Author + information
- Daniel P. Judge, MD⁎ (, )
- Nicole M. Johnson, ScM,
- Allison L. Cirino, MS and
- Carolyn Y. Ho, MD
- ↵⁎Johns Hopkins Hospital, Ross Building, Room 1049, 720 Rutland Avenue, Baltimore, Maryland 21205
We applaud the efforts by Drs. Donahue, Marchuk, and Rockman to review the current utility of genomics in heart failure (1). As they noted, this is a complex and developing field both in cardiology and in other medical specialties, with great potential to enhance our ability to diagnose and treat a variety of major cardiovascular disorders.
Although the primary focus of their study was not to review the utility of clinical genetic testing for familial cardiomyopathies, their strong negative statements need further clarification. In reference to familial cardiomyopathies, they state, “Given the current complexity of the field, no clinically useful genetic testing is available.” In their concluding paragraph, they note, “There is no current evidence supporting the routine clinical use of genomic information in the care of patients with cardiomyopathy.”
In the U.S. there are at least 9 clinical genetic laboratories performing lamin A/C (LMNA) sequencing for several conditions including familial dilated cardiomyopathy (FDC). As the researchers indicate, mutations in LMNAare associated with increased likelihood of arrhythmia, sudden death, and skeletal myopathy (2,3). Clinical testing for additional genes associated with FDC is also available. We believe that identifying a disease-causing mutation in LMNA, or other genes implicated in FDC, is important to determine which family members are at risk for developing disease and to allow initiation of treatment at an early, presymptomatic stage of disease.
In contrast to FDC, clinical genetic testing for hypertrophic cardiomyopathy has even greater likelihood of finding a responsible mutation (4). The Clinical Laboratory Improvement Amendments (CLIA)-approved Laboratory for Molecular Medicine at Harvard performs clinical genetic sequencing for eight sarcomere genes, as well as 2 additional genes for “unexplained hypertrophy.” When applied appropriately, 50% to 70% of cases will have a definite or probable disease-causing sarcomere mutation identified.
Clinical genetic testing for arrhythmogenic right ventricular cardiomyopathy (ARVC) has recently emerged owing to the prevalence of mutations in the plakophilin-2 gene, PKP2, among affected individuals (5). Improved recognition of the phenotypic correlations with mutations in this gene will lead to better understanding of the implications of a positive genetic test and assist in the often challenging diagnosis of ARVC (6,7).
Genetic testing is currently available for over a thousand conditions in the U.S., and its utility is interpreted in different contexts, including public health, clinical, personal, and social perspectives (8). Patients identify many reasons why they wish to proceed with genetic testing, including confirmation of a clinical diagnosis, presymptomatic identification of at-risk family members, and family planning. For many genetic disorders, techniques such as pre-implantation genetic diagnosis and sperm sorting (for X-linked conditions) are available. As direct-to-patient advertising for genetic testing expands to genetic cardiac diseases, a nihilistic approach to clinical genetic testing for inherited cardiomyopathy will leave behind physicians who still retain this philosophy (9).
We advocate genetic counseling for all patients with inherited cardiomyopathies, including discussion of the risks, benefits, limitations, and clinical implications of the possible outcomes of genetic testing. Only by embracing the appropriate use of clinical genetic testing will the cardiology community begin to benefit from advances that have been reached in other fields of medicine.
- American College of Cardiology Foundation
- Donahue M.P.,
- Marchuk D.A.,
- Rockman H.A.
- Dalal D.,
- Molin L.H.,
- Piccini J.P.,
- et al.
- Dalal D.,
- James C.,
- Devanagondi R.,
- et al.