How important are family and genetic follow-up and counseling in familial dilated cardiomyopathy?

Familial dilated cardiomyopathy (FDC) is a generally autosomal dominant genetic disease underlying a quarter to one half of cases of idiopathic dilated cardiomyopathy (1DC). It is defined as dilated cardiomyopathy in two or more closely related family members who otherwise meet the diagnostic criteria for IDC. The 1999 Guidelines for the study of familial dilated cardiomyopathies propose the following steps in the family study:

Evaluation of the proband’s relatives

Physical examination.

Standard electrocardiography.

Echocardiography (M-mode, 2-D, color flow).

Signal averaged electrocardiography (optional).

Blood sampling.

Evaluation of the affected relatives

Pedigree extension (study of the first-degree relatives of new affected family members).

Noninvasive examination and, when indicated, invasive examination (hemodynamic study, ventriculography, coronary angiography, endomyocardial biopsy).

Review of previous hospital records.

Genetic counseling.

Analysis of retrospective cases

Review of hospital records.

Interview of family physicians.

Interview of multiple informants among close relatives.


FDC may present with advanced heart failure or sudden cardiac death. A diagnosis of dilated cardiomyopathy is an indication for a thorough family history in at least the first- and second-degree relatives to exclude FDC. However, because the family history is much less sensitive than echocardiographic screening, and because FDC usually follows an autosomal dominant inheritance pattern, clinical screening of first-degree relatives (parents, siblings, children) by history, examination, electrocardiogram (ECG), and echocardiography is recommended.


Very little is known about the natural history of the familial disease. Both age of onset and clinical presentation can vary widely even within the same family. However, clinical outcome appears poorer in familial than in nonfamilial dilated cardiomyopathy, in particular in the juvenile phenotype. It is important to be able to study the early phase of the disease. For these reasons, long-term follow-up of affected and unaffected family members is critical. Unaffected, but at-risk, relatives should be rescreened every 3 to 5 years.

Left ventricular enlargement (LVE) may be a key indicator. Asymptomatic LVE may represent the earliest stage of FDC, with the disease genotype being carried by the family members with isolated LVE. A prospective follow-up of asymptomatic family members found that 27% of those with LVE developed FDC over 39 ± 14 months. Subjects with newly identified LVE in an FDC kindred warrant ongoing medical surveillance for symptomatic disease (examination, ECG, and echocardiography) every 1 to 3 years.

Conduction system disease is more difficult to assess, but left bundle branch block in an at-risk subject may be a harbinger of future disease and deserves close follow-up.

Genetic counseling

Family members diagnosed with FDC should be counseled that the disease course is unpredictable. It may be relatively benign and manageable on conventional therapy, or lead to progressive heart failure, requiring heart transplantation or resulting in sudden cardiac death. They should be informed that they have a heritable disease with a genetically transmissible risk to their offspring. Children of subjects with autoso-mal-dominant FDC have a 50% probability of inheriting the disease gene.

Those at genetic risk, but with no evidence of LVE, should be counseled about age-dependent penetrance and the possibility of future disease. They should be recommended to undergo regular screening, or screening if they ever have symptoms of cardiac dysfunction. For more detailed information on the clinical or genetic aspects of FDC, they should be referred to a cardiovascular expert in genetic cardiomyopathies, a genetic counselor, or geneticist.

Although we are learning more about the molecular genetics of dilated cardiomyopathy, molecular diagnoses are confined to a few X-linked, autosomal dominant, and matrilineal dilated cardiomyopathies, and extremely rare myopathies with heart involvement. Healthy carriers must be warned of the need for strict follow-up and/or treatment to prevent cardiac events and progressive disease. Once the molecular defect has been identified, elucidation of the relationship between gene defect, clinical features and prognosis, as observed in hypertrophic cardiomyopathy, could provide a solid platform for genetic counseling.

Arbustini E, Morbini P, Pilotto A, Gavazzi A, Tavazzi L. Familial dilated cardiomyopathy: from clinical presentation to molecular genetics. Eur Heart J. 2000;21:1825-1832.

Baig MK, Goldman JH, Caforio AL, Coonar AS, Keeling PJ, McKenna WJ. Familial dilated cardiomyopathy: cardiac abnormalities are common in asymptomatic relatives and may represent early disease. J Am Coll Cardiol. 1998;31:195-201.

Crispell KA, Hanson EL, Coates K, Toy W, Hershberger RE. Periodic rescreening is indicated for family members at risk of developing familial dilated cardiomyopathy. J Am Coll Cardiol. 2002;39:1503-1507.

Crispell KA, Wray A, Ni H, Nauman DJ, Hershberger RE. Clinical profiles of four large pedigrees with familial dilated cardiomyopathy: preliminary recommendations for clinical practice. J Am Coll Cardiol. 1999;34: 837-847.

Krajinovic M, Pinamonti B, Sinagra G, et al. Linkage of familial dilated cardiomyopathy to chromosome 9. Heart Muscle Disease Study Group. Am J Hum Genet. 1995;57:846-852.

Mestroni L, Maisch B, McKenna WJ, et al. Guidelines for the study of familial dilated cardiomyopathies. Collaborative Research Group of the European Human and Capital Mobility Project on Familial Dilated Cardiomyopathy. Eur Heart J. 1999,20:93-102.

Michels W, Moll PP, Miller FA, et al. The frequency of familial dilated cardiomyopathy in a series of patients with idiopathic dilated cardiomyopathy. N Engl J Med. 1992;326:77-82.


genetics; familial dilated cardiomyopathy; genetic counseling; screening

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