Ghulam Abbas

BSc MBBS MSc (Sports Med)MRCS FRCS (Tr & Orth) PGHE

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Introduction

Basic Genetics

Research Evidence

Summary

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Marrying first cousin increases the risk ofchildren having genetic disorders pretermbirth and early death

Many people are unaware of this, orunderestimate the impact of the risks

The risk is up to 2 % in unrelated parents

Chance at least doubles if you marry your

first cousin

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Observation in the family or community

Historical facts – A royal pain in the genes

Published data

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Grew up in a small village

Left village in 1988

Medical camp 2009

Recognised children's tribes

looking at them, kept “pure”

Similar birth defects

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Reflection in plane journey

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Rejecting labor-savingtechnologies

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Religious persecutions

Large families are a blessing from God

Descend from about 200 founders

Higher incidences of genetic disorders

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Extinction of Habsburg Dynasty (1516–1700)

Marrying cousins or other blood relatives wasprevalent

The last king was Charles II

impotence/infertility

Alvarez et al 2009

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G×Einteraction

Health

Genetics

Environment

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1. Segregation

2. Dominance

3. Independentassortment

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A normal cell has two variants for a trait.

An egg or a sperm contains one variant randomly chosenfrom the two variants in each cell

If you have one variant for brown eyes (B) and one variantfor blue eyes (b) then each cell of your body will have Bband each egg or sperm will carry one of B or b chosenrandomly

B b

B BB Bb

b Bb bb

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Eggs

Sperm

If your two variants are different such as Bb, the traitassociated with only one of these will be visible (dominant)while the other will be hidden (recessive). For example B isdominant, b is recessive.

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B b

B BB Bb

b Bb bbEggs

Sperm

State of the two variants Observed characteristics

BB (both for brown eyes) Brown eyes

Bb (one for brown eyes, one for blue eyes) Brown eyes

bb (both for blue eyes) Blue eyes

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Simplified view of eye colour inheritance:

Brown dominant: BB, Bb

Blue recessive: bb

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Human eye colour

B b

B BB Bb

b Bb bbEggs

Sperm

Increase the likelihood of inheriting the samegenes from both parents

Gene diversity declines as compared torandom mating populations

Inheriting the same genes from both parentsincreases recessive diseases

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All papers published in English between April1, 1965, and April 1, 2013.

search terms

“congenital abnormalities/epidemiology”AND “consanguinity.”

cousin marriage / birth defects

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Identified 219 relevant scientific papers

28 papers primary data related to cousinmarriages

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Exclusion criteria Inclusion criteria

Studies with smallsize

Observational and nocontrol group

no corrections forother risk factors

Contemporary controlgroups

Blood related vUnrelated union

Su cient size toachieve statisticalsignificance

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13,776 pregnancies

Congenital anomalies 6.1 % (cousinmarriage) v 2.1% (non-cousin marriage)

Microcephaly and Congenital heart disease

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L. Charafeddine et al, 26 hospitals inLebanon

Paediatric and Perinatal Epidemiology, 2012,

65,402 births studies

1.8 fold increase in death rate beforedischarge in cousin marriage V non-cousinmarriage

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1.56 million births in Norway from 1967 to1993

Compared three groups (Both parents native,one native and first cousins)

Relative risk of congenital anomalies twice inchildren whose parents were first cousins

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Mumtaz et al, Am J Epidemiol 2010

39,745 livebirths

19 hospitals in Lebanon

1.6-fold net increased risk - infants of cousinmarriage

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Four Hospitals , Jerusalem

561 Arab newborns

Incidence of major congenital malformations

8.7% first cousin couples

7.1% all consanguineous couples

2.6% non-consanguineous couples

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There is a link between cousin marriage andbirth defects, preterm birth and early death

Risk between 2 to 4 times depending uponthe study and type of genetic disorder

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