Genetic Testing in Pediatric Left Ventricular Noncompaction

Abstract

Background: Left ventricular noncompaction (LVNC) can occur in isolation or can co-occur with a cardiomyopathy phenotype or cardiovascular malformation. The yield of cardiomyopathy gene panel testing in infants, children, and adolescents with a diagnosis of LVNC is unknown. By characterizing a pediatric population with LVNC, we sought to determine the yield of cardiomyopathy gene panel testing, distinguish the yield of testing for LVNC with or without co-occurring cardiac findings, and define additional factors influencing genetic testing yield.

Methods and results: One hundred twenty-eight individuals diagnosed with LVNC at ≤21 years of age were identified, including 59% with idiopathic pathogenesis, 32% with familial disease, and 9% with a syndromic or metabolic diagnosis. Overall, 75 individuals had either cardiomyopathy gene panel (n=65) or known variant testing (n=10). The yield of cardiomyopathy gene panel testing was 9%. The severity of LVNC by imaging criteria was not associated with positive genetic testing, co-occurring cardiac features, pathogenesis, family history, or myocardial dysfunction. Individuals with isolated LVNC were significantly less likely to have a positive genetic testing result compared with those with LVNC and co-occurring cardiomyopathy (0% versus 12%, respectively; P<0.01).

Conclusions: Genetic testing should be considered in individuals with cardiomyopathy co-occurring with LVNC. These data do not suggest an indication for cardiomyopathy gene panel testing in individuals with isolated LVNC in the absence of a family history of cardiomyopathy.

Keywords: cardiomyopathies; genetic testing; infant; pediatrics; phenotype.

Figure 1.

Imaging classifications in left ventricular noncompaction (LVNC). Echocardiographic images of an individual with a normal heart (A and D), an individual meeting standard imaging criteria for LVNC (B and E), and an individual meeting stringent imaging criteria for LVNC (C and F), as shown in the apical 4-chamber (A through C) and parasternal short-axis (D through F) views. The myocardium is excessively trabeculated with a thin compact layer in stringent cases, whereas the dimension of the noncompact layer and the degree of thinning of the compact layer varies in standard cases. In the example shown here, the standard case did not satisfy the ratio criteria (both the standard and stringent examples demonstrated blood flow between trabeculations by color Doppler, data not shown).

Figure 2.

Genetic testing and results by pathogenesis. The data included in cardiomyopathy (CM) gene panel yield calculation is shown with the number of cardiomyopathy gene panels indicated by dark gray (n=65) and the number of positive results in light gray (n=6). Within the syndromic group, many of the 12 individuals had multiple genetic tests. LVNC indicates left ventricular noncompaction; and VUS, variant of uncertain significance.