O0350 Oct.3: 5:19pm - Cardiac Evaluation Of Patients With 22Q11.2 Duplications

Background:
The 22q11.2 duplication syndrome (22q11.2DupS) has been diagnosed more frequently with the advent of microarray technology. Given that it disrupts the same region as the more familiar 22q11.2 deletion syndrome (22q11.2DS), patients with the duplication have been referred for similar organ system involvement but appear to display a distinct variable phenotype. To better describe the cardiac manifestations of the 22q11.2DupS, we performed a detailed review of a large 22q11.2DupS cohort in order to: (1) detail the cardiac phenotype, (2) estimate the prevalence of aortic arch anomalies, and (3) assess diagnoses made at outpatient cardiac evaluation following the genetic diagnosis of 22q11.2DupS if congenital heart disease (CHD) was not already identified.

Methods:
Records from 103 patients with 22q11.2DupS identified via the Cardiac Center and 22q and You Center databases at the Children’s Hospital of Philadelphia were reviewed to detail their cardiac and extracardiac phenotype. Particular note was taken of the aortic arch anatomy including sidedness and branching pattern. Extracardiac features were recorded using the genetics consultative note and other subspecialty notes when available.

Results:
Of 89 patients with 22q11.2DupS who underwent cardiac evaluations, 21.4% had CHD, with a wide range of cardiac phenotypes, most commonly including: isolated bicuspid aortic valve, hypoplastic left heart syndrome, and isolated ventricular septal defects (n=3 each), followed by tetralogy of Fallot, truncus arteriosus, and isolated atrial septal defects (n=2 each).
Seventy of the 89 patients had complete evaluations detailing aortic arch sidedness and branching pattern. Of these patients, 5 (7.2%) were found to have an aortic arch anomaly, all of whom had a concurrent intracardiac CHD. No patients had isolated aortic arch anomalies.
Of 46 patients who underwent outpatient cardiac consultation following diagnosis of 22q11.2DupS, 2 (4.4%) were found to have CHD. Both had isolated bicuspid aortic valve without stenosis.
The most common extracardiac manifestations of 22q11.2DupS were developmental (80.0%) or neurologic (58.8%), and 26.3% were described as having dysmorphic facies. Presence of CHD was associated with the presence of hepatic, renal, and skeletal abnormalities (p < 0.05).

Conclusions:
CHD is less common and phenotypically more diverse in patients with 22q11.2DupS compared to those with 22q11.2DS. Aortic arch anomalies are also less prevalent, and no patient in our cohort had an isolated aortic arch anomaly. Outpatient evaluation in patients with 22q11.2DupS without a previous diagnosis of CHD infrequently identified minor cardiac malformations. Certain types of extracardiac manifestations may be associated with CHD. Further study with larger numbers of patients will allow us to provide definitive guidance as to whether or not all patients with 22q11.2DupS require cardiac evaluation, or whether a subset may benefit.