Emery–Dreifuss muscular dystrophy

Humeral muscle atrophy and elbow contracture in person with EDMD

The classic triad of EDMD consists of early contractures, muscle weakness, and heart involvement, typically manifesting in adolescence.[1][7]

Contractures often manifest before weakness, and they can be more disabling.[1] They tend to fix the elbow into flexion and ankle into plantarflexion via Achilles tendon shortening.[8] The spine is also affected, with limited neck flexion initially, and eventually the entire spine can become fixed into extension, referred to as a rigid spine.[8] Elbow and neck contractures seldom occur in other diseases.[1] Eventually, orthopedics (walker, cane) may be needed.

The weakness is slowly progressive and preferentially involves the muscles that overlie the humerus bone (biceps and triceps muscles) and those situated on the outside of the lower leg (peroneal).[8] Later, the muscles that position the scapula can be weakened, completing a pattern that is termed 'scapulohumeroperoneal'.[8][1] Weakness of the scapular fixators can cause a winged scapula,[1] which can impair the ability to lift the arms over the head and can be painful. Weakness of the peroneal muscles can result in toe walking, which can present in the first decade of life.[1] Facial, hand, and thigh muscles can be affected, although less often.[1] Calf hypertrophy can occur.[1]

Involvement of the heart occurs in almost all cases, presenting as syncope in second or third decades, or as sudden cardiac death.[1] A multitude of cardiac arrhythmias can result, requiring a pacemaker often by age 30 years.[1] Reported arrhythmias include bradycardia, atrial fibrillation/flutter, atrioventricular conduction defect, and atrial paralysis.[1] Later in the disease, cardiomyopathy can occur.[1] Sometimes, cardiac involvement is the predominant manifestation of EDMD, with minimal involvement of the skeletal muscles.[1]

Mutations in the one of several genes cause the various types of Emery–Dreifuss muscular dystrophy.[2] Mutation of the EMD or LMNA gene is the cause in 40% of cases.[3] Each gene implicated in EDMD provides instructions for making a protein that is associated with the nuclear envelope, which surrounds the nucleus of a cell. The nuclear envelope regulates the movement of molecules into and out of the nucleus, and researchers believe it may play a role in regulating the activity of certain genes.

Mutations of the genes SUN1 and SUN2 have each been shown to cause EDMD in single cases.[3] TTN has also been associated with EDMD phenotype.[3]

• Protein structures
• 
  Protein LMNA
• 
  Protein EMD
• 
  Protein FHL1

Depiction of nuclear envelope and its proteins, many of which are implicated in EDMD

Genetic mutations causing EDMD affect proteins comprising the nuclear membrane.[3] Possibly, in all EDMD subtypes there is impaired protein importation into the nucleus.[3] Another possibility is that in all subtypes, there is a loss of nuclear structural integrity.[3]

Hemoxylin & eosin stained muscle biopsy showing variable muscle fibre sizes in an 8 year old male with EDMD

A positive genetic test in a person with the signs and symptoms of EDMD provides definitive diagnosis.[7] Genetic testing can involve single-gene testing or genomic testing.[7] Auxiliary testing can include the following:[7]

ACE inhibitor

Following diagnosis, extent of disease should be established in regards to the heart, the lungs, and the muscles/bones (musculoskeletal). Metabolic functions should also be assessed, as lipodystrophy can co-occur with EDMD, by measuring levels of sugar, cholesterol, and triglycerides in the blood. Tests useful for heart evaluation include electrocardiography (EKG), echocardiography (echo), cardiac MRI, and electrophysiology studies. Musculoskeletal function can be assessed by a physical therapist or orthopedist.

Regardless of extent of disease, cardiac and respiratory complications should be monitored for. EKG, holter, and echo are recommended yearly, and additional tests can be indicated depending on heart involvement. Pulmonary function tests (PFTs) are recommended every 2–3 years, or yearly in those with respiratory involvement.

Although the root cause of EDMD is not currently treatable, its manifestations and complications can be treated. Heart involvement can be addressed with medications (antiarrhythmics, beta-blockers, and ACE inhibitors), pacemakers, defibrillators, and sometimes heart transplantation. Affecting breathing can be addressed with physical therapy and, later in disease, mechanical ventilation. Contractures and scoliosis can be addressed with orthopedic surgery. Mobility can be improved with physical therapy, occupational therapy, and mechanical aids (canes, orthoses, wheelchairs).[7][19]

It is rare, affecting 0.39 per 100,000 (1 per 250,000) people.[3]

• Laminopathies
• Noncompaction cardiomyopathy

• Manila, S.; Recan, D.; Sewry, C. A.; Hoeltzenbein, M.; Llense, S.; Leturcq, F.; Deburgrave, N.; Barbot, J.-C.; Man, Nguyen thi (1998-05-01). "Mutations in Emery–Dreifuss Muscular Dystrophy and their Effects on Emerin Protein Expression". Human Molecular Genetics. 7 (5): 855–864. doi:10.1093/hmg/7.5.855. ISSN 0964-6906. PMID 9536090.
• Ziat, Esma; Bertrand, Anne T. (2015-01-01). "FHL1 protein isoforms in Emery–Dreifuss muscular dystrophy". Orphanet Journal of Rare Diseases. 10 (2): O18. doi:10.1186/1750-1172-10-S2-O18. ISSN 1750-1172. PMC 4652543.