Changes In Aortic Root Size Over Time In Patients with 22Q11.2 Deletion Syndrome

Background:
Aortic root dilation (ARD) has been reported in patients with 22q11.2 deletion syndrome (22q11.2DS) with and without congenital heart defects (CHDs). The long-term implications of ARD in 22q11.2DS are unknown and thus the timing and necessity of long-term follow up is undefined. The aim of this study is to better understand the prevalence, longitudinal course and clinical risk factors for ARD in patients with 22q11.2DS without major CHDs.

Methods:
Patients less than 25 years with 22q11.2DS were identified from the electronic medical record and 22q and You Center database at the Children’s Hospital of Philadelphia. The subset from 1992-2018 with isolated aortic arch anomaly (AAA) or no intracardiac anomalies by echocardiogram were selected. Demographics including race, gender, height and weight at each echocardiogram were recorded. The aortic root was either measured on echocardiogram by a single observer or, for echocardiograms for which only the report was available, the measurement was abstracted from the report after inter-observer consistency was confirmed. Aortic root measurements were converted into the Pediatric Health Network Z-scores with an abnormal score set at ≥ 2.5. The probability of changing between normal aortic root size and ARD during follow-up was estimated. Mixed effects fractional polynomial models were used to identify contributing factors for ARD and the change in aortic root size over time.

Results:
Aortic root size at the level of the aortic sinuses was measured in 251 patients with 432 studies, of which 130 (52%) had isolated AAA; 108 patients had more than one study. 41 patients (16.3%) had ARD on at least one echocardiogram. The median age at the first echocardiogram was 4.79 years (min-max: 0-23.12) and the median Z-score was 1.20 (min-max: -2.20-5.40). Transition probability analysis showed that each year, 8.1% of patients who were normal developed ARD; 54.6% of patients with ARD continued to have ARD while 45.4% with ARD reverted to normal. The risk of ARD was significantly associated with male sex (per one year, OR=3.06, 95% CI=1.41-6.65; p=0.004), but not with age or presence of AAA. Z-score also decreased by age, and boys had a higher Z-score than girls (ß=0.72, SE=0.14, p< 0.001).

Conclusions:
ARD is observed in patients with 22q11.2DS without any other CHDs. During follow-up, a few patients with a normal aortic root converted to ARD. Those with ARD either continued to have dilation or reverted to normal. Male sex was associated with greater risk of ARD and aortic sinus Z-score decreased with age. There was no association between ARD and AAA. Without clear clinical correlates between aortic root size and complications in children or a predictable trajectory of ARD within 22q11.2DS, serial echocardiograms may only be warranted in those with significant ARD (Z-score>3) at diagnosis.