Abstract
Dilated cardiomyopathy (DCM) in infants and children can be partially explained by genetic cause but the catalogue of known genes is limited. We reviewed our database of 41 cases diagnosed with DCM before 18
years of age who underwent detailed clinical and genetic evaluation and have summarized here the evidence for mutations causing DCM in these cases from 15 genes (
PSEN1,
PSEN2, CSRP3,
LBD3,
MYH7, SCN5A, TCAP,
TNNT2,
LMNA,
MYBPC3,
MYH6, TNNC1,
TNNI3,
TPM1, and
RBM20). Thirty-five of the 41 pediatric cases had relatives with adult-onset DCM. More males (66%) were found among children diagnosed after 1
year of age with DCM. Nineteen mutations in 9 genes were identified among 15 out of 41 patients; 3 patients (diagnosed at ages 2
weeks, 9 and 13
years) had multiple mutations. Of the 19 mutations identified in 12 families, mutations in
TPM1 (32%) and
TNNT2 (21%) were the most commonly found. Of the 6 patients diagnosed before 1
year of age, 3 had mutations in
TPM1 (including a set of identical twins), 1 in
TNNT2, 1 in
MYH7, and 1 with multiple mutations (
MYH7 and
TNNC1). Most DCM was accompanied by advanced heart failure and need for cardiac transplantation. We conclude that in some cases, pediatric DCM has a genetic basis, which is complicated by allelic and locus heterogeneity as seen in adult-onset DCM. We suggest that future prospective comprehensive family-based genetic studies of pediatric DCM are indicated to further define mutation frequencies in known genes and to discover novel genetic cause.
