ENVIRONMENTAL AND GENETIC FACTORS STUDY USING MULTIPLEX LIGATION DEPENDENT PROBE AMPLIFICATION AMONG CONGENTITAL HEART DISEASE CHILDREN

Abstract

Congenital heart disease (CHD) is the most common disorder among live births with an incidence of 10/1000 newborns. It is also considered a major cause of morbidity and mortality, especially when associated with extra cardiac malformations. CHD in combination with other malformations occurs in about 25% of the cases, many of them represent recognizable genetic syndromes. In most cases, the cause of CHD is multifactorial including environmental teratogens with genetic factors including mendelian and chromosomal abnormalities. The objectives of this work were to improve the diagnostic outcome of different genomic imbalances among children with CHD associated with extra cardiac malformations by using Multiplex Ligation Dependent Probe Amplification (MLPA) technique and to evaluate the role of environmental predisposing factors in the causation of CHD in those children through complete history taking including interview risk factor questionnaire. Forty patients with CHD and extra cardiac manifestations were examined using conventional cytogenetic analysis (CCA) and MLPA technique, using Micro deletion and Sub telomere kits. MLPA analysis showed abnormalities in 5 patients (12.5%) in the form of Williams syndrome (7q11.23 deletion), Digeorge syndrome (22q11.2 deletion), Wolf -Hirschhorn syndrome (4p16.3 deletion) and 2p5.3 duplication syndrome. Chromosomal Microarray (CMA) was conducted for one patient with characteristic facial features and normal MLPA results and showed an interstitial 2.27 Mb deletion of chromosome 2q22 including the entire ZEB2 gene causing Mowat Wilson syndrome. Environmental risk factor questionnaire revealed a maternal history of fever or infections in 47.5% with flu occurring in 42.5% , taking drugs in 37.5%; mostly antipyretic and antibiotics i n few cases, and it also showed that 67.5% of the mothers were overweight with 25% of them being obese. As regards to children delivery circumstances, 22.5% were born with asphyxia and cyanosis. Regarding paternal characteristic risk factors, 33% of the fathers gave history of occupational exposures to building materials, insecticides, heat and noise, fumes and detergents. Thirty percent of fathers and 15% of mothers gave a history of chronic diseases mostly in the form of hypertension and type 2 diabetes. About 63% and 13% of the fathers were cigarettes and shisha smokers respectively, while only two mothers smoked cigarettes and one smoked shisha. The conduction of larger analytical studies investigating the role of environmental and genetic factors can provide better understandings of gene/ environment interactions and predisposition to CHD. This can also help more understanding of the genetic pathophysiology of CHD and improve the prevention strategies through risk assessment, early diagnosis, targeted therapeutic procedures, and appropriate family counseling