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Emery-Dreifuss Muscular Dystrophy.

Source

GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
2004 Sep 29 [updated 2015 Nov 25].

Author information

1
Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS_974, CNRS FRE 3617, Centre de Recherche en Myologie, Paris, France
2
AP-HP, Laboratoire de Biochimie & Génétique Moléculaire, Hôpital Cochin, Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS_974, CNRS FRE 3617, Centre de Recherche en Myologie, Paris, France
3
Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS_974, CNRS FRE 3617, Centre de Recherche en Myologie, Service des Bases de Données, Institut de Myologie, AP-HP, Groupe Hospitalier-Universitaire La Pitié-Salpêtrière, Centre de Référence de Maladies Neuromusculaires Paris-Est, Paris, France

Excerpt

CLINICAL CHARACTERISTICS:

Emery-Dreifuss muscular dystrophy (EDMD) is characterized by the clinical triad of joint contractures that begin in early childhood, slowly progressive muscle weakness and wasting initially in a humero-peroneal distribution that later extends to the scapular and pelvic girdle muscles, and cardiac involvement that may manifest as palpitations, presyncope and syncope, poor exercise tolerance, and congestive heart failure. Age of onset, severity, and progression of muscle and cardiac involvement demonstrate both inter- and intrafamilial variability. Clinical variability ranges from early onset with severe presentation in childhood to late onset with slow progression in adulthood. In general, joint contractures appear during the first two decades, followed by muscle weakness and wasting. Cardiac involvement usually occurs after the second decade.

DIAGNOSIS/TESTING:

The three genes in which pathogenic variants are known to cause EDMD are EMD (encoding emerin) and FHL1 (encoding FHL1), which cause X-linked EDMD (XL-EDMD); and LMNA (encoding lamin A and C), which causes autosomal dominant EDMD (AD-EDMD) and autosomal recessive EDMD (AR-EDMD). For all forms of EDMD the diagnosis is based on clinical findings and family history. The diagnosis of X-linked EDMD also relies on failure to detect emerin or FHL1 protein in various tissues and molecular genetic testing of EMD or FHL1. The diagnosis of AD-EDMD and AR-EDMD also relies on molecular genetic testing of LMNA.

MANAGEMENT:

Treatment of manifestations: Surgery to release contractures and manage scoliosis as needed; aids (canes, walkers, orthoses, wheelchairs) as needed to help ambulation; treatment for cardiac arrhythmias, AV conduction disorders, congestive heart failure, including antiarrhythmic drugs, cardiac pacemaker, implantable cardioverter defibrillator (ICD); heart transplantation for the end stages of heart failure as appropriate; respiratory aids (respiratory muscle training, assisted coughing techniques, mechanical ventilation) as needed. Prevention of primary manifestations: Physical therapy and stretching to prevent contractures; implantation of cardiac defibrillators to reduce risk for sudden death. Prevention of secondary complications: Antithromboembolic drugs to prevent cerebral thromboembolism of cardiac origin in those with decreased left ventricular function or atrial arrhythmias. Surveillance: At a minimum, annual cardiac assessment (ECG, Holter monitoring, echocardiography); monitoring of respiratory function. Agents/circumstances to avoid: Triggering agents for malignant hyperthermia, such as depolarizing muscle relaxants (succinylcholine) and volatile anesthetic drugs (halothane, isoflurane); obesity. Evaluation of relatives at risk: Cardiac evaluation for relatives at risk for AD-EDMD and female carriers of XL-EDMD.

GENETIC COUNSELING:

EDMD is inherited in an X-linked, autosomal dominant, or autosomal recessive manner. XL-EDMD. If the mother of a proband has a 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 carriers. Female carriers are usually asymptomatic, but are at risk of developing a cardiac disease, progressive muscular dystrophy, and/or an EDMD phenotype. AD-EDMD. 65% of probands with AD-EDMD have a de novoLMNA pathogenic variant. Each child of an individual with AD-EDMD has a 50% chance of inheriting the pathogenic variant. AR-EDMD. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being neither affected nor a carrier. Prenatal testing for pregnancies at increased risk is possible if the pathogenic variant(s) have been identified in a family member.

Copyright © 1993-2017, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

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