|
Emery-Dreifuss muscular dystrophy (EDMD) is characterised by muscular weakness and atrophy, with early contractures of the tendons and cardiomyopathy. Prevalence is estimated at 1 in 300,000. The clinical triad is comprised of 1) contractures of the Achilles, elbow and neck tendons, beginning during early childhood and worsening to result in limited joint movement; 2) slowly progressive muscle weakness and atrophy (initially with a humeroperoneal distribution but later becoming more diffuse); 3) cardiac anomalies (conduction defects, rhythm disturbances and dilated cardiomyopathy) usually manifest after age 20 and may lead to sudden death (sometimes the inaugural symptom of the disease) and ischemic accidents due to embolism. Disease course and severity vary between families and between patients from the same family. Several modes of transmission have been reported: X-linked and autosomal dominant or recessive. Two causative genes have been identified encoding ubiquitous nuclear envelope proteins: emerin (EMD; Xq28) for X-linked EDMD and lamin A/C (LMNA; 1q21.2) for EDMD with autosomal transmission. Around 45% of patients do not carry mutations in these genes suggesting other causative genes remain to be identified. Diagnosis relies on recognition of the clinical triad (although the cardiac manifestations may be absent at onset). Muscular imagining may reveal isolated involvement of the soleus, suggestive of the initial stages of disease. For X-linked forms, immunodetection of emerin in various tissues (muscle, lymphoblasts, skin) reveals an absence or reduction of the protein. The diagnosis can be confirmed by detection of EMD mutations. For autosomal forms, molecular analysis of LMNA is the only approach for confirming the diagnosis. The main differential diagnoses include other forms of myopathy with contractures, with or without cardiac involvement (Bethlem myopathy, SEPN1 and FKRP-related myopathies); the desmin-related myopathies; proximal myotonic myopathy; and certain forms of LGMD with cardiac involvement (see these terms). Genetic counselling depends on the mode of transmission and on whether the mutation has been identified. Prenatal diagnosis is possible when the causative mutation is known. Management should include: 1) orthopaedic measures (orthopaedic apparatus, surgery for the Achilles tendon contractures and scoliosis); 2) treatment of the cardiac disease: antiarrhythmic agents, diuretics, ACE inhibitors, cardiac implants (stimulator, defibrillator), heart transplants in case of terminal cardiac insufficiency and 3) treatment of the respiratory complications (nasal ventilation, tracheotomy). Prognosis depends on the severity of the tendon contractures and of the cardiac involvement. Patients with severe forms of the disease may loose the capacity to walk. |