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Dilated Cardiomyopathy Overview

, MD and , MS, LGC.

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Initial Posting: ; Last Update: September 24, 2015.


Clinical characteristics.

Nonsyndromic isolated dilated cardiomyopathy (DCM) is characterized by left ventricular enlargement and systolic dysfunction, a reduction in the myocardial force of contraction. DCM usually presents with any one of the following:

  • Heart failure with symptoms of congestion (edema, orthopnea, paroxysmal nocturnal dyspnea) and/or reduced cardiac output (fatigue, dyspnea on exertion)
  • Arrhythmias and/or conduction system disease
  • Thromboembolic disease (from left ventricular mural thrombus) including stroke


Genetic forms of DCM must be distinguished from other identifiable causes. After exclusion of all identifiable non-genetic causes in a proband, DCM is traditionally referred to as idiopathic dilated cardiomyopathy (IDC). When two or more closely related family members meet a formal diagnostic standard for IDC, the diagnosis of familial dilated cardiomyopathy (FDC) is made. Rare genetic variation has been primarily assessed and demonstrated in familial disease. Pathogenic variants have also been identified in simplex IDC cases, although the frequency of genetic causation in non-familial versus familial cases is not yet settled. The genetic forms of DCM are diagnosed by family history and molecular genetic testing.

Genetic counseling.

Genetic DCM can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Mitochondrial inheritance has also been reported; however, mitochondrial forms of DCM, although highly variable in presentation (including mild adult-onset forms), are usually syndromic and thus outside the scope of this review. Genetic counseling and risk assessment depend on determination of the specific DCM subtype in an individual.


Treatment of manifestations: Treatment by physicians skilled in diagnosis and management of symptomatic and asymptomatic DCM improves survival and quality of life. Treatment modalities include pharmacologic therapy, pacemakers, or implantable cardiac defibrillators; cardiac transplantation remains the definitive treatment for progressive DCM and advanced heart failure refractory to medical or device therapy.

Surveillance: Cardiovascular screening (physical examination, echocardiogram, ECG), is recommended:

  • Every one to three years when a known pathogenic variant has been identified in an asymptomatic individual, including children, especially if early onset has been noted in the family;
  • Every three to five years in adults or children who are first-degree relatives of an individual with idiopathic dilated cardiomyopathy in whom testing has not been performed or a pathogenic variant has not been identified.

Pregnancy management: Pregnancy is contraindicated in most women with DCM. Pregnant women with idiopathic or familial dilated cardiomyopathy should be followed by a high-risk obstetrician. Asymptomatic women with a family history of idiopathic dilated cardiomyopathy may be at risk for peripartum cardiomyopathy (PPCM) and pregnancy-associated cardiomyopathy (PACM) and warrant management as per guidelines for the evaluation of DCM.


Clinical Manifestations of Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) may be asymptomatic for a number of years. Presentation usually occurs late in the disease course with any one of the following:

  • Heart failure. Symptoms include those of congestion (edema, orthopnea, paroxysmal nocturnal dyspnea) and/or reduced cardiac output (fatigue, dyspnea on exertion).
  • Arrhythmias and/or conduction system disease. These commonly accompany advanced cardiomyopathy and heart failure. Some genetic causes (e.g., pathogenic variants in LMNA, SCN5A, DES) may have prominent conduction system disease or arrhythmias out of proportion to the degree of left ventricular dysfunction.
  • Thromboembolic disease. Stroke or systemic embolus, secondary to left ventricular mural thrombus, may also occur.

Onset usually occurs in adults in the fourth to sixth decade, although DCM may present in the fetal period, infancy, early or late childhood, adolescence, and in the elderly. Extensive additional background information is available [Burkett & Hershberger 2005, Sivasankaran et al 2005, Judge 2009, Dellefave & McNally 2010, Hershberger et al 2010a, Hershberger & Siegfried 2011].

Establishing the Diagnosis of Dilated Cardiomyopathy

The diagnosis of DCM is established by the presence of both of the following:

  • Left ventricular enlargement, most commonly assessed in adults by two-dimensional echocardiography, optimally assessed by a height- and gender-based approach [Vasan et al 1997]. Because of rapid growth in children expert cardiovascular assessment is recommended to assess left ventricular enlargement.
  • Systolic dysfunction, a reduction in the myocardial force of contraction
    • An ejection fraction of less than 50% is considered systolic dysfunction. The left ventricular ejection fraction is the most commonly used clinical measure of systolic dysfunction, and is usually estimated from a two-dimensional echocardiogram, from other noninvasive studies (e.g., cardiac nuclear or MRI studies), or from a left ventricular angiogram.
    • Fractional shortening is another clinical measure of systolic function. A fractional shortening of less than 25% is considered systolic dysfunction.

Establishing the Diagnosis of Idiopathic Dilated Cardiomyopathy

Idiopathic dilated cardiomyopathy (IDC) is a clinical diagnosis. After exclusion of all identifiable causes (except genetic), DCM is traditionally referred to as idiopathic dilated cardiomyopathy. It is important to note that because the term idiopathic dilated cardiomyopathy was used before evidence of genetic forms emerged, the diagnosis of IDC does not differentiate between genetic and non-genetic causes; therefore, a genetic etiology may be identified in a portion of individuals with ‘idiopathic dilated cardiomyopathy.’

The most common cause of DCM (in which the term DCM is used generically to describe the morphology and function of the left ventricle regardless of etiology) is ischemic injury, such as that caused by prior myocardial infarction from coronary artery disease.

After ischemic injury, other common causes of DCM include valvular and congenital heart disease, toxins (e.g., anthracyclines), thyroid disease, inflammatory conditions, myocarditis, severe long-standing hypertension, and radiation. Most of these can be detected with a careful medical history, a targeted physical examination, results of laboratory testing, an echocardiogram, and (if indicated) coronary angiography to exclude coronary artery disease.

Establishing the Diagnosis of Familial Dilated Cardiomyopathy (FDC)

When each of two or more closely related family members meet a formal diagnostic standard for idiopathic dilated cardiomyopathy (IDC) (i.e., all detectable causes of DCM, except genetic, have been ruled out), the diagnosis of familial dilated cardiomyopathy (FDC) is made [Burkett & Hershberger 2005].

FDC is largely an adult-onset disease, but has demonstrated a highly variable age of onset and reduced penetrance. These issues have been comprehensively reviewed [Burkett & Hershberger 2005, Sivasankaran et al 2005, Judge 2009, Dellefave & McNally 2010, Hershberger et al 2010a, Hershberger & Siegfried 2011].

Peripartum or pregnancy-associated cardiomyopathy (PPCM/PACM). Once considered distinct from DCM, PPCM and PACM (DCM occurring during or soon after pregnancy) are a part of the DCM clinical spectrum. Therefore, clinical and genetic testing recommendations for DCM (see Evaluation Strategy) apply for PPCM/PACM [Elkayam et al 2005, Morales et al 2010, van Spaendonck-Zwarts et al 2010].

Differential Diagnosis of DCM

Isolated DCM must be distinguished from other cardiomyopathies that may present with left ventricular involvement, including arrhythmogenic right ventricular cardiomyopathy (ARVC) with predominant LV involvement [Sen-Chowdhry et al 2008].

DCM must also be distinguished from syndromic forms; a selected list is provided [Hershberger et al 2009a, Hershberger et al 2013]. Of note, patients with syndromic DCM develop dilated cardiomyopathy and their management should include cardiovascular monitoring (see Management, Surveillance).

  • HFE-associated hereditary hemochromatosis. Hereditary hemochromatosis caused by biallelic pathogenic variants in HFE is an autosomal recessive disorder associated with cirrhosis, diabetes, hypermelanotic pigmentation, and increased serum iron and ferritin levels. Although iron overload from hemochromatosis can present as DCM, it more commonly presents as non-dilated and/or infiltrative cardiomyopathy.
  • Emery-Dreifuss muscular dystrophy is characterized by joint contractures, increased serum creatine kinase (CK) levels, arrhythmias, and childhood-onset muscle weakness. Mutation of LMNA has been shown to cause autosomal recessive and autosomal dominant forms. Mutation of EMD has been shown to cause an X-linked form.
  • Limb girdle muscular dystrophy 1B, one of the phenotypes included in the LGMD spectrum, is also caused by mutation of LMNA. LGMD1B is autosomal dominant and associated with mild joint contractures, increased CK levels, arrhythmias, and shoulder/hip-girdle weakness.
  • Laing distal myopathy primarily involves facial weakness and childhood-onset weakness of ankles, great toes, finger extensors, and neck flexors. This condition is inherited in autosomal dominant manner and caused by mutation of MYH7.
  • Carvajal syndrome (OMIM) is an autosomal recessive condition involving DCM with palmoplantar keratoderma and woolly hair. Mutation of DSP is causative.
  • Duchenne and Becker muscular dystrophy are X-linked disorders caused by mutation of DMD. In males, features most commonly involve muscle weakness and increased serum CK levels with loss of ambulation in childhood or later in life. Heterozygous females may present with isolated DCM.
  • Barth syndrome, an X-linked disorder caused by mutation of TAZ, involves growth retardation, lactic acidosis, neutropenia, and elevated levels of 3-methylglutaconic acid.
  • Mitochondrial DCM. Mitochondrial DNA pathogenic variants have been shown to cause a variety of complex phenotypes, including focal segmental glomerulosclerosis and Kearns-Sayre syndrome, among others.

Prevalence of DCM

The only formal estimate of idiopathic dilated cardiomyopathy (IDC) prevalence was a study conducted in Olmsted County, Minnesota from 1975 to 1984 that estimated IDC prevalence (as of 1-1-85) at 36.5:100,000 (~1:2,700) [Codd et al 1989]. This was twice the prevalence of hypertrophic cardiomyopathy (HCM), which was estimated at 19.7:100,000 (~1:5,000) from the same cohort during this study period.

Subsequently, multiple well-designed epidemiologic studies have shown an HCM prevalence of approximately 1:500. It is highly likely that the Olmsted County study also significantly underestimated the prevalence of IDC, as most experts consider IDC to be more common than HCM; however, no further formal population-based epidemiologic studies are available. A detailed rationale for revising the prevalence of DCM is provided with an estimate of 1:250 [Hershberger et al 2013].


Familial Dilated Cardiomyopathy (FDC)

Isolated (nonsyndromic) DCM of unknown cause (otherwise known as idiopathic dilated cardiomyopathy [IDC] in the cardiovascular literature) has been shown to have a genetic basis in some cases, although the frequency of the genetic basis of non-familial versus familial IDC is not yet settled.

Numerous large kindreds with FDC have provided the foundation for establishing genetic causation, and pathogenic variants in more than 30 genes are known to account for approximately 40%-50% of FDC [Hershberger & Siegfried 2011, Hershberger et al 2013] (Table 1). Simplex cases (i.e., a single occurrence of IDC in a family) have also been shown to host pathogenic variants [Hershberger et al 2008, Hershberger et al 2010b].

A range of approximately 10%-20% of DCM (with or without a positive family history) has been attributed to pathogenic truncating variants in TTN in from three DCM cohorts [Herman et al 2012]. Notably, however, up to 3% of reference populations have been shown to also carry truncating TTN variants.

Allelic heterogeneity is the rule; very few pathogenic variants have been seen in multiple families.

A few studies have provided evidence supporting a role for copy number variants (CNVs) in DCM, including a 4.8-kb deletion in EYA4 [Schönberger et al 2005], a large LMNA deletion found in one proband with familial disease [Gupta et al 2010], and a BAG3 whole-exon deletion in a large family [Norton et al 2011a]. Multiplex ligation probe amplification (MLPA) screening of LMNA in 58 probands failed to identify copy number variants [Norton et al 2011b]. In the absence of large studies, the prevalence of large genomic rearrangements in IDC or FDC remains unknown.

Regardless of whether a DCM-causing variant has been identified, evaluation of first-degree relatives of a proband with IDC by echocardiography and electrocardiography (ECG) has shown that approximately 20%-35% of probands will have familial disease [Michels et al 1992, Baig et al 1998, Grünig et al 1998].

Table 1.

Molecular Genetics of Familial Dilated Cardiomyopathy (FDC)

GeneProteinOMIM% of FDC Caused by Pathogenic Variants in This Gene 1Allelic Disorders 2
Autosomal dominant
TTN 3Titin18884010%-20%
  • LGMD2J 4
  • Myopathy, early-onset, w/fatal cardiomyopathy
  • Myopathy, proximal, w/early respiratory muscle involvement
  • Tibial muscular dystrophy, tardive
  • FHC 5
  • MYH7-related myosin storage myopathy
  • Left ventricular non-compaction
  • MYH7-related scapuloperoneal myopathy
SCN5ASodium channel protein type 5 subunit alpha6001632%-4%
MYBPC3Myosin-binding protein C, cardiac-type6009582%-4%
TNNT2Troponin T, cardiac muscle1910452.9%
  • Left ventricular non-compaction
  • TNNT2-related familial restrictive cardiomyopathy
BAG3BAG family molecular chaperone regulator 36038832.5%
ANKRD1Ankyrin repeat domain-containing protein 16095992.2%
RBM20RNA-binding protein 206131711.9%
TMPOLamina-associated polypeptide 2, isoform alpha1883801.1%
LDB3LIM domain-binding protein 36059061%
TPM1Tropomyosin alpha-1 chain191010<1%-1.9%
TNNI3Troponin I, cardiac muscle191044?1.3%
  • Restrictive cardiomyopathy
TNNC1Troponin C, slow skeletal and cardiac muscles191040<1%-1.3%
ACTC1Actin, alpha cardiac muscle 1102540<1%
CSRP3Cysteine and glycine-rich protein 3600824<1%
  • Delta sarcoglycanopathy (LGMD2F) 4
EYA4Eyes absent homolog 4603550?
PLNCardiac phospholamban172405?
  • Endocardial fibroelastosis type 2
  • Familial isolated non-compaction of the left ventricular myocardium
Autosomal recessive
TNNI3Troponin I, cardiac muscle191044<1%

Ordered by mode of inheritance and by frequency in descending order

See Dilated Cardiomyopathy: OMIM Phenotypic Series to view genes associated with this phenotype in OMIM.


The percentages provided (based on ≥2 reports screening large numbers of probands with IDC or FDC) should be interpreted as preliminary estimates.


Allelic disorders = other phenotypes caused by pathogenic variants in the same gene


Note that the role of mutation of TTN in DCM remains to be fully ascertained because pathogenic truncating variants were also identified in 3% of controls, making interpretation of results problematic. Truncating TTN variants found in individuals with DCM have been reported to cluster in the A-band region of the titin protein [Roberts et al 2015]. Some TTN pathogenic truncating variants have been observed not to segregate in all families with DCM [Norton et al 2013]. TTN missense variants may be benign; however, this type of variant has not been formally studied.


Simplex DCM

The frequency of genetic causation in persons with simplex dilated cardiomyopathy (i.e., a single occurrence in a family) has not been formally evaluated and remains largely unknown; however reports suggest a genetic basis with similar frequency in familial versus apparently simplex disease [Hershberger et al 2008, Hershberger et al 2010b].

Syndromic DCM

Numerous syndromes, many of which have genetic etiologies beyond those provided in Table 1, have been reported in association with DCM (see Differential Diagnosis). If any of the above features are present or if family history and/or physical examination suggest extra-cardiac disease, an evaluation by a clinical geneticist is recommended to rule out syndromic disease.

Evaluation Strategy to Identify or Confirm FDC

Guidelines for the genetic evaluation of dilated cardiomyopathy (DCM) when idiopathic dilated cardiomyopathy (IDC) has been established in a proband have been published [Hershberger et al 2009b].

Recommendations – outlined in this section – include a family history, cardiovascular evaluation of first-degree relatives, and molecular genetic testing.

This evaluation strategy aims to identify or confirm FDC and offer appropriate counseling and testing. This approach is particularly relevant because a person with DCM may remain asymptomatic for years.

Family History

A three- to four-generation family history (targeted to cardiovascular disease, including heart failure, DCM, cardiac transplantation, 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 FDC.

A diagnosis of FDC is made when two or more closely related family members have each met a rigorous diagnostic standard for IDC. With a diagnosis of FDC, family history information is evaluated to determine possible patterns of inheritance.

Both sides of the family should be considered as possibly contributing to familial disease. Families with FDC in both maternal and paternal lineages have been noted, and experience has shown that regardless of an apparent inheritance pattern in a family, assumptions regarding maternal or paternal inheritance of pathogenic variants in genes causing FDC in a given family may be unreliable and potentially misleading. A bilineal family has been reported, in which paternal and maternal lineages contribute an LMNA and a PLN pathogenic variant, respectively [Liu et al 2015].

Evaluation of First-Degree Relatives of a Proband for DCM

Current evidence indicates that idiopathic dilated cardiomyopathy (IDC) may be familial (and thus possibly genetic) in approximately 20%-35% of cases.

As a part of the evaluation of a proband to identify or confirm FDC, a cardiovascular evaluation of family members to detect any cardiovascular abnormality that would support the diagnosis of DCM is recommended. A cascade approach to cardiovascular evaluation should be used, i.e., proceeding with screening of first-degree relatives of newly identified persons with IDC in a family, including medical history, physical examination, echocardiogram, and ECG to determine if any is affected (including asymptomatic disease), thus supporting the diagnosis of FDC [Hershberger et al 2009b].

Because penetrance of DCM is age-dependent, repeat cardiovascular evaluations of at-risk first-degree relatives (to identify or confirm FDC) should be performed at intervals (see Management, Surveillance).

Note: If signs or symptoms of DCM are identified in any individuals evaluated as a part of these family studies, a full cardiovascular evaluation must be sought immediately (see Management).

Molecular Genetic Testing

Genetic testing may be offered to individuals with idiopathic dilated cardiomyopathy, familial dilated cardiomyopathy, peripartum cardiomyopathy (PPCM) or pregnancy associated cardiomyopathy (PACM).

While rare genetic variation has been primarily assessed and demonstrated in familial disease, the frequency of genetic causation in simplex DCM (i.e., a single occurrence in a family) remains formally untested in large research studies. Preliminary data, however, suggest similar pathogenic variant frequencies between familial and simplex cases [Hershberger et al 2010b]. Thus, molecular genetic testing in simplex cases should be considered. Some cardiovascular genetic medicine centers currently order genetic testing in such cases [Author, personal communication].

Single gene testing. Few genotype-phenotype correlations are known; however, testing of LMNA, SCN5A, and DES should be considered in those with conduction system disease or a family history of premature, unexpected sudden death [Hershberger et al 2009b, Ackerman et al 2011].

Multi-gene panel testing. Molecular genetic testing for multiple genes is now the usual course for cardiovascular genetic medicine; many genes have been combined into panels of several dozen per platform. Research reports suggest that 40%-50% or more of familial DCM has a genetic basis, suggesting similar detection rates for large multi-gene panels.

A healthcare provider ordering genetic testing using a multi-gene panel should:

  • Carefully review the clinical presentation and family history, as well as the genes included in the panel, as not all panels include the same genes. For example, not all laboratories evaluate mitochondrial genes, which may be more relevant overall for pediatric disease.
  • Be aware that genetic testing panels for DCM are continually updated; thus, repeat testing with a multi-gene panel may be indicated in an individual in whom prior testing with a smaller panel of genes did not identify a pathogenic variant.

Interpretation of genetic testing results – especially in simplex disease – may at present be challenging.

  • Because many variants appear to be private, and by definition, in simplex disease other affected family members will not be available for testing to assess segregation, it is likely that some pathogenic variants, otherwise meeting usual criteria for a category 2 variant [Richards et al 2008] [ACMG guidelines: “Sequence variation is previously unreported and is of the type which is expected to cause the disorder.”] will be of uncertain significance for DCM pathogenesis (variant of unknown significance [VUS]). Molecular genetic diagnostic laboratory reports vary on the interpretation of these types of variants, in part based on varying degrees of evidence of DCM causation in a specific gene with a category 2 variant. However, it is also possible that a previously identified and validated pathogenic variant may be identified in an individual with simplex disease.
  • Some probands are also known to harbor more than one rare, at least possibly disease-causing variant, further complicating the interpretation of genetic testing results [Hershberger et al 2008, Hershberger et al 2010b, Li et al 2010, Liu et al 2015].

Any healthcare provider ordering genetic testing must recognize and provide counseling for these outcomes [Burkett & Hershberger 2005, Judge 2009, Caleshu et al 2010, Hershberger et al 2010a, Hershberger & Siegfried 2011, Hershberger et al 2013]. Given the complexities, a referral to a cardiovascular genetics center should be considered. At such centers, board-certified genetic counselors are especially adept at comprehensively managing these issues, in concert with cardiologists who are expert in cardiovascular genetic and genomic medicine or MD geneticists.

Test characteristics. See Clinical Utility Gene Card [Posafalvi et al 2013] for information on test characteristics including sensitivity and specificity.

Genetic Counseling

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. —ED.

Mode of Inheritance

Familial dilated cardiomyopathy (FDC) may be inherited in an autosomal dominant, an autosomal recessive, or an X-linked manner. Most FDC (probably 80%-90%) appears to be autosomal dominant; X-linked and autosomal recessive forms are less common.

Autosomal recessive inheritance, most frequent in consanguineous families and persons with early-onset disease [Hanson & Hershberger 2001], can also result from pathogenic variants in genes commonly associated with autosomal dominant DCM.

Although mitochondrial inheritance has also been reported, these forms (which are highly variable in presentation, and include mild adult onset forms) are usually syndromic and thus outside the scope of this review.

Risk to Family Members — Autosomal Dominant Hereditary Dilated Cardiomyopathies

Parents of a proband

Note: (1) Although many individuals diagnosed with autosomal dominant IDC/FDC have an affected parent, the family history may appear to be negative because of failure to recognize the disorder in family members, early death of the parent before the onset of symptoms, or late onset of the disease in the affected parent. (2) If the parent is the individual in whom the pathogenic variant first occurred, it is possible that s/he may have somatic mosaicism for the pathogenic variant and may be mildly affected; somatic moasicism has not been reported to date.

Sibs of a proband

  • The risk to sibs depends on the genetic status of the proband's parents.
  • If a parent of the proband is affected and/or shown to have a pathogenic variant, the risk to the sibs of inheriting the pathogenic variant is 50%. Because of variable expression and reduced penetrance, no predictions can be made regarding age of onset or severity of disease.
  • For families in which both parents of a proband have a pathogenic variant, sibs have a 75% chance of inheriting one or two DCM-related pathogenic variants and a 25% chance of inheriting neither pathogenic variant.
  • If the parents have no signs of dilated cardiomyopathy, the risk to the sibs of a proband is still increased over the general population risk but cannot be precisely calculated. Recommendations for evaluation of sibs are outlined in Evaluation of First-Degree Relatives of a Proband for Dilated Cardiomyopathy.
  • If the pathogenic variant found in the proband cannot be detected in the leukocyte DNA of either parent, the risk to sibs of inheriting the pathogenic variant identified in the proband is low but not eliminated because of the possibility of parental germline mosaicism.
  • There are rare instances where the pathogenic variant found in the proband is not detected in either parent, but one or both parents have asymptomatic DCM by cardiovascular screening. In this case, the risk to sibs could be as high as 50% because of the possibility of a different pathogenic variant in the affected parent(s) that is not present in the proband.

Offspring of a proband. Each child of an individual with autosomal dominant DCM has at least a 50% chance of inheriting the parent's pathogenic variant. Because of variable expression and reduced penetrance, no predictions can be made regarding age of onset or severity of disease.

Risk to Family Members — Autosomal Recessive Hereditary Dilated Cardiomyopathies

Parents of a proband

  • The parents of an affected individual are obligate heterozygotes (i.e., carriers of one pathogenic variant).
  • Heterozygotes (carriers) are asymptomatic and are not at risk of developing the disorder.

Sibs of a proband

Offspring of a proband. Unless an individual with DCM has children with an affected individual or a carrier, his/her offspring will be obligate heterozygotes (carriers) for a pathogenic variant.

Carrier Detection

Carrier testing for at-risk relatives requires prior identification of the DCM-related pathogenic variants in the family.

Risk to Family Members — Nonsyndromic X-Linked DCM Caused by DMD or TAZ Pathogenic Variants

Parents of a proband

Sibs of a proband

  • The risk to sibs depends on the genetic status of the mother.
  • If the mother of the proband has a DMD or TAZ pathogenic variant, the chance of transmitting it in each pregnancy is 50%. Males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be heterozygotes and may or may not be affected.
  • If the proband represents a simplex case (i.e., a single occurrence in a family) and if the DMD or TAZ pathogenic variant cannot be detected in the leukocyte DNA of the mother, the risk to sibs is low but greater than that of the general population because of the possibility of maternal germline mosaicism.

Offspring of a proband. Affected males transmit the DMD or TAZ pathogenic variant to:

  • All of their daughters, who will be heterozygotes;
  • None of their sons.

Other family members of a proband. The proband's maternal aunts may be at risk of being heterozygous for the DMD or TAZ pathogenic variant and the aunt's offspring, depending on their gender, may be at risk of being heterozygous or being affected.

Heterozygote (Carrier) Detection

Molecular genetic testing of at-risk female relatives to determine their genetic status is most informative if the DMD or TAZ pathogenic variant has been identified in the proband.

Note: (1) Females who are heterozygous for a pathogenic variant and may be at some risk of developing disease. (2) Identification of female heterozygotes requires either (a) prior identification of the pathogenic variant in the family or, (b) if an affected male is not available for testing, molecular genetic testing first by sequence analysis, and if no pathogenic variant is identified, by gene-targeted deletion/duplication analysis.

Related Genetic Counseling Issues

See Evaluation of First-Degree Relatives of a Proband for Dilated Cardiomyopathy for information on testing at-risk relatives for the purpose of identifying or confirming the diagnosis of FDC in the family.

See Surveillance for recommendation for ongoing follow up of at-risk individuals for the purpose of early diagnosis of DCM and treatment.

Ambiguous echocardiographic and/or ECG results in asymptomatic at-risk relatives who do not meet criteria for DCM but nevertheless have abnormal cardiac findings (e.g., left ventricular enlargement with normal systolic function, decreased ejection fraction but normal-sized left ventricle, normal echocardiogram but significant conduction system disease and/or arrhythmias), with other causes ruled out, may represent early DCM. Such results complicate family risk assessment and management/surveillance for the individual and other family members.

Testing of at-risk asymptomatic adult relatives of individuals with DCM is possible after molecular genetic testing has identified the specific pathogenic variant in the family. Such testing should be performed in the context of formal genetic counseling and is not useful in predicting age of onset, severity, type of symptoms, or rate of progression in asymptomatic individuals. Testing of asymptomatic at-risk individuals with nonspecific or equivocal symptoms is predictive testing, not diagnostic testing.

Molecular genetic testing of asymptomatic individuals younger than age 18 years should be offered, as DCM onset can be highly variable even within families, in some cases occurring in infancy and childhood. Furthermore, families with predominant early-onset aggressive DCM have been reported.

Genetic testing facilitates identification of at-risk children who may benefit from early treatment, potentially forestalling the development of advanced disease. In families with early-onset aggressive DCM, identification of the familial pathogenic variant may guide more stringent clinical screening for asymptomatic but clinically detectable cardiovascular disease.

While concerns about negation of autonomy, genetic discrimination, stigmatization, and adverse family dynamics have been raised regarding testing of asymptomatic minors at risk for primarily adult-onset disorders, the benefit of early treatment is compelling enough to outweigh the potential risks.

For more information, see National Society of Genetic Counselors position statement on genetic testing of minors for adult-onset conditions and the American Academy of Pediatrics and American College of Medical Genetics and Genomics policy statement: ethical and policy issues in genetic testing and screening of children.

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, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.

Prenatal Testing and Preimplantation Genetic Diagnosis

Once the DCM-related pathogenic variant(s) have been identified in an affected family member, prenatal testing for a pregnancy at increased risk and preimplantation genetic diagnosis for DCM are possible.

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 regarding prenatal testing to be the choice of the parents, discussion of these issues is appropriate.


GeneReviews staff has selected the following disease-specific and/or umbrella support organizations and/or registries for the benefit of individuals with this disorder and their families. GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here.


Treatment of Manifestations

Treatment can favorably (and at times dramatically) affect the natural history of dilated cardiomyopathy (DCM). Management of DCM includes (1) pharmacologic therapy and (2) pacemaker and implantable cardiac defibrillator device therapy for symptomatic and asymptomatic disease. Care should be provided by physicians skilled in the diagnosis and treatment of patients with heart failure and DCM.

Symptoms include those related to heart failure, arrhythmia, or stroke. Symptomatic DCM represents late disease. Full medical therapy (ACE inhibitors, beta blockers) with evaluation for antiarrhythmic therapy (e.g., pacemakers, implantable cardiac defibrillators) should be considered by cardiovascular specialists with expertise in the field.

Individuals with idiopathic or familial dilated cardiomyopathy should:

  • Be counseled that idiopathic or familial dilated cardiomyopathy is treatable even prior to the onset of symptoms, that treatment may result in remission of DCM, and may forestall symptomatic disease; and that treatment of symptomatic disease (heart failure, arrhythmias, or thromboembolic disease) improves survival and quality of life;
  • Understand the symptoms of heart failure, arrhythmia (including presyncope and syncope), and thromboemoblic disease, and be counseled to urgently seek medical care with the new presentation of any of these symptoms.

Training of relatives and/or caregivers in cardiopulmonary resuscitation (CPR) should be suggested, particularly in families with a strong family history of sudden death and/or significant arrhythmias.

Cardiac transplantation remains the definitive treatment for progressive DCM and heart failure refractory to medical or device therapy.

Additional comprehensive guidelines are available [Yancy et al 2013].


An asymptomatic person with a known pathogenic variant. Cardiovascular screening (physical examination, echocardiogram, and ECG) should be performed every one to three years.

An asymptomatic at-risk first-degree relative in a kindred with an established diagnosis of FDC in which the family pathogenic variant is unknown. Depending on age, cardiovascular screening (physical examination, echocardiogram, and ECG) is indicated every three to five years. If an at-risk first-degree relative has evidence of idiopathic or familial dilated cardiomyopathy, the surveillance recommendations outlined here should extend to that person's first-degree relatives.

An asymptomatic first-degree relative of an individual with IDC in whom it is unknown if the IDC is familial should undergo cardiovascular screening (physical examination, echocardiogram, and ECG) every three to five years starting in childhood. If a first-degree at-risk relative shows evidence of dilated cardiomyopathy, a diagnosis of FDC is made and the surveillance recommendations outlined here should extend to that person's first-degree relatives.

For at-risk relatives with abnormal evaluation results that do not meet criteria for DCM but could be consistent with early DCM (e.g., left ventricular enlargement but normal systolic function, decreased ejection fraction but normal-sized left ventricle, normal echocardiogram with ECG abnormality) [Burkett & Hershberger 2005, Hershberger et al 2010a, Hershberger & Siegfried 2011], full cardiovascular assessment to evaluate for acquired causes of disease (e.g., coronary artery disease with history of myocardial infarction or history of exposure to cardiotoxic medications) and subsequent yearly screening are indicated.

Evaluation of Relatives at Risk

Using the strategy outlined in Evaluation of First-Degree Relatives of a Proband for Dilated Cardiomyopathy, it is appropriate to evaluate apparently asymptomatic older and younger relatives of an affected individual in order to identify as early as possible those who would benefit from surveillance and preventive measures.

When the pathogenic variant(s) are known, relatives may be offered genetic testing to help clarify risk. However, the absence of a likely pathogenic variant in an unaffected relative should be interpreted with caution, as it is possible that some families may have two or more pathogenic variants.

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

Pregnancy Management

In most cases, pregnancy is contraindicated in DCM.

Pregnant women with IDC or FDC should be followed by a high-risk obstetrician.

Asymptomatic women with a family history of idiopathic dilated cardiomyopathy may be at risk for peripartum cardiomyopathy (PPCM) and pregnancy-associated cardiomyopathy (PACM). Although PPCM and PACM have traditionally been thought to have an etiology separate from familial dilated cardiomyopathy, evidence supporting a genetic basis is emerging [Elkayam et al 2005, Morales et al 2010, van Spaendonck-Zwarts et al 2010]. Healthcare providers must, therefore, be aware of the possibility of an underlying genetic cause for PPCM/PACM and follow guidelines for the evaluation of DCM (see Evaluation Strategy). Reproductive genetic counseling and genetic testing should be considered in these cases.

Therapies Under Investigation

Search for access to information on clinical studies for a wide range of diseases and conditions. A clinical trial for symptomatic LMNA DCM is underway [Author, personal communication (2015)].


Published Guidelines/Consensus Statements

  • Committee on Bioethics, Committee on Genetics, and American College of Medical Genetics and Genomics Social, Ethical, Legal Issues Committee. Ethical and policy issues in genetic testing and screening of children. Available online. 2013. Accessed 1-23-17. [PubMed: 23428972]
  • National Society of Genetic Counselors. Position statement on genetic testing of minors for adult-onset disorders. Available online. 2017. Accessed 1-23-17.

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Chapter Notes

Author History

Ray E Hershberger, MD (2007-present)
Jessica D Kushner, MS, CGC; Oregon Health & Science University (2007-2013)
Ana Morales, MS, CGC (2013-present)
Sharie Parks, PhD; Oregon Health & Science University (2007-2013)

Revision History

  • 24 September 2015 (me) Comprehensive update posted live
  • 9 May 2013 (me) Comprehensive update posted live
  • 19 March 2009 (cd) Revision: sequence analysis and prenatal testing available clinically for TCAP, ABCC9, VCL, ACTN2, and CSRP3
  • 10 July 2008 (cd) Revision: clinical testing available for TTN mutations as a cause of dilated cardiomyopathy
  • 27 July 2007 (me) Review posted to live Web site
  • 6 December 2006 (jdk) Original submission
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