Clinical Diagnosis

The diagnosis of LMNA-related dilated cardiomyopathy (DCM) is established in individuals with the following:

• A clinical diagnosis of DCM, usually in the setting of conduction system disease and/or supraventricular or ventricular arrhythmias

• An identified mutation in LMNA

The diagnosis of DCM is based on the principal findings of left ventricular enlargement and reduced systolic function in which other causes have been excluded:

• Reduced systolic function is usually described as a reduction in left ventricular ejection fraction, which can be measured by two-dimensional echocardiography, angiography, or nuclear left ventricular functional studies. An ejection fraction of less than 50% or a fractional shortening of less than 25%-30% is considered systolic dysfunction.

• Left ventricular enlargement is most commonly identified with two-dimensional echocardiography. Other testing modalities include cardiac computed tomography (CT), MRI, and left ventricular angiography or nuclear studies.

• Other causes to be excluded are, most importantly, coronary artery disease, structural heart disease (valvular heart disease, congenital heart disease, and others), thyroid disorders, and acute myocarditis.

Note: LMNA-related DCM is almost always associated with conduction system disease and/or arrhythmias that commonly occur prior to the development of heart failure symptoms. Clinicians should also be aware that in some cases the conduction system disease precedes any evidence of DCM (see Clinical Description).

Molecular Genetic Testing

Gene. LMNA is the only gene associated with LMNA-associated DCM.

Clinical testing

• Sequence analysis/ mutation scanning. For individuals known to have LMNA-related DCM, sequence analysis approaches a sensitivity of 100%, as almost all mutations identified to date have been missense, nonsense, or splice-site mutations.

• Duplication/deletion testing. Duplication/deletion testing may increase testing sensitivity, as two reports have identified LMNA-related DCM resulting from deletions [van Tintelen et al 2007, Gupta et al 2010].

Table 1. Summary of Molecular Genetic Testing Used in LMNA-Related Dilated Cardiomyopathy

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Gene Symbol	Test Method	Mutations Detected	Mutation Detection Frequency by Test Method 1	Test Availability
LMNA	Sequence analysis/ mutation scanning 2	Sequence variants 3	>99%	Clinical
	Duplication/ deletion testing 4	Exon(s) or whole-gene deletions/duplication	Unknown

Test Availability refers to availability in the GeneTests Laboratory Directory. GeneReviews designates a molecular genetic test as clinically available only if the test is listed in the GeneTests Laboratory Directory by either a US CLIA-licensed laboratory or a non-US clinical laboratory. GeneTests does not verify laboratory-submitted information or warrant any aspect of a laboratory's licensure or performance. Clinicians must communicate directly with the laboratories to verify information.

1. The ability of the test method used to detect a mutation that is present in the indicated gene

2. Sequence analysis and mutation scanning of the entire gene can have similar mutation detection frequencies; however, mutation detection rates for mutation scanning may vary considerably among laboratories depending on the specific protocol used.

3. Examples of mutations detected by sequence analysis may include small intragenic deletions/insertions and missense, nonsense, and splice site mutations.

4. Testing that identifies deletions/duplications not readily detectable by sequence analysis of genomic DNA; a variety of methods including quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), or targeted array GH (gene/segment-specific) may be used. A full array GH analysis that detects deletions/duplications across the genome may also include this gene/segment. See array GH.

Interpretation of test results. For issues to consider in interpretation of sequence analysis results, click here.

Testing Strategy

To confirm/establish the diagnosis of LMNA-related DCM in a proband. Molecular genetic testing for LMNA-related cardiomyopathy:

• Is indicated for all persons with DCM of unknown cause in the setting of prominent conduction system disease with or without supraventricular or ventricular arrhythmias;

• Should be considered for any person with DCM of unknown cause;

• May be appropriate in individuals with significant conduction system disease, which can precede evidence or accompany early evidence of DCM in some individuals.

Predictive testing for at-risk asymptomatic adult family members requires prior identification of the disease-causing mutation in the family.

Prenatal diagnosis for at-risk pregnancies requires prior identification of the disease-causing mutation in the family.

Note: It is the policy of GeneReviews to include clinical uses of testing available from laboratories listed in the GeneTests Laboratory Directory; inclusion does not necessarily reflect the endorsement of such uses by the author(s), editor(s), or reviewer(s).

Genetically Related (Allelic) Disorders

Mutations in LMNA cause several disorders of striated muscle, nerve, adipose, and vascular tissue, collectively referred to as the laminopathies. Laminopathies result primarily from missense mutations, with occasional nonsense and splice-site mutations and short insertions or deletions. A remarkable exception is the synonymous mutation (a nucleotide change that does not alter the amino acid) in LMNA codon 608 (GGC changed to GGT that does not change the Gly608 residue) causing Hutchinson-Gilford progeria. Synonymous mutations have also been suggested for limb-girdle muscular dystrophy type 1B [Todorova et al 2003].

• Muscular dystrophy

  • Autosomal dominant Emery-Dreifuss muscular dystrophy; a humero-peroneal muscular dystrophy, usually with adult onset. Cardiac conduction system disease is commonly observed.

  • Limb-girdle muscular dystrophy type 1B; dystrophy of the limb musculature, predominantly proximally. Cardiac conduction system disease is also commonly observed (see Limb-Girdle Muscular Dystrophy Overview).

• Neuropathy. Autosomal recessive Charcot-Marie-Tooth disease type 2B1 (CMT2B1; see Charcot-Marie-Tooth Neuropathy Type 2)

• Lipodystrophy. Autosomal dominant Dunnigan-type familial partial lipodystrophy (FPLD2), in which adipocytes degenerate during puberty, followed by abnormal fat deposition, glucose intolerance, and late-onset diabetes mellitus [Cao & Hegele 2000, Hegele et al 2000, Speckman et al 2000]. Most LMNA mutations causing FPLD2 involve arginine at amino acid residue 482.

• Hutchinson-Gilford Progeria syndrome. Synonymous autosomal dominant mutations in codon 608 cause an aberrant splicing of the terminal 50 amino acids of exon 11 [De Sandre-Giovannoli et al 2003, Eriksson et al 2003, Capell & Collins 2006].

• Other related disorders. See Emery-Dreifuss Muscular Dystrophy, Genetically Related Disorders.

Natural History

LMNA-related dilated cardiomyopathy (DCM) is characterized by left ventricular enlargement and reduced systolic function frequently accompanied by significant conduction system disease. LMNA-related DCM usually presents in adulthood either with conduction system disease commonly accompanied by arrhythmias or with symptomatic DCM, including heart failure or embolus from a left ventricular mural thrombus. However, LMNA-related DCM may be discovered in an asymptomatic person during a medical evaluation conducted for another reason (e.g., a routine preoperative ECG) or clinical screening of at-risk relatives.

Family studies suggest that conduction system disease commonly precedes the development of DCM by a few years to a decade or more. Conduction system involvement usually starts with disease of the sinus node and/or atrioventricular node that can manifest as sinus bradycardia, sinus node arrest with junctional rhythms, or heart block (commonly first-degree heart block that progresses to second- and third-degree block).

The following are also common:

• Symptomatic bradyarrhythmias requiring cardiac pacemakers

• Supraventricular arrhythmias including atrial flutter, atrial fibrillation, supraventricular tachycardia, and the sick sinus syndrome (i.e., tachycardia-bradycardia syndrome)

• Ventricular arrhythmias including frequent premature ventricular contractions (PVCs), ventricular tachycardia, and ventricular fibrillation

Sudden cardiac death may occur with progressive disease. Although more malignant, life-threatening arrhythmias may occur with longstanding and usually previously symptomatic DCM; sudden cardiac death can also be the presenting manifestation of LMNA-related DCM. Furthermore, only mild to moderate left ventricular dilatation despite progressive disease has been noted by some investigators.

Occasionally, individuals with LMNA-related cardiomyopathy also manifest signs or symptoms of skeletal myopathy, which may be associated with elevated serum creatine kinase (CK) concentration.

Large prospective longitudinal studies to define the range of natural history of individuals with LMNA mutations have not yet been published.

Genotype-Phenotype Correlations

No generalizable genotype-phenotype correlations have been established for LMNA-related DCM.

Penetrance

LMNA-related DCM demonstrates age-related penetrance with onset in the third and fourth decades, so that by the seventh decade penetrance is considered greater than 90%-95%.

Anticipation

Anticipation has not been observed.

Prevalence

Reliable estimates of the prevalence of DCM of unknown cause are not available.

The frequency of LMNA-related DCM in persons with DCM of unknown cause (otherwise known as idiopathic dilated cardiomyopathy [IDC]) ranges from 5% to 10% of familial DCM and 2% to 5% of non-familial DCM.

In the largest series to date, Parks et al [2008] analyzed 324 unrelated probands, of whom 187 had familial disease. Nineteen individuals (5.9% of all cases) had LMNA sequence variants, including 7.5% of probands with familial DCM and 3.6% of simplex cases.

Arbustini et al [2002] evaluated 73 probands with DCM and four families with atrioventricular block without DCM. Of the 15 of the 73 who had atrioventricular block, seven were familial cases and eight were simplex cases (i.e., a single occurrence in a family). Five of the seven familial cases had LMNA mutations. No LMNA mutations were identified in the eight simplex cases with DCM and atrioventricular block or in the four families with atrioventricular block without DCM.

Karkkainen et al [2006] identified six mutations in 66 probands with DCM who had survived heart transplantation in Finland (1986-1998).

Perrot et al [2009] identified LMNA mutations in five of 73 probands with DCM with conduction system disease.

Evaluations Following Initial Diagnosis

Following the diagnosis of LMNA-related dilated cardiomyopathy (DCM), if not previously completed, a three- to four-generation family history should be obtained, and the following evaluations performed:

• Comprehensive cardiovascular evaluation

  • Evaluation for conduction system disease and arrhythmia:

    • Personal and family history of presyncope, syncope, resuscitated sudden cardiac death, palpitations, and other symptoms of arrhythmia

    • Electrocardiography:
      
      Follow-up of abnormalities with additional testing as indicated (e.g., 24-hour monitoring or event monitors)
      
      Referral to a cardiologist or electrophysiologist for any indication of symptomatic disease
      
      Indicated in some patients: invasive electrophysiologic evaluation for conduction system disease

  • Evaluation for left ventricular dysfunction and DCM:

    • Family history for cardiomyopathy of any type, personal history of shortness of breath, dyspnea on exertion, paroxysmal nocturnal dyspnea, chest pain

    • Assessment of left ventricular function, most commonly by two-dimensional echocardiography to determine left ventricular dimensions and function. Alternatively, MRI provides similar data, and radionuclide ventriculography provides a measure of the ejection fraction.

    • If there is evidence of DCM, referral to a cardiovascular specialist for comprehensive cardiovascular evaluation for evidence of other causes of DCM (e.g., coronary artery disease)

• Measurement of serum CK concentration to evaluate for skeletal myopathy

• History and physical examination for signs and symptoms of skeletal myopathy. If there is evidence of myopathy, referral to a neuromuscular disease specialist for evaluation

Treatment of Manifestations

For the general approach to managing DCM, see Dilated Cardiomyopathy Overview, Management.

The Pasotti et al [2008] report (see Natural History) provides the most longitudinal data on LMNA-related DCM: 94 individuals with a LMNA mutation were followed for a median of 57 months (36-107 months). Additional reports of large prospective longitudinal natural history studies of LMNA-related DCM are not yet available.

In 2008 the Heart Failure Society of America commissioned a guideline document for the management of genetic cardiomyopathies that included specific mention of LMNA-related DCM [Hershberger et al 2009 (see ; registration or institutional access required)]. Elements of the guidelines include the following:

• Because of the complexity of treatment interventions in LMNA-related DCM in symptomatic and asymptomatic individuals, referral to centers with special expertise in cardiovascular genetic medicine should be considered.

• For evaluation of a person with newly diagnosed DCM, see Evaluations Following Initial Diagnosis.

• Consider genetic testing and genetic counseling.

• Consider therapy based on cardiac phenotype (i.e., DCM or arrhythmia).

• With an established arrhythmia or known risk of arrhythmia, consider ICD implantation before the ejection fraction falls below 35%. Note that this guideline was developed in large part because of the risk of lethal arrhythmias in persons with a LMNA mutation who have systolic function well above a left ventricular ejection fraction of 35%, the usual measure of systolic dysfunction below which ICDs are indicated in most US guidelines.

• Evaluate first-degree relatives, including extended family history, medical history, physical examination, echocardiogram, ECG.

The management of LMNA-related DCM is focused on treatment of conduction system disease, arrhythmia, and DCM.

Cardiac conduction system disease and arrhythmias

• Chronic atrial fibrillation unresponsive to cardioversion is treated with anticoagulants and agents for ventricular rate control.

• Other symptomatic supraventricular arrhythmias are treated with pharmacologic agents, and at times are augmented with electrophysiologic intervention (e.g., atrial or atrioventricular node ablations).

• Symptomatic bradyarrhythmias or asymptomatic but significant heart block is treated with an implantable electronic pacemaker. When a device is to be implanted, use of an implantable cardiac defibrillator (ICD) rather than an electronic pacemaker has been advocated and should be strongly considered, as the risk of mortality from sudden cardiac death usually accompanies supraventricular arrhythmias and conduction system disease. Sudden cardiac death presumably results from lethal tachyarrhythmias despite the presence of a pacemaker to treat bradyarrhythmias [van Berlo et al 2005, Meune et al 2006], and for this reason use of an ICD has been advocated for LMNA-related cardiomyopathy with significant conduction system disease and/or arrhythmia regardless of left ventricular ejection fraction [Hershberger et al 2009].

• Symptomatic ventricular arrhythmias, ventricular tachycardia, ventricular fibrillation, and resuscitated sudden cardiac death are treated with an ICD.

• When DCM is present and the left ventricular ejection fraction is less than 35%, an ICD should be implanted following the usual guidelines [Hunt 2005].

LMNA-related DCM

• Treatment of symptomatic DCM, including heart failure, is pharmacologic with ACE inhibitors and beta blockers, as summarized in guideline documents [Hunt et al 2005].

• With progressive deterioration in left ventricular function (left ventricular ejection fraction <30%), some experts recommend full anticoagulation to prevent the development of left ventricular mural thrombus and embolic events including stroke.

• Cardiac transplantation or other advanced therapies should be considered with progressive DCM, advancing heart failure, and otherwise refractory disease in persons receiving comprehensive cardiovascular care from experts in the field [Hunt 2005].

Surveillance

Screening and identification of DCM before the onset of symptoms enables the initiation of medical therapy that may delay disease progression.

• At-risk but clinically unaffected first-degree relatives are advised to undergo cardiovascular screening tests (medical history, physical examination, echocardiogram, and ECG) every two to five years and/or whenever new symptoms present [Burkett & Hershberger 2005, Hershberger et al 2009].

• Asymptomatic relatives who have the family-specific LMNA mutation are advised to undergo cardiovascular screening tests (medical history, physical examination, echocardiogram, and ECG) every one to two years and/or whenever new symptoms present [Burkett & Hershberger 2005, Hershberger et al 2009].

Testing of Relatives at Risk

When the disease-causing LMNA mutation has been identified in a family, molecular genetic testing can be offered to relatives at risk in order to facilitate prompt diagnosis, surveillance, and treatment in those in whom the disease-causing LMNA mutation has been detected.

If molecular genetic testing is not available, the first-degree relatives of a proband with LMNA-related DCM should be evaluated by medical history, physical examination, echocardiogram, and ECG to determine if any have detectable DCM and/or conduction system disease.

Note: Because the age of onset is variable and penetrance is reduced, a normal baseline echocardiogram and ECG in a first-degree relative who has not undergone molecular genetic testing does not rule out LMNA-related DCM in that individual, and the recommendations set forth in Surveillance should be followed.

Any abnormal cardiovascular test results in a relative of a proband should be followed up with a full cardiovascular assessment to evaluate for any acquired causes of disease (e.g., coronary artery disease). Results on screening tests that do not meet criteria for DCM but do show some abnormality (e.g., left ventricular enlargement but normal function; decreased ejection fraction but normal-sized left ventricle) may reflect variable expression of LMNA-related DCM in that relative. Close surveillance (e.g., cardiovascular testing every 1-2 years) for progression of cardiovascular disease is recommended for such individuals.

Note: Because most LMNA-related DCM is adult onset, clinical screening is usually not recommended for children or adolescents unless onset of disease in the proband was in these age groups, or unless cardiovascular symptoms are present.

See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes.

Therapies Under Investigation

Search ClinicalTrials.gov for access to information on clinical studies for a wide range of diseases and conditions. Note: There may not be clinical trials for this disorder.

Other

Genetics clinics, staffed by genetics professionals, provide information for individuals and families regarding the natural history, treatment, mode of inheritance, and genetic risks to other family members as well as information about available consumer-oriented resources. See the GeneTests Clinic Directory.

See Consumer Resources for disease-specific and/or umbrella support organizations for this disorder. These organizations have been established for individuals and families to provide information, support, and contact with other affected individuals.

Mode of Inheritance

LMNA-related dilated cardiomyopathy (DCM) is inherited in an autosomal dominant manner.

Risk to Family Members

Parents of a proband

• Some individuals diagnosed with LMNA-related DCM have an affected parent.

• A proband with LMNA-related DCM may have the disorder as the result of a new gene mutation. The proportion of cases caused by de novo mutations is unknown.

• Recommendations for the evaluation of parents of a proband with an apparent de novo mutation include review of medical history, physical examination, echocardiogram, ECG to determine if a parent has detectable DCM and/or conduction system disease, and molecular genetic testing if the mutation has been identified in the proband. Evaluation of parents may determine that one is affected but has previously escaped diagnosis and/or has a milder phenotypic presentation, including evidence of DCM on echocardiogram without clinical heart failure symptoms (i.e., asymptomatic affected).

Note: (1) Although some individuals diagnosed with LMNA-related DCM have an affected parent, the family history may appear to be negative because of early death of the parent before the onset of symptoms, late onset of the disease in the affected parent, or non-penetrance of the LMNA mutation. (2) If the parent is the individual in whom the mutation first occurred, s/he may have somatic mosaicism for the mutation and may be mildly/minimally affected, although this has not yet been reported.

Sibs of a proband

• The risk to the sibs of the proband depends on the genetic status of the proband’s parents.

• If one parent of the proband is affected, the risk to the sibs is 50%. However, because of variable expression and reduced penetrance, no predictions can be made regarding age of onset, severity, or course of disease.

• When neither parent has signs of LMNA-related DCM, the risk to the sibs of a proband is increased over the general population risk, but cannot be precisely calculated. Genetic testing may help to clarify risk. Recommendations for evaluation of sibs are included in Testing of Relatives at Risk.

• If the disease-causing mutation found in the proband cannot be detected in the DNA of either parent, the risk to sibs is low but greater than that of the general population because of the possibility of germline mosaicism, although this has not yet been reported.

• When the family-specific mutation is known, the sibs may be offered genetic testing to help clarify risk. However, the absence of a likely disease-causing mutation in an unaffected sib should be interpreted with caution, as it is possible that in some families with DCM more than one etiology may be causative. See discussion of Parks et al [2008] in Natural History.

Offspring of a proband. Each child of an individual with LMNA-related DCM has a 50% chance of inheriting the parent’s mutation. However, because of variable expression and reduced penetrance, no predictions can be made regarding age of onset, severity, or course of disease.

Other family members of a proband. The risk to other family members depends on the status of the proband's parents. If a parent is affected or has an LMNA mutation despite being clinically asymptomatic, his or her family members may be at risk.

Related Genetic Counseling Issues

See Management, Testing of Relatives at Risk for information on testing at-risk relatives for the purpose of early diagnosis and treatment.

Family history. A detailed three- to four-generation family history (including heart failure, DCM, cardiac transplantation, pacemakers or implantable cardiac defibrillators, unexplained sudden death, unexplained cardiac conduction system disease and/or arrhythmia, or unexplained stroke or other thromboembolic disease) should be obtained from relatives to assess the possibility of familial disease. Conduction system disease, particularly with pacemakers, is particularly suggestive of LMNA-related DCM.

Both sides of the family should be considered as possibly contributing. Families with dilated cardiomyopathy in both maternal and paternal lineages have been described [Crispell et al 1999, Parks et al 2008], and experience has shown that regardless of an apparent inheritance pattern in a family, assumptions regarding maternal or paternal inheritance of mutations in genes causing familial dilated cardiomyopathy in a given family may be unreliable and potentially misleading. See discussion of Parks et al [2008] in Natural History.

Molecular genetic testing of at-risk asymptomatic adult relatives of individuals with LMNA-related DCM is possible if molecular genetic testing has identified the specific mutation in an affected relative. Such testing should only be performed in the context of formal genetic counseling, and is not useful in predicting age of disease onset, severity, or rate of progression. Testing of asymptomatic at-risk individuals is considered predictive testing for predisposition to LMNA-related DCM, not diagnostic testing.

Molecular genetic testing of asymptomatic individuals younger than age 18 years who are at risk for adult-onset disorders for which no treatment exists is not considered appropriate, primarily because it negates the autonomy of the child with no compelling benefit. Further, concern exists regarding the potential adverse effects that such information may have on family dynamics, the risk of discrimination and stigmatization in the future, and the anxiety that such information may cause.

However, early clinical or molecular genetic diagnosis of DCM may offer a benefit that outweighs the arguments against testing asymptomatic minors. Early treatment may forestall development of more advanced disease, including slowing progression to advanced heart failure or the prevention of sudden cardiac death, and thus justify screening and genetic testing of asymptomatic minors in families demonstrating early-onset and/or aggressive disease. In these cases, knowledge that a child has inherited an LMNA mutation may help guide more stringent clinical screening for asymptomatic but clinically detectable cardiovascular disease.

Genetic testing is always indicated in affected or symptomatic individuals in a family with established LMNA-related DCM, regardless of age.

See also the National Society of Genetic Counselors resolution on genetic testing of children and the American Society of Human Genetics and American College of Medical Genetics points to consider: ethical, legal, and psychosocial implications of genetic testing in children and adolescents.

Family planning

• The optimal time for determination of genetic risk and discussion of the availability of prenatal testing is before pregnancy. Similarly, decisions about testing to determine the genetic status of at-risk asymptomatic family members are best made before pregnancy.

• It is appropriate to offer genetic counseling (including discussion of potential risks to offspring and reproductive options) to young adults who are affected or at risk.

DNA banking is the storage of DNA (typically extracted from white blood cells) for possible future use. Because it is likely that testing methodology and our understanding of genes, mutations, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals. See for a list of laboratories offering DNA banking.

Prenatal Testing

Prenatal diagnosis for LMNA-related DCM is technically possible by analyzing fetal DNA extracted from cells obtained by chorionic villus sampling (CVS) at approximately ten to 12 weeks' gestation or from cells obtained through amniocentesis at approximately 15 to 18 weeks' gestation. The disease-causing mutation of an affected family member must be identified before prenatal testing can be performed.

Note: Gestational age is expressed as menstrual weeks calculated either from the first day of the last normal menstrual period or by ultrasound measurements.

Laboratories offering molecular genetic testing for prenatal diagnosis of LMNA-related DCM are listed in the GeneTests Laboratory Directory.

Requests for prenatal testing for (typically) adult-onset diseases are not common. Differences in perspective exist among medical professionals and within families regarding the use of prenatal testing, particularly if the testing is being considered for the purpose of pregnancy termination rather than early diagnosis. Although most centers would consider decisions about prenatal testing to be the choice of the parents, discussion of these issues is appropriate.

Preimplantation genetic diagnosis (PGD) may be available for families in which the disease-causing mutation has been identified. For laboratories offering PGD, see .

Note: It is the policy of GeneReviews to include clinical uses of testing available from laboratories listed in the GeneTests Laboratory Directory; inclusion does not necessarily reflect the endorsement of such uses by the author(s), editor(s), or reviewer(s).

Published Guidelines/Consensus Statements

1. Hershberger RE, Lindenfeld J, Mestroni L, Seidman CE, Taylor MR, Towbin JA; Heart Failure Society of America. Genetic evaluation of cardiomyopathy--a Heart Failure Society of America practice guideline. 2009. Available online (registration or institutional access required). Accessed 4-1-11.

Literature Cited

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Suggested Reading

1. Hershberger RE. Cardiovascular genetic medicine: evolving concepts, rationale, and implementation. J Cardiovasc Transl Res. 2008;1:137–43. [PubMed: 20559908]
2. Sylvius N, Tesson F. Lamin A/C and cardiac diseases. Curr Opin Cardiol. 2006;21:159–65. [PubMed: 16601451]

Author Notes

Web site: Familial Dilated Cardiomyopathy Research Project

Author History

Jason Cowan, MS; University of Miami Miller School of Medicine (2008-2011)
Ray E Hershberger, MD (2008-present)
Ana Morales, MS, CGC; University of Miami Miller School of Medicine (2008-2011)

Revision History

• 5 April 2011 (me) Comprehensive update posted live

• 12 June 2008 (me) Review posted live

• 7 January 2008 (rh) Original submission