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LMNA-Related Dilated Cardiomyopathy.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
2008 Jun 12 [updated 2016 Jul 7].

Author information

1
Professor of Medicine, Divisions of Human Genetics and Cardiovascular Medicine, The Ohio State University, Columbus, Ohio
2
Assistant Professor, Division of Human Genetics, The Ohio State University, Columbus, Ohio

Excerpt

CLINICAL CHARACTERISTICS:

LMNA-related dilated cardiomyopathy (DCM) is caused by pathogenic variants in LMNA and is characterized by left ventricular enlargement and/or reduced systolic function preceded or accompanied by significant conduction system disease and/or arrhythmias. LMNA-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:

LMNA sequence analysis identifies pathogenic variants in most individuals with LMNA-related DCM. Conduction system disease is detected by a 12-lead electrocardiogram (ECG); arrhythmias are detected by an ECG, 24-hour rhythm recording, or event monitor. Left ventricular enlargement is diagnosed with cardiac imaging; reduced systolic function is assessed by two-dimensional echocardiography, angiography, radioisotope scanning, or magnetic resonance imaging.

MANAGEMENT:

Treatment of manifestations: 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 cardiac defibrillator (ICD) and drug therapy as needed. Because risk for sudden cardiac death in LMNA-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/or anti-aldosterone agents. Progressive deterioration in left ventricular function is treated with an ICD, and some experts recommend anticoagulation. Cardiac transplantation or other advanced therapies may be considered for refractory disease in persons receiving comprehensive care from cardiovascular disease experts. Surveillance: Individuals with an LMNA pathogenic variant who are found to have any ECG abnormality should undergo a cardiovascular evaluation for disease progression at least annually. Asymptomatic individuals with a pathogenic LMNA variant should undergo cardiovascular evaluation (medical history, physical examination, echocardiogram, and ECG) every one to two years and/or whenever new symptoms arise. In families with a known LMNA pathogenic variant, at-risk individuals for whom genetic testing is not possible may be offered yearly cardiovascular screening. At onset of new symptoms an immediate evaluation for evidence of DCM and/or conduction system disease is indicated regardless of genetic status. Evaluation of relatives at risk: To facilitate prompt diagnosis, targeted LMNA genetic testing when the family-specific pathogenic variant is known; otherwise routine surveillance with cardiovascular screening tests. Pregnancy management: 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:

LMNA-related DCM is inherited in an autosomal dominant manner. Some individuals diagnosed with LMNA-related DCM have an affected parent; the proportion of cases caused by a de novo pathogenic variant is unknown. Each child of an individual with LMNA-related DCM has a 50% chance of inheriting the parent’s pathogenic variant. Prenatal diagnosis for LMNA-related DCM is technically possible when the pathogenic variant in the family is known.

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