NHLBI Working Group
Cardiomyopathies in Children with Rare Diseases
The National Heart, Lung, and Blood Institute convened a Working Group
of investigators on March 14, 2005, in Bethesda, Maryland, to advise the
NHLBI and the NIH Office of Rare Diseases on new research directions needed
to understand the etiology of cardiomyopathies in children with rare diseases
and to improve the care of children with cardiomyopathies, particularly
those resulting from rare diseases.
The Working Group reviewed data on the etiology and underlying mechanisms
of various pediatric cardiomyopathies, the epidemiology of cardiomyopathies,
and current and potential treatments for these cardiomyopathies. The results
of the treatment of cardiomyopathies in children stand in stark contrast
to the successes seen with the treatment of adult cardiomyopathies. Moreover,
the diseases and associated consequences impose personal, medical, economic,
psychological, and social burdens on the children and their families.
Data indicate that survival of childhood cardiomyopathy patients in the
U.S. is bleak and does not substantially differ from that in other regions
of the world. Almost 40 percent of children with symptoms of cardiomyopathy
die or require cardiac transplantation, and this percentage has remained
substantially unaffected by medical research. Even though the search to
identify the genetic causes of structural heart disease began only ten
years ago, estimates to date indicate that perhaps more than 30 percent
of dilated cardiomyopathy is of genetic origin. Hypertrophic cardiomyopathy,
characterized by left ventricular hypertrophy, is an autosomal dominant
genetic disorder, the main pathological hallmarks of which are myocyte
hypertrophy and disarray, and interstitial fibrosis. It is a disease of
the cardiac sarcomere, and can result from mutations in cardiac ß-myosin
heavy chain, cardiac troponin T, cardiac troponin I, and myosin binding
protein C genes. Dilated cardiomyopathy, on the other hand, can result
from mutations in either sarcomeric or filamentous proteins. X-linked
forms of skeletal myopathy that affect young boys, such as Duchenne and
Becker muscular dystrophies, Barth's syndrome, and Danon's disease, exhibit
cardiac involvement in addition to other serious disease manifestations.
In a few instances, such as those involving deficiencies in metabolic
enzymes, specific treatments can reverse the cardiomyopathies, but this
is generally not the case for most cardiomyopathies associated with these
rare childhood diseases.
Although not all pediatric cardiomyopathies can be treated equally, commonalities
do exist. Developing technologies for detection and diagnosis that delineate
underlying genetic contributions could result in signatures for recognizing
specific diseases. Phenotypic characterization may make it possible to
begin clustering various cardiomyopathies for unified treatment approaches,
even though some types of these diseases will require individual approaches.
Understanding the molecular underpinnings of these diseases may make it
possible for targeted therapies to be developed.
The gaps in our knowledge, inability to screen and diagnose cardiomyopathies
in children, and inadequate treatments for children with cardiomyopathies
led to the following recommendations:
- Convene a group to define standards of care for managing pediatric
- Establish a Task Force to identify the research priorities and scientific
opportunities and barriers to address the public health problems associated
with pediatric cardiomyopathies.
- Develop new technologies and screening methods to delineate cardiac
gene mutations that result in pediatric cardiomyopathies.
- Develop new animal models for studying human genetic cardiomyopathies.
- Elucidate the mechanisms involved in viral myocardial disease.
- Establish an on-line health information system that could be accessed
by families and health professionals to obtain current peer-reviewed
information on pediatric cardiomyopathies, including screening/detection,
treatment, prevention, supportive care, and clinical trials.
- Initiate a clinical treatment trial of ACE inhibitors in Duchenne
muscular dystrophy patients asymptomatic for cardiac dysfunction.
- Stimulate research on enzyme replacement therapy in metabolic diseases
affecting the heart.
The Working Group is planning to publish a formal report, which will
include an overview of the field and review of the literature, as well
as the Group's recommendations. The report will be posted on the NHLBI
public web site with a link to the journal or journals where the report
is published. Anticipated publication date is 2006.
John Fakunding, Ph.D., NHLBI, NIH
Working Group Members
Chair: H. Lee Sweeney, Ph.D., University of Pennsylvania
- Linda Cripe, M.D., University of Cincinnati
- Anne M. Dubin, M.D., Stanford University Medical Center
- Patricia Furlong, Parent Project Muscular Dystrophy
- Steven E. Lipshultz, M.D., University of Miami School of Medicine
- Katherine McCurdy, Barth Syndrome Foundation, Inc.
- Elizabeth McNally, M.D., Ph.D., University of Chicago
- Antonio Perez-Atayde, M.D., Children's Hospital
- Christine Seidman, M.D., Brigham & Women's Hospital
- G. Michael Silberbach, M.D., Oregon Health Sciences University
- Arnold Strauss, M.D., Vanderbilt University Medical Center
- Jeffrey Towbin, M.D., Baylor College of Medicine
Last updated: April 30, 2005