title: 22q11.2 deletions in patients with conotruncal defects: data from 1,610 consecutive cases.
abstract: 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. 1,610 patients with conotruncal defects were sequentially tested for a 22q11del. The counts and frequencies of primary lesions and cardiac features were tabulated for those with and those without a 22q11del. Logistic regression models investigated cardiac features that predicted deletion status in tetralogy of Fallot (TOF). Deletion frequency varied by primary anatomic phenotype. Regardless of the cardiac diagnosis, a concurrent aortic arch anomaly (AAA) was strongly associated with deletion status [odds ratio (OR), 5.07; 95 % confidence interval (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, 5 % of the patients with an isolated conoventricular ventricular septal defect and normal aortic arch anatomy had a 22q11del, whereas no one with an interrupted aortic arch type A had a 22q11del. 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 to direct genetic screening for the 22q11.2 deletion syndrome in the cardiac patient.
authors.affiliation: Division of Pediatric Cardiology, The Children's Hospital of Philadelphia, Department of Pediatrics at the Perelman School of Medicine, The University of Pennsylvania, Philadelphia, PA, USA, peyvandis@email.chop.edu.
authors.forename: Shabnam
authors.initials: S
authors.lastname: Peyvandi
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Lupo
authors.forename: Jennifer
authors.initials: J
authors.lastname: Garbarini
authors.forename: Stacy
authors.initials: S
authors.lastname: Woyciechowski
authors.forename: Sharon
authors.initials: S
authors.lastname: Edman
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Emanuel
authors.forename: Laura E
authors.initials: LE
authors.lastname: Mitchell
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Goldmuntz
mesh_terms: D002892:Chromosomes, Human, Pair 22; D004062:DiGeorge Syndrome / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005838:Genotype; D006330:Heart Defects, Congenital / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010641:Phenotype; D015995:Prevalence; D011379:Prognosis; D012189:Retrospective Studies; D014481:United States / Q000453:epidemiology