Diastolic dysfunction without left ventricular hypertrophy is an early finding in children with hypertrophic cardiomyopathy-causing mutations in the beta-myosin heavy chain, alpha-tropomyosin, and myosin-binding protein C genes.
OBJECTIVE
We investigated the presence of left ventricular hypertrophy (LVH) and features of diastolic dysfunction in genotype-confirmed children from families with hypertrophic cardiomyopathy (HCM) and healthy control children.


BACKGROUND
In subjects with HCM-causing mutations, LVH usually does not evolve until adolescence. Diastolic dysfunction has not been systematically evaluated in children carrying HCM-causing mutations.


METHODS
All children (aged 1.5-16.7 years) from 14 HCM families with identified disease-causing mutations (the Arg719Trp mutation in the beta-myosin heavy chain gene [MYH7], the Asp175Asn mutation in the alpha-tropomyosin gene [TPM1], the Gln1061X mutation in the myosin-binding protein C gene [MYBPC3], and the IVS5-2A-->C mutation in the MYBPC3 gene) and 53 matched control children were examined with electrocardiography and 2- and 3-dimensional echocardiography (2DE and 3DE). Natriuretic peptides were measured in children from HCM families and 67 control children.


RESULTS
Of 53 children from HCM families, 27 (51%) had a disease-causing mutation (G+). G+ children had slightly thicker septum on 2DE compared with the control children (P = .004), but only 3 (11%) of 27 G+ children exceeded the 95th percentile values of the body surface area-adjusted maximal LV thickness of healthy children (the major echocardiographic criterion for HCM). However, prolonged isovolumetric relaxation time, increased left atrial volume on 3DE, or increased levels of NT-proANP, all features suggestive of diastolic dysfunction, were found in 14 (52%) of 27 G+ children.


CONCLUSIONS
In children with HCM-causing mutations, signs of diastolic dysfunction are found in about half of the cases, as LVH is present only in small percentage of these children.
Poutanen
Tuija
T
Department of Pediatrics, Kuopio University Hospital, Kuopio, Finland. tuija.poutanen@koti.tpo.fi
Tikanoja
Tero
T
Jääskeläinen
Pertti
P
Jokinen
Eero
E
Silvast
Annuli
A
Laakso
Markku
M
Kuusisto
Johanna
J
D000293:Adolescent; D009320:Atrial Natriuretic Factor / Q000097:blood; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics* / Q000503:physiopathology*; D002352:Carrier Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D003971:Diastole / Q000235:genetics*; D015150:Echocardiography, Doppler; D004562:Electrocardiography; D005260:Female; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000235:genetics*; D021621:Imaging, Three-Dimensional; D007223:Infant; D008297:Male; D014335:Tropomyosin / Q000235:genetics*; D024723:Ventricular Myosins / Q000235:genetics*; D000099163:Myosin Binding Protein C
D009320:Atrial Natriuretic Factor; D002352:Carrier Proteins; D014335:Tropomyosin; D024723:Ventricular Myosins; D000099163:Myosin Binding Protein C; C490775:TPM1 protein, human