P0377 - Cardiac findings in patients with 1p36 gene deletion syndrome

Background/Purpose: Deletions in the 1p36 gene represent one of the most common deletion syndromes. Features include developmental delay, seizures, hearing and vision problems, feeding difficulties and anomalies affecting multiple organ systems. Cardiac findings include congenital heart defects and cardiomyopathy. Specifically, left ventricular noncompaction cardiomyopathy has been described in some patients with 1p36 gene deletion. Noncompaction cardiomyopathy is characterized by excessive, prominent trabeculations in the left ventricle and leads to arrhythmia, left ventricular dysfunction and emboli. We sought to outline cardiac findings in patients with diagnosed 1p36 gene deletion.

Methods: Retrospective chart review was performed on patients with known 1p36 gene deletion. Multiple factors were evaluated including frequency of follow-up with cardiology, hospitalizations, need for medication and findings on cardiac testing including echocardiography.

Results: Subjects with documented 1p36 gene deletion were identified who ranged in age from 3 to 19 years with 7 males and 8 females. Seven had regular follow-up with cardiology, six were seen intermittently and two were never evaluated. Nine subjects required hospitalization with three due to cardiac etiology. One patient suffered cardiac arrest with resultant death. Congenital heart defects were seen in 73% of subjects including atrial septal defect/patent foramen ovale (60%), patent ductus arteriosus (47%), ventricular septal defect (40%), aortic root dilation (20%) and coarctation of the aorta (6%). Surgical intervention was required in three subjects and catheter-based intervention in one subject. Of the five subjects with cardiomyopathy (33%), all had noncompaction cardiomyopathy with three being diagnosed in the first year of life and two later in life (7 and 14 years). The only subjects requiring cardiac medications were those with noncompaction cardiomyopathy. Average fractional shortening was depressed at 24.9 ± 8.17% and significantly worse (p = 0.02) as compared to the subjects without noncompaction (38.7 ± 7.53%). In addition, M-mode Z-scores for left ventricular end diastolic dimensions were significantly larger (p = 0.001) in the noncompaction subjects (2.21 ± 1.18) as compared to those without (-0.94 ± 0.98).

Conclusion: Our results demonstrate that cardiac manifestations are common in patients with 1p36 gene deletion syndrome. As previously described, many subjects demonstrate congenital heart defects. Our population demonstrated a higher instance of non-compaction cardiomyopathy as compared to prior reports in the literature. Furthermore, this subset of patients have significant clinical sequelae as evidenced by depressed systolic function and requirement for medication. Although three of these patients presented with noncompaction shortly after birth, two of our subjects presented later in life. This suggests that the need for regular follow-up with cardiology throughout childhood may be warranted for patients with 1p36 gene deletion. Additionally, future genetic research with regards to etiology of noncompaction cardiomyopathy may be directed at this noted association.