-Related Dilated Cardiomyopathy

CLINICAL CHARACTERISTICS

-related dilated cardiomyopathy (DCM) is characterized by left ventricular enlargement and/or reduced systolic function preceded (sometimes by many years) by or accompanied by conduction system disease and/or arrhythmias. -related DCM usually presents in early to mid-adulthood with symptomatic conduction system disease or arrhythmias, or with symptomatic DCM including heart failure or embolus from a left ventricular mural thrombus. Sudden cardiac death can occur, and in some instances is the presenting manifestation; sudden cardiac death may occur with minimal or no systolic dysfunction.

DIAGNOSIS/TESTING: The diagnosis of -related DCM is established in a proband with suggestive findings and a heterozygous pathogenic variant in identified by molecular genetic testing.

MANAGEMENT

Chronic atrial fibrillation is treated initially with attempts to restore normal sinus rhythm, anticoagulation, and rate control. Symptomatic supraventricular arrhythmias are usually treated with pharmacologic therapy or ablation; symptomatic bradyarrhythmias or significant heart block is treated with an electronic pacemaker. Symptomatic ventricular arrhythmias, ventricular tachycardia, ventricular fibrillation, and resuscitated sudden cardiac death are treated with an implantable cardioverter defibrillator (ICD) and drug therapy as needed. Because risk for sudden cardiac death in -related DCM accompanies heart block and bradyarrhythmias, ICD use (rather than just pacemaker use) has been recommended for all indications. Treatment of symptomatic DCM, including heart failure, is pharmacologic with ACE inhibitors, beta blockers, and other conventional approaches. Progressive deterioration in left ventricular function is treated with an ICD. Cardiac transplantation or other advanced therapies may be considered for refractory disease in persons receiving comprehensive care from cardiovascular disease experts. Individuals with an pathogenic variant who are found to have any EKG abnormality should undergo a cardiovascular evaluation for disease progression (EKG, 24-48 hour rhythm monitoring, LV function measurement) at least annually. Asymptomatic individuals with a pathogenic variant should undergo cardiovascular evaluation (medical history, physical examination, echocardiogram, and EKG) every one to two years and/or whenever new symptoms arise. In families with a known pathogenic variant, at-risk individuals for whom genetic testing is not possible should have yearly cardiovascular evaluation. At onset of new symptoms an immediate evaluation for evidence of DCM and/or conduction system disease is indicated regardless of genetic status. To facilitate prompt diagnosis, targeted genetic testing when the family-specific pathogenic variant is known; otherwise regular surveillance with cardiovascular screening tests. : Pregnancy is contraindicated in women with DCM. Pregnant women with DCM should be followed by a high-risk obstetrician. At-risk women with unknown genetic status should undergo a cardiovascular evaluation and be offered genetic counseling, ideally prior to pregnancy.

GENETIC COUNSELING

-related DCM is inherited in an autosomal dominant manner. Some individuals diagnosed with -related DCM have an affected parent; the proportion of individuals with -related DCM caused by a pathogenic variant is unknown. Each child of an individual with -related DCM has a 50% chance of inheriting the pathogenic variant. Once an pathogenic variant has been identified in an affected family member, prenatal testing and preimplantation genetic testing are possible.