CONDITION
Familial dilated cardiomyopathy (FDC)
CLINICAL BOTTOM LINE
• Dilated cardiomyopathy (DCM) is a broad category of conditions in which the heart muscle enlarges, causing left ventricular systolic dysfunction (ejection fraction [EF] <50%).
• Primary care practitioners should carry a high index of suspicion in cases of DCM for which no known acquired causes can be determined. Not all identified cases will demonstrate overt heart failure.
• Family history is vital, as familial dilated cardiomyopathy is diagnosed when at least 2 first- or second-degree family members meet the criteria for diagnosis of DCM after exclusion of acquired causes of DCM.1 A careful family history is also necessary to help distinguish FDC from idiopathic dilated cardiomyopathy (IDC), since variable expressivity and incomplete penetrance of genetic mutations can lead to a wide range of symptoms (Table 1).
• Genetic testing helps to identify the genes and mutations linked to FDC, which is especially helpful as more cases of FDC are being diagnosed that were formerly labeled idiopathic dilated cardiomyopathy. This knowledge helps to assist families in decision making and increases what is known about FDC.
• Diagnosis of FDC by family history and molecular genetic testing facilitates not only treatment of the patient's disease but also treatment of family members carrying the same genetic mutation prior to the onset of symptoms. Tailored genetic counseling and risk assessment can also be introduced. Once a diagnosis of FDC is established, family members should be urged to learn CPR.
WHAT IS FAMILIAL DILATED CARDIOMYOPATHY?
DCM is a broad range of conditions that cause the heart muscle to enlarge, resulting in left ventricular systolic dysfunction (EF <50%) that frequently leads to heart failure. Etiologies range from ischemic heart disease, the most common, to genetic mutations.
• Prevalence and epidemiology IDC causes approximately 25-33% of all cases of heart failure in the United States. Three recent studies have postulated that between 20-50% of cases of IDC may actually be FDC.2-4 DCM occurs more frequently in males than in females, with increased frequency in African Americans.5 Onset is generally in adulthood; however, the age of onset and presentation of symptoms vary greatly.
• Characteristics The presentation of DCM is widely variable. Patients can be asymptomatic or present with a number of symptoms. The most common are listed in Table 1.
DIFFERENTIAL DIAGNOSIS
• After acquired causes of dilated cardiomyopathy are ruled out, consider genetic testing based on the outcome of first-degree relative screening and possibly clinical presentation.
• In a patient with a diagnosis of IDC accompanied by significant conduction system disease and/or arrhythmias, molecular testing for LMNA-related cardiomyopathy (7-8% of all FDC) should be considered.6
• Screening with the other common mutations in the MYH7 gene (5-8% of FDC cases) may also be indicated.6
• Genetics referral is necessary.
DIAGNOSIS
• The diagnosis can be established through a variety of means, including
–Echocardiogram
• Determines left ventricular dilatation and systolic dysfunction (with left ventricular EF of <50%)
• Rules out congenital heart disease and/or valvulopathies as potential acquired causes of DCM
–ECG
• High degree of arrhythmogenicity exists in patients with DCM
–Chest radiograph
• Checks for cardiomegaly
• Determines the degree of pulmonary vascular congestion
–Laboratory testing to rule out acquired etiologies
• Bacterial and viral cultures, polymerase chain reaction detection of viral genomes, and antibody testing to test for infectious disease
• Serum ferritin level to assess for hemochromatosis
• CBC with differential to look for beta-thalassemia
• Brain natriuretic peptide levels to diagnose heart failure
–Nuclear medicine or thallium stress testing
• Results can rule out ischemic heart disease
–Family history (once acquired etiologies of DCM are ruled out)
–Should include detailed 3- to 4-generation family history exploring both maternal and paternal lineage that includes any sudden unexplained death, MI, stroke, or palpitations and/or arrhythmia.7 The American College of Cardiology/American Heart Association provides guidelines for the evaluation and treatment of heart failure (Table: ACC/AHA guidelines for obtaining a history to determine the cause of heart failure in the online version of this article).7
–Genetic testing
