Inbreeding and congenital heart disease

1. Inbreeding and congenital heart disease
The closure ,The worse

2. Consanguinity
All marriages between couples related as second cousins or closer are
regarded as consanguineous (derived from the Latin con sanguineus;
i.e. sharing the same blood).
Medical genetics

3. Make aware ,save life
• Consanguineous unions is susceptible to inherited CHD
• Consanguinity is known to contribute to recessive diseases
• Consanguinity increases the prevalence of CHD
• Most of the studies suffers for clear implication of consanguinity in
risking is confounded by sociodemographic ,epigenetic and multiple
factors
• In consanguineous unions ,at first cousin level and closer, risks more

4. Prevalence
Marital unions between close
biological kin are common in many
populations, especially in South,
Central and West Asia, and North
and sub-Saharan Africa, and in
migrant communities from those
regions now resident in Europe,
North America and Oceania. At least
10.4% of the current world
population of 7.0 billion persons are
consanguineous, with first cousin
marriages especially popular
Bittles AH, Black ML. Consanguinity,
human evolution, and complex
diseases. Proc Natl Acad Sci U S A.
2010;107(Suppl 1):1779–86.

5. Grey area
ASD and VSD are the most common CHD ,associated with
consanguinity because of these 2 are the most common CHD needs
further studies

6. Inbreeding and individual CHD
Atrioventricular septal defect
(AVSD), pulmonary atresia,
pulmonic stenosis, VSD, and ASD
were associated
Becker SM, Al Halees Z, Molina C, Paterson RM.
Consanguinity and congenital heart disease in Saudi
Arabia. Am J Med Genet. 2001;99:8–13.

7. Inbreeding and individual CHD
ASD and PDA were strongly
influenced by consanguinity
Ramegowda S, Ramachandra NB. Parental
consanguinity increases congenital heart diseases in
South India. Ann Hum Biol. 2006;33:519–528.

8. Inbreeding and individual CHD
VSD (OR 2.70, 95% CI 2.07–3.50)
and ASD (OR 2.87, 95% CI 1.85–
4.47)
Bassili A, Mokhtar SA, Dabous NI, Zaher SR,
Mokhtar MM, Zaki A. Risk factors for congenital
heart diseases in Alexandria, Egypt. Eur J
Epidemiol. 2000;16(9):805–814.

9. Inbreeding and individual CHD
First-cousin marriages: types of
CHD including aortic valvular
anomalies, ASD, and tetralogy of
Fallot (TOF), VSD, and pulmonic
stenosis.
Nabulsi MM, Tamim H, Sabbagh M, Obeid MY,
Yunis KA, Bitar FF. Parental consanguinity and
congenital heart malformations in a developing
country. Am J Med Genet A. 2003;116:342–347.

10. Consanguinity and congenital heart disease

11. Consanguinity and congenital heart disease

13. Recurrence risk
Recurrence risks for non-syndromic CHD often range from 2–6% in the
absence of an extended family history of CHD

14. Politics of multiple factors & polygenetic
• It is uncommon for isolated congenital heart disease to be inherited
in a classic Mendelian manner, most cases are assumed to be
complex. For such multifactorial diseases, the ability to discuss and
present precise risks to a concerned family is directly related to our
understanding of the basis of disease. Based on the studies reviewed
here, which are the best currently available, we still need to strive to
understand the relative contribution of genetics versus the
environment in congenital heart disease. If we can determine the
proportional effect of consanguinity on disease, this may help
determine the genetic contribution to a specific complex condition or
the comparative role of genetics versus environmental influences.

15. Epigenetic is a major confounder
Environmental factors
1. Blood flow are clearly important in early heart development
2. Teratogens: Rubella or alcohol can contribute to the risk of congenital heart
disease
3. A susceptible gene nourishes well in provoking environment

16. Single nucleotide polymorphisms (SNPs)
Determine the ethnic ancestry of an individual based on genetics alone,
and the application of next generation methodologies will greatly
increase this analytical capacity. Such genomic identity may be able to
more precisely estimate the degree of genetic relatedness and identify
consanguineous relationships that otherwise could have been missed
or miscategorized based on self-report.

17. Perspective
4 keys areas
A consanguineous union may result in a greater risk for congenital heart
disease
Educate healthcare providers and patients
Involve the whole family in counselling
It is preventable