Emery Dreifuss muscular dystrophy is a hereditary muscular myodystrophy characterized by slow progression, early development of elbow contractures, retractions of the neck muscles and Achilles tendons, concomitant cardiac conduction disorders. The disease can be inherited, both linked to the X chromosome, and autosomal. Muscle weakness and hypotrophy are manifested mainly in the muscles of the lower leg and proximal parts of the arms. The diagnostic algorithm includes the study of neurological status, blood test, EMG and ENG, chest X-ray, ECG, echocardiography, genealogical analysis, DNA diagnostics. Treatment is symptomatic. Orthopedic surgeries and implantation of an electrocardiostimulator may be required.
General information
EmeryDreyfus muscular dystrophy is characterized by slower development of muscle weakness, early formation of contractures and tendon retractions, severe lesions of the cardiac conduction system requiring implantation of a pacemaker. Since 1961, the British neurologist Dreyfus and his American colleague Dr. Hogan have jointly studied a large family whose members suffered from myodystrophy, inherited linked to the X chromosome. Initially, researchers considered the disease to be a benign clinical variant of progressive Duchenne myodystrophy, however, during long-term observations, they came to the conclusion that it was necessary to isolate it into an independent nosological unit. Subsequent advances in genetics and biochemistry, which made it possible to establish the etiopathogenetic substrate of the disease, confirmed the arguments of Dreyfus and Hogan.
Causes
Emery Dreifuss muscular dystrophy is a genetically determined pathology and is represented by three variants: recessive X-linked and autosomal — dominant and recessive. The first variant is caused by mutations in the EMD gene located on the Xq26.3 region of the X chromosome and responsible for encoding the synthesis of the protein emerin. Autosomal variants occur with genetic aberrations in the region 1q21.2-q21.3 of the 1st chromosome in the LMNA/C gene encoding lamina A and C proteins. In the presence of one mutation in this gene, an autosomal dominant type of inheritance is noted, and with two mutations, an autosomal recessive type is noted.
Lamins A / C and emerin are part of the membrane of the nuclear envelope of myocytes, support its structure and functions. The lack of these proteins leads to a violation of the structure of muscle fibers, which is most pronounced in skeletal and cardiac muscle tissue. Observations show that with the same type of mutations, Emery Dreyfus muscular dystrophy can have various phenotypic manifestations, ranging from the mildest to the most severe clinical course.
Symptoms
As a rule, Emery Dreyfus muscular dystrophy manifests at the age of 5 to 16 years. The first symptoms of the disease are contractures of the elbow joints, retraction (shortening) of the muscles of the posterior neck group and Achilles tendons. Changes in the cervical muscles cause a forced tilting of the head back and restriction of the mobility of the spine in the cervical region. Shortening of the Achilles tendons leads to walking with support on the outer edges of the feet or with the feet on the toes.
Muscle weakness and hypotrophy usually appear later, are initially barely noticeable and are characterized by slow progression. First of all, the muscles of the peroneal group (located on the outside of the lower leg), the musculature of the shoulder girdle and the proximal parts of the upper extremities are affected. Unlike Becker’s progressive muscular dystrophy, Dreyfus myodystrophy is not characterized by pseudohypertrophy of the muscles of the lower legs. The facial muscles remain intact. In some cases, scoliosis is observed, caused by retraction of the paravertebral muscles and contractures of the intervertebral joints. At the same time, the curvature of the spine is stable and does not worsen with time.
The development of children before the onset of the disease is adequate to age norms. After the manifestation, myodystrophy slowly progresses until the age of 20, when the stabilization of the process is observed. In most cases, patients retain the ability to walk, climb stairs, get up from a squatting position without resorting to Govers techniques. The main factor aggravating the course of the disease is the pathology of the heart muscle with a violation of cardiac conduction.
Early signs of heart damage are detected only during daily ECG monitoring. Bradycardia attacks and syncopal conditions usually appear after the age of 20, in some cases they precede the onset of muscle weakness. There may be blockage of the legs of the Hiss bundle, AV block, atrial rhythm disturbances, dilated or hypertrophic cardiomyopathy. In the future, arrhythmia can cause a stroke.
Diagnostics
Dreyfus dystrophy is diagnosed by the joint efforts of specialists in the field of neurology and genetics. To identify cardiac pathology, a cardiologist’s consultation is required, in the presence of spinal deformities and contractures, an orthopedic consultation is required.
Neurological examination determines a moderate decrease in muscle strength in the proximal parts of the upper extremities (biceps and triceps of the shoulder, deltoid muscle, etc.) and distal parts of the legs (peroneal muscles), hypotension and hypotrophy of these muscle groups, tendon areflexia, complete preservation of sensory function. Additionally, electroneurography and electromyography are prescribed, the results of which indicate the primary muscular type of lesion and allow to exclude other neuromuscular diseases (myasthenia gravis, Guillain-Barre syndrome, ALS).
In the biochemical analysis of blood, there is a moderate or slight increase in the level of CPK (creatine phosphokinase). Microscopy of samples taken by muscle biopsy reveals the presence of hyper- and atrophied muscle fibers, the absence of nuclear staining of myocytes. Characteristic early changes on the electrocardiogram are a decrease in the amplitude of the P wave and an elongation of the PR interval. In the absence of ECG changes, Holter monitoring is recommended. An increase in the boundaries of the heart according to chest x-ray indicates the presence of cardiomyopathy. EchoCG allows to establish a more accurate cardiological diagnosis.
The final diagnosis of Dreyfus myodystrophy can be confirmed by a geneticist based on the results of genealogical analysis and DNA diagnostics. Differential diagnosis is carried out with Erba-Roth muscular dystrophy, Duchenne and Beckett myodystrophy, metabolic myopathy, dermatomyositis, and other diseases.
Treatment
Emery Dreifuss muscular dystrophy, like other gene diseases, does not yet have an effective specific treatment. The therapy carried out by neurologists is aimed at maintaining optimal metabolism of muscles and the peripheral nervous system, facilitating neuromuscular transmission, preventing thrombosis and cerebral embolization leading to stroke. As part of this, patients receive medication courses, including the appointment of ATP, pentoxifylline, vitamins B, neostigmine.
For long-term preservation of motor function by patients, regular massage and constant physical therapy classes are recommended. In complex symptomatic treatment, physiotherapy is effective — neostigmine electrophoresis, thermal procedures, hydrotherapy. When contractures are formed, orthopedic operations are performed to restore the ability of patients to move independently — tenotomy, Achilles tendon tenolysis, surgical removal of elbow contractures, etc.
Cardiological treatment plays a leading role in the therapy of Dreyfus dystrophy. Detection of bradycardia is an indication for implantation of an electrocardiostimulator. With the development of ventricular arrhythmia (usually in the late period of the disease), it is preferable to install a cardioverter defibrillator.
Prognosis and prevention
The prognosis of Dreyfus myodystrophy is mainly determined by the degree of cardiac disorders. Often patients die in middle age from sudden cardiac death. In other cases, increasing cardiac disorders lead to decompensation with the development of severe heart failure, which is the cause of death. Sometimes the death of a patient is associated with a stroke. Preventive measures include consulting a geneticist before a future pregnancy, if there are indications, prenatal diagnostics with subsequent fetal DNA analysis.