was obtained from Kuwait (Naguib et al.

1989) and other non-Arab countries, but a number of subsequent studies in Arab

populations have been unable to identify the existence of a predisposing gene for

trisomy 21 (Hamamy et al. 1990; Zlotogora 1997; Chaabouni 1999; El Mouzan

et al. 2008). Some degree of uncertainty as to the possible predisposing role of

consanguinity remains, given the high rates of Down syndrome reported in Gulf


countries (Wahab et al. 2006), with conclusive results of either regional or global

application dependent on large-scale epidemiological studies incorporating control

for all appropriate non-genetic variables.

Consanguinity and Early Behavioural Disorders

Many early studies into possible adverse effects of consanguinity focused on

intellectual and developmental disability. In Arab populations, a significant but

modest negative association was demonstrated between consanguinity and mean

Intelligence Quotient (IQ) scores in children aged 10 years and 12 years, with the

lowest mean scores and highest variance in the progeny of double first cousins

(Bashi 1977). However, as previously discussed in other contexts, control for

variables other than consanguinity was incomplete, and this observation also

applies to studies that have reported an increased prevalence of speech disorders

(Jaber et al. 1997b), learning and reading difficulties (Eapen et al. 1998; Abu-Rabia

and Maroun 2005), hyperactivity (Al-sharbati et al. 2003), intellectual disability

(Al-Ansari 1993; Farag et al. 1993; Salem et al. 1994; Temtamy et al. 1994;

Abdulrazzaq et al. 1997), and recurrent febrile seizures (al-Eissa 1995) in first-

cousin and other consanguineous progeny.

Given the high overall rates of consanguineous marriages in Saudi Arabia, the

comparatively low level of intellectual disability (8.9/1,000) reported in Saudi

children aged 0–18 years was somewhat surprising (El-Hazmi et al. 2003). How-

ever, the authors noted that 83.2% of children with intellectual disability were not

attending school, which may have resulted in under-enumeration of affected chil-

dren. It is interesting that 70.9% of affected children were diagnosed with moderate

to severe intellectual disability (El-Hazmi et al. 2003), which suggests both a high

level of genetic causality and a significantly reduced life expectancy (Bittles et al.

2002b).

Consanguinity and Adult-Onset Disease

Limited information has been published on the effects of consanguinity on adult-

onset disorders among Arabs, with no significant differences in the prevalence or

the age of onset of diabetes mellitus, myocardial infarction, bronchial asthma or

duodenal ulcer in “consanguineous” and non-consanguineous subjects (Jaber et al.

1997c). As each of these conditions can be categorized as a complex disease, with

multiple potential interacting genes and environmental factors, and there was no

control for socioeconomic status or clan/tribe endogamy, the outcome is not

surprising.

Similar caveats apply to the confusing picture reported for adult cancers, with a

negative association between consanguinity and the overall risk of cancer (Denic

et al. 2007), both a lower breast cancer rate in women with consanguineous parents


(Denic and Bener 2001) and no effect of parental consanguinity on the risk of breast

cancer (Denic et al. 2005), and a hypothetical positive association between consan-

guinity and cervical cancer (Denic 2003). With life expectancy rapidly increasing

in most Arab countries, cancer can clearly be identified as a disease where well-

planned and rigorously conducted epidemiological studies are urgently needed.

Additional diagnostic problems may arise with adult behavioural disorders, and

until discrete disease phenotypes can be reproducibly demonstrated, the lack of a

significant association between consanguinity and schizophrenia reported in Sudan

(Ahmed 1979) and Saudi Arabia (Chaleby and Tuma 1987), and the positive

association of consanguinity with bipolar disease type 1 in Egypt (Mansour et al.

2009) merit acceptance with due caution. There is, however, convincing evidence

of specific predisposing genes for Alzheimer disease in an Israeli Arab village

isolate (Farrer et al. 2003), and it may be that studies that concentrate on individual

families and discrete communities, rather than surveys organised on a national or

regional basis, will prove to be the most rewarding in identifying individuals and

communities at high risk of complex diseases.

Genetic Counselling for Consanguineous Couples

Consanguinity is linked to ill-health, congenital malformations and intellectual

disability in the minds of many lay people in Arab countries. Often there is no

clear concept of how such conditions could be inherited, and the parents of affected

children may have difficulty in accepting a genetic explanation for diseases that did

not affect all of their children at the time of birth. Parents may also cite religious or

folk beliefs to account for illness, with denial or resignation to the situation, and

with divorce and remarriage accepted as possible solutions (Panter-Brick 1991;

Hamamy and Bittles 2009).

The belief that inherited disorders can arise only through cousin marriages on the

paternal side of the family is also quite common, as Arab societies are patrilineal

and in the minds of many people consanguinity may refer only to paternal blood

relationships. Thus, during counselling, if a couple indicate that they are not related,

it is imperative to specifically inquire about any shared biological relationships on

their mothers’ sides of the families. In similar vein, families may opt to avoid

cousin marriages when the disease is inherited as an autosomal dominant and are

bewildered by the subsequent birth of an affected baby.

Through school- and community-based education programmes and with improved,

non-invasive diagnostic facilities, younger couples in many Arab countries are

becoming increasingly aware of both the existence and the nature of genetic and

congenital disorders, and strategies to prevent their occurrence (Hamamy and

Alwan 1997; Alwan and Modell 1997). In Saudi Arabia, there is also strong

evidence that university students are aware of the availability of premarital screen-

ing for genetic disorders (Al-Aama et al. 2008).


Premarital Counselling

Premarital genetic counselling is a particularly important strategy in Arab commu-

nities. Despite a Fatwa issued by the Islamic Jurisprudence Council of the Islamic

World League that allowed abortion up to 120 days after conception in pregnancies

involving a foetus with a severe disorder or malformation not amenable to therapy

(Alkuraya and Kilani 2001; Albar 2002; Al Aqeel 2007), medical termination of

pregnancy is unacceptable on cultural, religious and legal grounds in many Arab

countries, Tunisia being an exception (Hessini 2007; Chaabouni-Bouhamed 2008).

In part, the reluctance to accept medical termination of pregnancy may reflect the

School of Islamic Jurisprudence to which an individual or community belongs

(Hamamy and Bittles 2009), besides differences in their cultural background and

community organisation (El-Hazmi 2007).

In many Arab countries, there are still inadequate numbers of appropriately

trained clinicians, midwives and nurses, genetic counsellors and laboratory person-

nel capable of providing full premarital genetic counselling coverage. In addition,

inconsistencies in genetic counselling protocols can arise, and guidelines on pre-

marital counselling for consanguineous couples are not generally available to health

care providers (Hamamy and Bittles 2009). Thus, an accurate risk estimate can-

not always be provided by a counsellor because of unknown population basal

parameters.

Premarital counselling is, nevertheless, an effective strategy for the prevention

of autosomal recessive conditions and can be of particular help in reducing the

numbers of arrangedmarriages of high-risk couples. Following premarital counselling,

even if couples had decided to proceed with marriage to a relative, a large majority

reported that the counselling had influenced their final decision to some degree

(Shiloh et al. 1995). Given the close structure of Arab families, premarital

counselling can also provide educational benefits to other members of the extended

family.

Premarital Screening and Carrier Testing

Community programmes for premarital screening to detect b-thalassaemia carriers

have been initiated in a number of Arab countries, including Jordan, Saudi Arabia,

Bahrain, UAE and Tunisia (Al Arrayed 2005; Al-Gazali et al. 2005; Al-Gazali et al.

2006; El-Hazmi 2006). Besides their intended purpose, the programmes have

additionally served to increase public awareness about genetic diseases in general

and specific disease prevention options, and have helped to reduce the fear that

consanguinity is a major risk factor in such disorders.

Problems can exist in terms of carrier testing, because of difficulty in diagnosing

the condition in the family, including the lack of a molecular diagnosis, the refusal

of affected family members to undergo testing, or the death of an affected person


before sampling could be arranged. In countries with a strong tradition of medical

paternalism, there may also be an expectation on the part of counsellees and their

families that directive advice will be given on issues such as the choice of a

marriage partner, reproductive options and medical termination of pregnancy

(WHO 2002; Rantanen et al. 2008; Hamamy and Bittles 2009). Unfortunately,

failure to provide such advice may be interpreted by families as a sign of self-doubt

and a lack of knowledge on the part of the clinician (Eldahdah et al. 2007).

As consanguineous marriage is a strong cultural belief, cousin couples may face

specific problems in conveying the diagnosis of their disorder to other family

members whose own future marital arrangements may be jeopardised. Some

couples also express dissatisfaction when offered a percentage risk estimate rather

than a definitive diagnostic opinion (Hamamy and Bittles 2009). Even though a

decision not to proceed with an arranged marriage is taken voluntarily by the family

on the grounds of a high risk to future offspring, in communities with a strong

patrilineal and patrilocal tradition some stigmatisation may be directed at the

female partner (Raz and Atar 2004).

Conclusions

With increasing urbanisation, improved access to higher education, professional

employment and wider social networks, some decline in the occurrence of arranged

and consanguineous marriages seems probable, especially in the Arab diaspora.

As previously indicated, this trend is underway in many, but by no means all, Arab

countries, and in Arab societies in general consanguineous marriage remains

culturally and socially respected.

Many Arab countries are experiencing demographic transitions, including a

substantial reduction in infant mortality rates. Therefore, it is important that action

be taken to improve the education and training of Arab health care providers on

issues concerning consanguineous marriage. As infant mortality rates decline, the

proportion of ill-health and early deaths due to genetic and congenital disorders

increases (Bittles 1995, 2001), necessitating robust, comprehensive national pro-

grammes for the control of inherited disorders.

The need for a better understanding of the potential association between consan-

guinity and genetic disorders is crucial in Arab countries where up to 50% of all

marriages may be intra-familial (Table 4.1). To date, there has been limited

appreciation of the very important role and consequences of clan and tribal sub-

divisions in the transmission of disease genes, resulting in an over-emphasis of the

adverse role of consanguinity. In populations that are sub-divided along ethnic,

religious, clan and tribal lines, a recessive founder or de novo mutation of chronic

effect can rapidly increase in frequency within a particular community. Hence, with

the strict patterns of clan and tribe endogamy that still apply in most Arab societies,

a child may have inherited a specific recessive disorder irrespective of whether its

parents are consanguineous or non-relatives (Zlotogora et al. 2006).


Clear examples of community endogamy are seen in the distribution of tribe-

specific single-gene disorders in Saudi Arabia, for example, maple syrup urine

disease, methylmalonic acidaemia, Sandhoff disease and Canavan disease (Ozand

et al. 1990; Ozand et al. 1992; Rashed et al. 1994). Likewise, in an Israeli Arab

village of 8,600 inhabitants, 19 mostly chronic autosomal recessive disorders have

been identified with a prevalence of known and suspected AR disorders of 1/70

(Zlotogora et al. 2000). Different villages may exhibit quite different disease

profiles, and the levels of village endogamy and consanguinity in some Arab

communities are such that, even within a single village, it has been possible to

identify and plot the origins and expansion patterns of four different b-globinmutations (Zlotogora et al. 2005), with no suggestion that this situation is unique

to the study community. There is also a significantly increased chance that more

than one detrimental recessive gene may be expressed in a family (Gordon et al.

1990), which can cause major difficulties in the provision of genetic counselling.

Failure to recognise the significant role of population stratification in the preva-

lence and distribution patterns of genetic disorders has serious implications for

genetic education and genetic counselling programmes. Subject to ethical conside-

rations, in many cases the clan or tribe may be the most logical unit of population

for interventions based on population screening and genetic counselling, since in

effect each acts as a separate and largely discrete gene pool (Bittles 2008). This

opinion is exemplified by the distribution pattern of b-thalassaemia in Oman. Of the

estimated 185 major Omani tribes and sub-tribes, only some 10% of tribes are

affected by b-thalassaemia and over 50% of all cases were diagnosed in a single

tribe (Rajab and Patton 1997, 1999).

Under these circumstances, the selection of subjects for case–control studies,

association studies and clinical trials becomes critical. More specifically, in the

investigation of consanguinity outcomes, comparisons drawn between the progeny

of couples selected solely in terms of their current marital relationships will be of

dubious validity unless they are members of the same tribe and clan (Bittles 2008).

Conversely, where there is evidence of both consanguinity and family clustering, as

in a study of male factor infertility in Lebanon (Inhorn et al. 2008), the associations

drawn become much more persuasive.

Given their particular family, clan and tribal structures, high rates of consan-

guineous marriage, large kindred size, and in many countries access to rapidly

advancing health facilities, it can be expected that Arab populations will continue to

be a major focus for research in medical and community genetics. The Arab

Genetic Disease Database (Teebi et al. 2002) and the Catalogue of Transmission

Genetics in Arabs established by the Centre for Arab Genomic Studies (Tadmouri

et al. 2006) will greatly assist this progress and improve our knowledge of the

underlying disease genomics and phenotypes.

It is essential that equivalent emphasis be devoted to the investigation of the

cultural, social and economic attributes of consanguineous unions, and the advan-

tages that make them attractive marital options to families. With socioeconomic

progress, the balance between the advantages and disadvantages of consanguinity is

changing, and many infants with a genetic disorder who in earlier generations


would have died at a young age will survive into adulthood (Bittles 2001). A radical

shift in disease impact of this nature places parents and the extended family in an

invidious position with respect to future family marriage prospects and arrange-

ments. There is evidence of the difficulties faced by families in arranging marriages

with non-relatives, when multiple family members are affected by a serious inher-

ited health disorder (Jalili and Smith 1988; Basel-Vanagaite et al. 2007). For such

families, the only realistic option may be to resort to even higher rates of intra-

familial marriage, with the probability that equivalently increased numbers of

affected offspring will be born.

Against this background, the importance of genetic education and premarital

genetic counselling programmes becomes increasingly obvious and effective in

social, economic and health terms. Especially since it is probable that endogamy

and consanguinity will be shown to play significant roles in the aetiology of many

complex diseases, including common major disorders of adult-onset. It is impera-

tive that programmes of this type, appropriate in design, structure and content to

meet the needs of Arab communities, be developed and introduced as an issue of

high priority.

References

Abdulrazzaq YM, Bener A, Al-Gazali LI, Al-Khayat AI, Micallef R, Gaber T (1997) A study of

possible deleterious effects of consanguinity. Clin Genet 51:167–173

Abolfotouh MA, Nofal LM, Safwat H (1990) Growth and nutritional status of preschool children

attending the well-baby clinics. J Egypt Public Health Assoc 65:485–507

Abu-Rabia S, Maroun L (2005) The effect of consanguineous marriage on reading disability in the

Arab community. Dyslexia 11:1–21

Ahmed AH (1979) Consanguinity and schizophrenia in Sudan. Brit J Psychiat 134:635–636

Al Aqeel A (2007) Islamic ethical framework for research into and prevention of genetic diseases.

Nat Gen 39:1293–1298

Al Arrayed S (1994) Consanguinity in the state of Bahrain. In: El-Hazmi MAF (ed) Medical

genetics in the setting of Middle Eastern populations. King Abdul Aziz City for Science and

Technology, Riyadh, pp 97–101

Al Arrayed S (2005) Campaign to control genetic blood diseases in Bahrain. Community Genet

8:52–55

Al Hosani H, Salah M, Abu-Zeid H, Farag HM, Saade D (2005) The national congenital anomalies

register in the United Arab Emirates. East Mediterr Health J 11:690–699

al Husain M, al Bunyan M (1997) Consanguineous marriages in a Saudi population and the effect

of inbreeding on prenatal and postnatal mortality. Ann Trop Paediatr 17:155–160

Al-Aama JY, Al-Nabulsi BK, Alyousef MA, Asiri NA, Al-Blewi M (2008) Knowledge regarding

the national premarital screening program among university students in western Saudi Arabia.

Saudi Med J 29:1649–1653

al-Abdulkareem AA, Ballal SG (1998) Consanguineous marriage in an urban area of Saudi Arabia:

rates and adverse health effects on the offspring. J Commun Health 23:75–83

al-Ansari A (1993) Etiology of mild mental retardation among Bahraini children: a community-

based case control study. Ment Retard 31:140–143

Al-Awadi S, Moussa MA, Naguib KK, Farag TI, Teebi AS, el-Khalifa M, el-Dossary L (1985)

Consanguinity among the Kuwaiti population. Clin Genet 27:483–486


Al-Awadi SA, Naguib KK, Moussa MA, Farag TI, Teebi AS, el-Khalifa MY (1986) The effect of

consanguineous marriages on reproductive wastage. Clin Genet 29:384–388

Albar M (1999) Counselling about genetic disease: an Islamic perspective. East Mediterr Health J

5:1129–1133

Albar M (2002) Ethical considerations in the prevention and management of genetic disorders with

special emphasis on religious considerations. Saudi Med J 23:627–632

al-Bustan SA, el-Zawahri MM, al-Adsani AM, Bang RL, Ghunaim I, Maher BS, Weinberg S,

Marazita ML (2002) Epidemiological and genetic study of 121 cases of oral clefts in Kuwait.

Orthod Craniofac Res 5:154–160

al-Eissa YA (1995) Febrile seizures: rate and risk factors of recurrence. J Child Neurol 10:315–319

al-Eissa YA, Ba’Aqeel HS, Haque KN (1991) Low birthweight in Riyadh, Saudi Arabia: incidence

and risk factors. Ann Trop Paediatr 11:75–82

Alfi O, Chang R, Azen S (1980) Evidence for genetic control of nondisjunction in man. Am J Hum

Genet 32:477–483

Al-Gazali LI (1998) A genetic aetiological survey of severe childhood deafness in the United Arab

Emirates. J Trop Ped 44:157–160

Al-Gazali LI, Dawodu AH, Sabarinathan K, Varghese M (1995) The profile of major congenital

abnormalities in the United Arab Emirates (UAE) population. J Med Genet 32:7–13

Al-Gazali LI, Bener A, Abdulrazzaq YM, Micaleff R, Al-Khayat GT (1997) Consanguineous

marriages in the United Arab Emirates. J Biosoc Sci 29:491–497

Al-Gazali LI, Sztriha L, Dawodu A, Bakir M, Varghese M, Varady E, Scorer J, Abdulrazzaq YM,

Bener A, Padmanabhan R (1999) Pattern of central nervous system anomalies in a population

with a high rate of consanguineous marriages. Clin Genet 55:95–102

Al-Gazali LI, Alwash R, Abdulrazzaq YM (2005) United Arab Emirates: communities and

community genetics. Community Genet 8:186–196

Al-Gazali L, Hamamy H, Al-Arrayad S (2006) Genetic disorders in the Arab world. Brit Med J

333:831–834

Al-Idrissi I, Al-Kaff AS, Senft SH (1992) Cumulative incidence of retinoblastoma in Riyadh,

Saudi Arabia. Ophthal Paediat Genet 13:9–12

Aljohar A, Ravichandran K, Subhani S (2008) Pattern of cleft lip and palate in hospital-based

population in Saudi Arabia: retrospective study. Cleft Palate Craniofac J 45:592–596

Alkuraya FS, Kilani RA (2001) Attitude of Saudi families affected with hemoglobinopathies

towards prenatal screening and abortion and the influence of religious ruling (Fatwa). Prenat

Diagn 21:448–461

Al-Salem M, Rawashdeh N (1993) Consanguinity in North Jordan: prevalence and pattern.

J Biosoc Sci 25:553–556

Al-sharbati MM, Al-Hussaini AA, Anthony SX (2003) Profile of child and adolescent psychiatry

in Oman. Saudi Med J 24:391–395

Al-Thakeb FT (1985) The Arab family and modernity: evidence from Kuwait. Curr Anthropol

26:575–580

Alwan A, Modell B (1997) Community control of genetic and congenital disorders, EMRO

Technical Publications 24. World Health Organization, Alexandra

Alwan A, Modell B (2003) Recommendations for introducing genetics services in developing

countries. Nat Rev Genet 4:61–68

Asindi A, Shehri A (2001) Neural tube defects in the Asir region of Saudi Arabia. Ann Saudi Med

21:26–29

Assaf S, Khawaja M (2009) Consanguinity trends and correlates in the Palestinian Territories.

J Biosoc Sci 41:107–124

Assaf S, Khawaja M, DeJong J, Mahfoud Z, Yunis K (2009) Consanguinity and reproductive

wastage in the Palestinian territories. Paediatr Perinat Epidemiol 23:107–115

Attias J, Al-Masri M, Abukader L, Cohen G, Merlov P, Pratt H, Othman-Jebara R, Aber P, Raad F,

Noyek A (2006) The prevalence of congenital and early-onset hearing loss in Jordanian and

Israeli infants. Int J Audiol 45:528–536


Basel-Vanagaite L, Taub E, Halpern GJ, Drasinover V, Magal N, Davodov B, Zlotogora J,

Shohat M (2007) Genetic screening for autosomal recessive nonsyndromic mental retardation

in an isolated population in Israel. Eur J Hum Genet 15:250–253

Bashi J (1977) Effects of inbreeding on cognitive performance. Nature 266:440–442

Bassili A, Mokhtar SA, Dabous NI, Zaher SR, Mokhtar MM, Zaki A (2000) Risk factors for

congenital heart diseases in Alexandria, Egypt. Eur J Epidemiol 16:805–814

Becker SM, Al Halees Z, Molina C, Paterson RM (2001) Consanguinity and congenital heart

disease in Saudi Arabia. Am J Med Genet 99:8–13

Benallegue A, Kedji F (1984) Consanguinite et sante publique: Etude algerienne. Arch Fr Pediatr

41:435–440

Bener A, Alali KA (2006) Consanguineous marriage in a newly developed country: the Qatari

population. J Biosoc Sci 38:239–246

Bener A, Abdulrazzaq YM, Al-Gazali LI, Micallef R, Al-Khayat AI, Gaber T (1996) Consangui-

noity and associated socio-demographic factors in the United Arab Emirates. Hum Hered

46:256–264

Bittar Z (1998) Major congenital malformations presenting in the first 24 hours of life in 3865

consecutive births in south of Beirut. Incidence and pattern. J Med Liban 46:256–260

Bittles AH (1995) When cousins marry: consanguineous marriage in the Middle East. Perspect

Hum Biol 1:71–83

Bittles AH (2001) Consanguinity and its relevance to clinical genetics. Clin Genet 60:89–98

Bittles AH (2005) Endogamy, consanguinity and community disease profiles. Commun Genet

8:17–20

Bittles AH (2008) A community genetics perspective on consanguineous marriage. Commun

Genet 11:324–330

Bittles AH, Grant JC, Sullivan S, Hussain R (2002a) Does inbreeding lead to decreased human

fertility? Ann Hum Biol 29:111–131

Bittles AH, Petterson BA, Sullivan S, Hussain R, Glasson EJ, Montgomery PD (2002b)

The influence of intellectual disability on life expectancy. J Gerontol A: Biol Sci Med Sci

57A:M470–M472

Bromiker R, Glam-Baruch M, Gofin R, Hammerman C, Amitai Y (2004) Association of parental

consanguinity with congenital malformations among Arab newborns in Jerusalem. Clin Genet

66:63–66

Chaabouni H (1999) Etude epidemiologique et genetique de la trisomie 21 en Tunisie. Tunisie Me

77:407–414

Chaabouni-Bouhamed H (2008) Tunisia: communities and community genetics. Community

Genet 11:313–323

Chaleby K (1988) Traditional Arabian marriages and mental health in a group of outpatient

Saudis. Acta Psychiatr Scand 77:139–142

Chaleby K, Tuma TA (1987) Cousin marriages and schizophrenia in Saudi Arabia. Brit J Psychiatr

150:547–549

Christianson A, Howson C, Modell B (2006) Global report on birth defects. The hidden toll of

dying and disabled children. March of Dimes Birth Defects Foundation, White Plains, NY

COSIT, Central Organization for Statistics and Information Technology (2005) Iraq living

conditions survey 2004, vol. II: Analytical Report. Ministry of Planning and Development

Cooperation, Baghdad

Dawodu A, Al-Gazali L, Varady E, Varghese M, Nath K, Rajan V (2005) Genetic contribution to

high neonatally lethal malformation rate in the United Arab Emirates. Community Genet

8:31–34

Denic S (2003) Consanguinity as a risk factor for cervical carcinoma. Med Hypoth 60:321–324

Denic S, Bener A (2001) Consanguinity decreases risk of breast cancer – cervical cancer

unaffected. Brit J Cancer 85:1675–1679

Denic S, Bener A, Sabri S, Khatib F, Milenkovic J (2005) Parental consanguinity and risk of breast

cancer: a population-based case-control study. Med Sci Monit 11:CR415–CR419


Denic S, Frampton C, Nicholls MG (2007) Risk of cancer in an inbred population. Cancer Detect

Prev 31:263–269

Eapen V, Al-Gazali L, Bin-Othman S, Abou-Saleh M (1998) Mental health problems among

schoolchildren in United Arab Emirates: prevalence and risk factors. J Am Acad Child Adolesc

Psychiatr 37:880–886

El Mouzan MI, Al Salloum AA, Al Herbish AS, Qurachi MM, Al Omar AA (2008) Consanguinity

and major genetic disorders in Saudi children: a community-based cross-sectional study. Ann

Saudi Med 28:169–173

El-Badramany MH, Farag TI, Al-Awadi SA, Teebi AS (1997) Psychosocial and medical aspects of

genetic counseling among Arabs: the example of Kuwait. In: Teebi AS, Farag TI (eds) Genetic

disorders among Arab populations, vol 1. Oxford University Press, New York, pp 474–486

Eldahdah L, Ormond K, Nassar A, Khalil T, Zahed L (2007) Outcome of chromosomally abnormal

pregnancies in Lebanon: obstetricians’ roles during and after prenatal diagnosis. Prenat Diagn

27:525–534

Elder MJ, De Cock R (1993) Childhood blindness in the West Bank and the Gaza Strip:

prevalence, aetiology and hereditary factors. Eye 7:580–583

El-Hazmi MA (2006) Pre-marital examination as a method of prevention from blood genetic

disorders. Community views. Saudi Med J 27:1291–1295

El-Hazmi M (2007) Islamic teachings of bioethics in relation to the practice of medical genetics.

Saudi Med J 28:1781–1787

El-Hazmi M, Al-Swailem AA, Warsy A, Al-Swailem AM, Sulaimani R, Al-Meshari A (1995)

Consanguinity among the Saudi Arabian population. J Med Genet 32:623–626

El-Hazmi M, Al-Swailem AA, Al-Mosa NA, Al-Jarallah AA (2003) Prevalence of mental

retardation among children in Saudi Arabia. East Mediterr Health J 9:6–11

El-Islam MF (1976) Intergenerational conflict and the young Qatari neurotic. Ethos 4:45–56

El-Mouzan MI, Al-Salloum AA, Al-Herbish AS, Qurachi MM, Al-Omar AA (2007) Regional

variations in the prevalence of consanguinity in Saudi Arabia. Saudi Med J 28:1881–1884

Farag TI, Al-Awadi SA, el-Badramany MH, Aref MA, Kasrawi B, Krishna Murthy DS et al (1993)

Disease profile of 400 institutionalized mentally retarded patients in Kuwait. Clin Genet

44:329–334

Farrer LA, Bowirrat A, Friedland RP, Waraska K, Korczyn AD, Baldwin CT (2003) Identification

of multiple loci for Alzheimer loci in a consanguineous Israeli-Arab community. Hum Mol

Genet 12:415–422

Freundlich E, Hino N (1984) Consanguineous marriage among rural Arabs in Israel. Isr J Med Sci

20:1035–1038

Gev D, Roguin N, Freundlich E (1986) Consanguinity and congenital heart disease in the rural

Arab population in northern Israel. Hum Hered 36:213–217

Gordon CR, Bar-Ziv Y, Frydman M, Zlotogora J, Gadoth N (1990) Mucolipidosis III and Bardet-

Biedl syndrome in the same family: diagnostic pitfalls. Brain Dev 12:403–407

Gunaid AA, Ali Hummad N, Tamim KA (2004) Consanguineous marriage in the capital city

Sana’a, Yemen. J Biosoc Sci 36:111–121

Hafez M, El-Tahan H, Awadalla M, El-Khayat H, Abdel-Gafar A, Ghoneim M (1983) Consan-

guineous matings in the Egyptian population. J Med Genet 20:58–60

Hamamy H, Al-Hakkak Z (1989) Consanguinity and reproductive health in Iraq. Hum Hered

39:271–275

Hamamy H, Alwan A (1994) Hereditary disorders in the Eastern Mediterranean Region. Bull

World Health Organ 72:45–154

Hamamy H, Alwan A (1997) Genetic disorders and congenital abnormalities: strategies for

reducing the burden in the region. East Mediterr Health J 3:123–132

Hamamy H, Bittles AH (2009) Genetic clinics in Arab communities: meeting individual, family

and community needs. Public Health Genomics 12:30–40

Hamamy HA, al-Hakkak ZS, al-Taha S (1990) Consanguinity and the genetic control of Down

syndrome. Clin Genet 37:24–29


Hamamy H, Jamhawi L, Al-Darawsheh J, Ajlouni K (2005) Consanguineous marriages in Jordan:

why is the rate changing with time? Clin Genet 67:511–516

Hamamy H, Al-Hait S, Alwan A, Ajlouni K (2007a) Jordan: communities and community

genetics. Commun Genet 10:52–60

Hamamy HA, Masri AT, Al-Hadidy AM, Ajlouni KM (2007b) Consanguinity and genetic

disorders. Profile from Jordan. Saudi Med J 28:1015–1017

Hammami A, Chalbi N, Ben Abdallah M, Elgazzeh M (2005) Effects of consanguinity and social

factors on mortality and fertility in Mauritania. Tunis Med 83:221–226

Hessini L (2007) Abortion and Islam: policies and practice in the Middle East and North Africa.

Reprod Health Matters 15:1–10

Hoodfar E, Teebi AS (1996) Genetic referrals of Middle Eastern origin in a western city:

inbreeding and disease profile. J Med Genet 33:212–215

Hussain R (1999) Community perceptions of reasons for preference for consanguineous marriages

in Pakistan. J Biosoc Sci 31:449–461

Hussien FH (1971) Endogamy in Egyptian Nubia. J Biosoc Sci 3:251–257

Inhorn MC, Kobeissi L, Nassar Z, Lakkis D, Fakih MH (2008) Consanguinity and family

clustering of male factor infertility in Lebanon. Fertil Steril (Epub ahead of print)

Jaber L, Merlob P, Bu X, Rotter JI, Shohat M (1992) Marked parental consanguinity as a cause for

increased major malformations in an Israeli Arab community. Am J Med Genet 44:1–6

Jaber L, Shohat T, Halpern GJ (1996) Demographic characteristics of the Israeli Arab community

in connection with consanguinity. Isr J Med Sci 32:1286–1289

Jaber L, Merlob P, Gabriel R, Shohat M (1997a) Effects of consanguineous marriage on reproduc-

tive outcome in an Arab community in Israel. J Med Genet 34:1000–1002

Jaber L, Nahmani A, Shohat M (1997b) Speech disorders in Israeli Arab children. Isr J Med Sci

33:663–665

Jaber L, Shohat T, Rotter JI, Shohat M (1997c) Consanguinity and common adult diseases in

Israeli Arab communities. Am J Med Genet 70:346–348

Jaber L, Halpern GJ, Shohat T (2000) Trends in the frequencies of consanguineous marriages in

the Israeli Arab community. Clin Genet 58:106–110

Jalili IK, Smith NJD (1988) A progressive cone-rod dystrophy and amelogenesis imperfecta:

a new syndrome. J Med Genet 25:738–740

Joseph SE (2007) “Kissing coins”: consanguineous marriage and early mortality in a reproductive

isolate. Curr Anthropol 48:756–764

Jurdi R, Saxena PC (2003) The prevalence and correlates of consanguineous marriages in Yemen:

similarities and contrasts with other Arab countries. J Biosoc Sci 35:1–13

Kanaan ZM, Mahfouz R, Tamim H (2008) The prevalence of consanguineous marriages in an

underserved area in Lebanon and its association with congenital anomalies. Genet Test

12:367–372

Kerkeni E, Kerkeni E, Monastiri K, Saket B, Guediche MN, Ben Cheikh H (2007) Interplay of

socio-economic factors, consanguinity, fertility, and offspring mortality in Monastir, Tunisia.

Croat Med J 48:701–707

Khabori MA, Patton MA (2008) Consanguinity and deafness in Omani children. Int J Audiol

47:30–33

Khawaja M, Tewtel-Salem M (2004) Agreement between husband and wife reports of domestic

violence: evidence from poor refugee communities in Lebanon. Int J Epidemiol 33:526–533

Khlat M (1985) Consanguineous marriages in Beirut: time trends, spatial distribution. Soc Biol

35:324–330

Khlat M (1988) Consanguineous marriage and reproduction in Beirut, Lebanon. Am J Hum Genet

43:188–196

Khlat M (1989) Inbreeding effects on fetal growth in Beirut, Lebanon. Am J Phys Anthropol

80:481–484

Khlat M (1997) Endogamy in the Arab world. In: Teebi AS, Farag TI (eds) Genetic disorders

among Arab populations, 1st edn. Oxford University Press, New York, pp 63–80


Khlat M, Halabi S, Khudr A, Der Kaloustian VM (1986) Perception of consanguineous

marriages and their genetic effects among a sample of couples from Beirut. Am J Med

Genet 25:299–306

Khoury SA, Massad D (1992) Consanguineous marriage in Jordan. Am J Med Genet

43:769–775

Khoury SA, Massad D (2000) Consanguinity, fertility, reproductive wastage, infant mortality and

congential malformations in Jordan. Saudi Med J 21:150–154

Khrouf N, Spang R, Podgorna T, Miled SB, Moussaoui M, Chibani M (1986) Malformations in

10, 000 consecutive births in Tunis. Acta Pediatr Scand 75:534–539

Khuri FI (1970) Parallel cousin marriage reconsidered: a Middle Eastern practice that nullifies the

effects of marriage on the intensity of familial relationships. Man 5:597–618

Klat M, Khudr A (1986) Religious endogamy and consanguinity in marriage patterns in Beirut,

Lebanon. Soc Biol 33:138–145

Lamdouar Bouazzaoui N (1994) Consanguinite et sante publique au Maroc. Bull Acad Natl Med

178:1013–1027

Maatouk F, Laamri D, Argoubi K, Ghedra H (1995) Dental manifestations of inbreeding. J Clin

Pediatr Dent 19:305–306

Madi SA, Al-Naggar RL, Al-Awadi SA, Bastaki LA (2005) Profile of major congenital malforma-

tions in neonates in Al-Jahra region of Kuwait. East Mediterr Health J 11:700–706

Mahdi A (1992) Consanguinity and its effect on major congenital malformations. Iraqi Med J

40–42:70–176

Mansour H, Klei L, Wood J, Talkowski M, Chowdari K, Fathi W et al (2009) Consanguinity

associated with increased risk for bipolar 1 disorder in Egypt. Am J Med Genet Part B:

Neuropsychiatr Genet 150:879–885

Maziak W, Asfar T (2003) Physical abuse in low-income women in Aleppo, Syria. Health Care

Women Int 24:313–326

Mokhtar MM, Abdel-Fattah MM (2001) Consanguinity and advanced maternal age as risk factors

for reproductive losses in Alexandria, Egypt. Eur J Epidemiol 17:559–565

Mumtaz G, Tamim H, Kanaan M, Khawaga M, Khogali M, Wakim G, Yunis K (2007) Effect of

consanguinity on birth weight for gestational age in a developing country. Am J Epidemiol

165:742–752

Murshid WR (2000) Spina bifida in Saudi Arabia: is consanguinity among the parents a risk

factor? Pediatr Neurosurg 32:10–12

Nabulsi A (1995) Mating patterns of the Abbad tribe in Jordan. Soc Biol 42:162–174

Nabulsi MM, Tamim H, Sabbagh M, Obeid MY, Yunis KA, Bitar FF (2003) Parental consan-

guinity and congenital heart malformations in a developing country. Am J Med Genet A

116A:342–347

Naguib K, Al-Awai S, Moussa M, Farag T, Teebi A (1989) Effect of parental age, birth order and

consanguinity on nondisjunction in the population of Kuwait. J Kuwait Med Assoc 23:37–43

Nelson J, Smith M, Bittles AH (1997) Consanguineous marriage and its clinical consequences in

migrants to Australia. Clin Genet 52:142–146

Obeidat BR, Khader YS, Amarin ZO, Kassawneh M, Al Omari M (2008) Consanguinity and

adverse pregnancy outcomes: the north of Jordan experience. Matern Child Health J

[E-publication]

Ozand PT, Gascon GC, al Aqeel A, Roberts G, Dhalla M, Subramanyam SB (1990) Prevalence of

different types of lysosomal storage diseases in Saudi Arabia. J Inherit Dis 13:849–861

Ozand PT, Devol EB, Gascon GC (1992) Neuro-metabolic diseases at a national referral center:

five years experience at the King Faisal Specialist Hospital and Research Centre. J Child

Neurol 7(Suppl):S4–S11

Panter-Brick C (1991) Parental responses to consanguinity and genetic disease in Saudi Arabia.

Soc Sci Med 33:1295–1302

Patel PK (2007) Profile of major congenital anomalies in the Dhahira region, Oman. Ann Saudi

Med 27:106–111


Pedersen J (2002) The influence of consanguineous marriage on infant and child mortality among

Palestinians in the West Bank and Gaza, Jordan, Lebanon and Syria. Community Genet

5:178–181

Radovanovic Z, Shah N, Behbehani J (1999) Prevalence and social correlates of consanguinity in

Kuwait. Ann Saudi Med 19:206–210

Rajab A, Patton MA (1997) Major factors determining the frequencies of hemoglobinopathies in

Oman. Am J Med Genet 71:240–242

Rajab A, Patton MA (1999) Analysis of the population structure in Oman. Community Genet

2:23–25

Rajab A, Patton MA (2000) A study of consanguinity in the Sultanate of Oman. Ann Hum Biol

27:321–326

Rajab A, Vaishnav A, Freeman NV, Patton MA (1998) Neural tube defects and congenital

hydrocephalus in the Sultanate of Oman. J Trop Pediatr 44:300–303

Rantanen E, Hietala M, Kristoffersson U, Nippert I, Schmidtke J, Swequeiros J, K€a€ari€ainen H

(2008) What is ideal genetic counselling? A survey of current international guidelines. Eur

J Hum Genet 16:445–452

Rashed M, Ozand PT, Al Aqeel A, Gascon GG (1994) Experience of King Faisal Hospital and

Research Centre with Saudi organic acid disorders. Brain Dev 16(Suppl):1–6

Raz AE, Atar M (2004) Cousin marriage and premarital carrier matching in a Bedouin community

in Israel: attitudes, service development and educational intervention. J Fam Plann Reprod

Health Care 30:49–51

Riou SE, Younsi C, Chaabouni H (1989) Consanguinite dans la population du Nord de la Tunisie.

Tunis Med 67:167–172

Saad FA, Jauniaux E (2002) Recurrent early pregnancy loss and consanguinity. Reprod Biomed

Online 5:167–170

Saedi-Wong S, al-Frayh AR (1989) Effects of consanguineous matings on anthropometric

measurements of Saudi newborn infants. Fam Pract 6:217–220

Saedi-Wong S, al-Frayh AR, Wong HYH (1989) Socio-economic epidemiology of consanguineous

mating in the Saudi Arabian population. J Asian Afr Stud 24:247–251

Saha N, El Sheikh FS (1988) Inbreeding levels in Khartoum. J Biosoc Sci 20:333–336

Saha N, Hamad RE, Mohamed S (1990) Inbreeding effects on reproductive outcome in a Sudanese

population. Hum Hered 40:208–212

Salem K, Lashin S, El Dib A (1994) Consanguinity and mental retardation. Med J Cairo Univ 62

(Suppl):177–186

Sawardekar KP (2005) Profile of major congenital malformations at Nizwa Hospital, Oman:

10-year review. J Paediatr Child Health 41:323–330

Seliem MA, Bou-Holaigah IH, Al-Sannaa N (2007) Influence of consanguinity on the pattern of

familial aggregation of congenital cardiovascular anomalies in an outpatient population:

studies from the eastern province of Saudi Arabia. Community Genet 10:27–31

Sharkia R, Zaid M, Athamna A, Cohen D, Azem A, Zalan A (2007) The changing pattern of

consanguinity in a selected region of the Israeli Arab community. Am J Hum Biol 20:72–77

Shiloh S, Reznik H, Bat-Miriam-Katznelson M, Goldman B (1995) Pre-marital genetic

counselling to consanguineous couples: attitudes, beliefs and decisions among counselled,

noncounselled and unrelated couples in Israel. Soc Sci Med 41:1301–1310

Stern GH (1939) Marriage in early Islam. London, The Royal Asiatic Society, pp 165–166

Subramanyan R, Joy J, Venugopalan SA, Al Khusaiby SM (2000) Incidence and spectrum of

congenital heart disease in Oman. Ann Trop Paediatr 20:337–340

Tadmouri GO, Al Ali MT, Al-Haj Ali S, Al Khaja N (2006) CTGA: the database for genetic

disorders in Arab populations. Nucleic Acids Res 34(Database issue):D602–606

Tamim H, Khogali M, Beydoun H, Melki I, Yunis K (2003) Consanguinity and apnea of

prematurity. Am J Epidemiol 158:942–946

Teebi A (1994) Autosomal recessive disorders among Arabs: an overview from Kuwait. J Med

Genet 31:224–233


Teebi AS, Teebi SA, Porter CJ, Cuticchia AJ (2002) Arab genetic disease database (AGDDB):

a population-specific clinical and mutation database. Hum Mutat 19:615–621

Temtamy SA, Kandil MR, Demerdash AM, Hassan WA, Meguid NA, Afifi HH (1994) An

epidemiological/genetic study of mental subnormality in Assiut Governorate, Egypt. Clin

Genet 46:347–351

Temtamy S, Abdel Meguid N, Mazen I, Ismail S, Kassem N, Bassiouni R (1998) A genetic

epidemiological study of malformations at birth in Egypt. East Mediterr Health J 4:252–259

Tucker JE (1988) Marriage and family in Nablus, 1720–1856: toward a history of Arab marriage.

J Fam Hist 13:165–179

Vardi-Saliternik R, Friedlander Y, Cohen T (2002) Consanguinity in a population sample of Israeli

Muslim Arabs, Christian Arabs and Druze. Ann Hum Biol 29:422–431

Wahab AA, Bener A, Teebi AS (2006) The incidence patterns of Down syndrome in Qatar. Clin

Genet 69:360–362

WHO (2002) Advisory committee on health research, genomics and world health. World Health

Organization, Geneva

Wong SS, Anokute CC (1990) The effect of consanguinity on pregnancy outcome in Saudi Arabia.

J R Soc Health 110:146–147

Yunis K, Mumtaz G, Bitar F, Chamseddine F, Kassar M, Rashkidi J et al (2006) Consanguineous

marriage and congenital heart defects: a case-control study in the neonatal period. Am J Med

Genet A 140:1524–1530

Zakzouk S, El-Sayed Y, Bafaqeeh SA (1993) Consanguinity and hereditary hearing impairment

among Saudi population. Ann Saudi Med 13:447–450

Zaoui S, Biemont C (2002) Frequence et structure des mariages consanguins dans le region de

Tlemcen (Ouest algerien). Cahiers Sante 12:289–295

Zlotogora J (1997) Genetic disorders among Palestinian Arabs: 1. Effects of consanguinity. Am

J Med Genet 68:472–475

Zlotogora J, Shalev S, Habiballah H, Barjes S (2000) Genetic disorders among Palestinian Arabs:

3. Autosomal recessive in a single village. Am J Med Genet 92:343–345

Zlotogora J, Habiballa H, Odatalla A, Barges S (2002) Changing family structure in a modernizing

society: a study of marriage patterns in a single Muslim village in Israel. Am J Hum Biol

14:680–682

Zlotogora J, Hujerat Y, Zalman L, Barges S, Filon D, Koren A, Shalev SA, Chakravarti A (2005)

The origin and expansion of four different beta globin mutations in a single Arab village. Am

J Hum Biol 17:659–661

Zlotogora J, Hujerat Y, Barges S, Shalev SA, Chakravti A (2006) The fate of 12 recessive

mutations in a single village. Ann Hum Genet 71:202–208


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