Keywords |
| Consanguineous marriages, Non-consanguineous marriage, Congenital anomalies, Pedigree. |
Introduction |
| 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. |
| Subjects |
| 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). |
 |
 |
 |
 |
Results |
| 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). |
Discussion |
| 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. |
Conclusion |
| 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. |
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