Affiliation:
1. Department of Clinical Genetics Erasmus Medical Center Rotterdam The Netherlands
2. Department of Cardiology Erasmus Medical Center Rotterdam The Netherlands
Abstract
Background
A genetic cause can be identified in 30% of noncompaction cardiomyopathy patients (
NCCM
) with clinical features ranging from asymptomatic cardiomyopathy to heart failure with major adverse cardiac events (
MACE
).
Methods and Results
To investigate genotype‐phenotype correlations, the genotypes and clinical features of genetic
NCCM
patients were collected from the literature. We compared age at diagnosis, cardiac features and risk for
MACE
according to mode of inheritance and molecular effects for defects in the most common sarcomere genes and
NCCM
subtypes. Geno‐ and phenotypes of 561
NCCM
patients from 172 studies showed increased risk in children for congenital heart defects (
P
<0.001) and
MACE
(
P
<0.001). In adult
NCCM
patients the main causes were single missense mutations in sarcomere genes. Children more frequently had an X‐linked or mitochondrial inherited defect (
P
=0.001) or chromosomal anomalies (
P
<0.001).
MYH
7
was involved in 48% of the sarcomere gene mutations.
MYH
7
and
ACTC
1
mutations had lower risk for
MACE
than
MYBPC
3
and
TTN
(
P
=0.001). The
NCCM
/dilated cardiomyopathy cardiac phenotype was the most frequent subtype (56%;
P
=0.022) and was associated with an increased risk for
MACE
and high risk for left ventricular systolic dysfunction (<0.001). In multivariate binary logistic regression analysis
MYBPC
3
,
TTN
,
arrhythmia ‐, non‐sarcomere non‐arrhythmia cardiomyopathy—and X‐linked genes were genetic predictors for
MACE
.
Conclusions
Sarcomere gene mutations were the most common cause in adult patients with lower risk of
MACE
. Children had multi‐systemic disorders with severe outcome, suggesting that the diagnostic and clinical approaches should be adjusted to age at presentation. The observed genotype‐phenotype correlations endorsed that
DNA
diagnostics for
NCCM
is important for clinical management and counseling of patients.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Cardiology and Cardiovascular Medicine
Cited by
62 articles.
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