22q11.2 Deletions in Patients with Conotruncal Defects: Data from 1,610 Consecutive Cases

Abstract

Background The 22q11.2 deletion syndrome is characterized by multiple congenital anomalies including conotruncal cardiac defects. Identifying the patient with a 22q11.2 deletion (22q11del) can be challenging because many extracardiac features become apparent later in life. We sought to better define the cardiac phenotype associated with a 22q11del to help direct genetic testing. Methods 1,610 patients with conotruncal defects were sequentially tested for a 22q11del. Counts and frequencies for primary lesions and cardiac features were tabulated for those with and without a 22q11del. Logistic regression models investigated cardiac features that predicted deletion status in tetralogy of Fallot (TOF). Results Deletion frequency varied by primary anatomic phenotype. Regardless of the cardiac diagnosis, a concurrent aortic arch anomaly (AAA) was strongly associated with deletion status (OR 5.07, 95% CI: 3.66–7.04). In the TOF subset, the strongest predictor of deletion status was an AAA (OR 3.14, 95% CI: 1.87–5.27, p <0.001), followed by pulmonary valve atresia (OR 2.03, 95% CI: 1.02–4.02, p= 0.04). Among those with double outlet right ventricle and transposition of the great arteries, only those with an AAA had a 22q11del. However, five percent of patients with an isolated conoventricular ventricular septal defect and normal aortic arch anatomy had a 22q11del, while no one with an IAA-A had a 22q11del. Conclusion A subset of patients with conotruncal defects are at risk for a 22q11del. A concurrent AAA increases the risk regardless of the intracardiac anatomy. These findings help direct genetic screening for the 22q11.2 deletion syndrome in the cardiac patient.

Pattern of Congenital Heart Defects in 22q11 Microdeletion Syndrome in India – A Tertiary Care Cardiac Hospital Based Study

“…5,[11][12][13] The present study found 82.29% of the cohort with conotruncal defects. This appears to be a common phenomenon in various studies across the world in different geographic zones.…”

“…3,4,8,9 In other studies, children with selected cardiac diagnosis were screened for 22q11.2 microdeletion to identify the relative frequency. 5,[10][11][12][13] In the present study cardiac diagnosis of all the children with positive for 22q11.2 microdeletion were studied in detail using available data on retrospective basis.…”

“…Similar pattern is described by other two studies by Ryan et al and Park et al 3,4 Prevalence of 22q11.2 microdeletion among conotruncal heart defects range form 13-48%. 5,12,14 Conotruncal defects associated with aortic arch anomalies, aberrant subclavian artery and anomalies of pulmonary artery and pulmonary blood supply, abnormal infundibular septum and abnormal semilunar valves are more likely to be diagnosed with 22q11.2 microdeletion syndrome. 13,14 Incidence of these vascular aberrations in the present study was seen in higher association among conotruncal anomalies.…”

“…1,3,4 Main diagnostic clues to 22q11.2 microdeletion syndrome could be typical Congenital Heart Defects (conotruncal anomalies or aortic arch anomalies), characteristic phenotypic features and other extracardiac manifestations like hypocalcemia. 3,4,5 However clinical features of 22q11.2 microdeletion syndrome are highly variable. Few children might have variable or subtle phenotypic features and might not have typical Congenital Heart Defects.…”

22q11.2 Deletion Syndrome: Symptoms, Diagnosis, Treatment

“…Наиболее частыми проявлениями синдрома 22q11DS являются конотрункальные пороки сердца, которые составляют до 50% всех врожденных пороков серд-ца у новорожденных [29,30]. Конотрункальные пороки относятся к критическим врожденным порокам сердца Обзор литературы периода новорожденности, т. е. таким порокам, при кото-рых большинство пациентов умирают в течение первого года жизни.…”