Detection of chromosome 22q11 micro deletions among children with isolated congenital heart disease using PCR

ABSTRACT

Congenital heart disease [CHD] is the most common form of human birth defects, affecting 0.4% to 0.9% of all live-born neonates. It is the leading non-infectious cause of mortality in newborns. Nowadays echocardiogram plays an important role on the diagnosis. This procedure is able to identify a wide range of malformations. However, despite the advances in diagnosis and treatment of congenital heart malformations, our understanding of the causative mechanisms has been limited. Previous studies suggest that a substantial number of patients with CHD have a 22q11 deletion. The type of CHD observed is variable, but frequently there is involvement of the conotruncal anomalies. Chromosome 22q11 deletion syndrome can be inherited in an autosomal dominant fashion or result from a de novo deletion or translocation. Therefore, early diagnosis of this syndrome is important both for management of the patient and for assessing risk of recurrence in future pregnancies. The objectives of this study were to determine the frequency of chromosome 22q11 deletions in patients with isolated CHD, and to compare between this prevalence among different groups of CHD. We studied a series of 75 children with CHD [proven by detailed echocardiography] attending the cardiology unit in El-Shatby pediatrics university hospital. After taking the parents consent, each patient was subjected to complete genetic assessment. Of 75 patients approached, 15 were found affected with well recognized genetic syndromes, and, therefore, excluded from the study. We analyzed the 60 patients with' apparently' isolated CHD for 22q11 microdeletions by PCR assay using three highly polymorphic microsatellite markers [D22S941, D22S944 and D22S264]. The results proved that VSD was the most common type of CHD. Cardiac phenotypes were classified into 2 groups conotruncal anomalies [5/60], and non- conotruncal anomalies [55/60]. Chromosome 22q11 deletions were identified only in three patients. The prevalence of 22q11 microdeletion in different groups of CHD was 20% [1/5] among the group of conotruncal anomalies, and 3.6% [2/55] among those with non-conotruncal anomalies. The 22q11 microdeletions are more prevalent among patients of the conotruncal group. There fore, it is recommended that patients with CHD of conotruncal type should undergo 22q11 microdeletion testing so genetic counseling can be offered as well as proper diagnosis management of associated manifestations