Myoclonic dystonia is a genetically heterogeneous condition that leads to muscle dysfunction (myoclonic hyperkinesis), as well as dystonia of the musculature of the upper body – neck, upper limb girdle. Symptoms of this condition are sharp muscle twitches (arms, neck, occasionally legs), especially when performing subtle movements. Then dystonia joins, which can manifest itself with a torticollis and an unusual pose of the patient. The diagnosis of myoclonic dystonia is based on the data of the patient’s current status and molecular genetic analysis. Treatment of the disease is symptomatic, includes benzodiazepines and anticonvulsants, sometimes botulinum toxin is used to eliminate spastic disorders.
Myoclonic dystonia (myoclonus-dystonia, ethanol-sensitive myoclonia) is a genetic condition of various nature characterized by muscle dysfunction with the development of hyperkinesis and dystonia. It was first described back in 1940 by Benedek, but he could not identify the pathology as a separate type of myoclonia, this was done by Daubets and Peters in 1966. Currently, geneticists have determined that this condition is heterogeneous, that is, mutations of various genes are responsible for its development, many of which have not yet been identified. For this reason, the mechanism of inheritance of myoclonic dystonia is unclear. In most cases, autosomal dominant transmission of pathology is noted, while there are indications of the presence of maternal imprinting, in which a defective gene transmitted from the mother does not lead to the development of the disease. The incidence of myoclonic dystonia is estimated at 1:500000.
It is reliably known that myoclonic dystonia has a genetic nature, while there are both hereditary family cases and sporadic gene mutations. Until recently, only one gene was known whose mutations cause the development of this disease – SGCE, localized on the 7th chromosome. In the European population, defects of this gene occur in 20-30% of patients with myoclonic dystonia. The product of its expression is the protein sarcoglycan-epsilon, belonging to the group of transmembrane proteins found in skeletal muscles, myocardium and neurons of a number of structures of the central nervous system.
The functions of the protein are currently unclear, it is assumed that it is part of the so-called dystrophin-glycoprotein complex, whose tasks in the body are also unknown. For this reason, the pathogenesis of myoclonic dystonia caused by a mutation of the SGCE gene has been little studied. Even less is known about the form of the disease, which is associated with the 18th chromosome – even the gene that leads to the development of this pathology has not been established in relation to it.
More recently, there have been indications that in some patients with myoclonic dystonia, mutations of the DRD2 gene located on the 11th chromosome were observed against the background of the absence of defects in SGCE. The gene encodes the sequence of one of the dopamine (D2) receptors, which is predominant in some basal nuclei of the brain. Basically, in myoclonic dystonia, a missense mutation of the Val154Ile gene DRD2 is detected, leading to a change in the structure of the receptor. As a result, many processes of control over muscle tone change, which is clinically manifested by hyperkinesis and dystonia. In addition, phobias, obsessive states and panic attacks occur with this disease.
Indications of an increased predisposition of persons with mutations of the above genes to alcoholism are only partially justified. Drinks based on ethyl alcohol can weaken the symptoms of myoclonic dystonia, for this reason, patients in some cases consume alcohol in moderate doses to alleviate their condition, over time this can cause serious dependence.
At the birth of a child and in the first years of life, myoclonic dystonia does not manifest itself in any way, it is not possible to notice the presence of this condition. The first signs of the disease occur at the age of 15-30 years, the symptoms of pathology increase quite quickly, but in the future its tendency to progression is not detected. At the initial stages of myoclonic dystonia, hyperkinesis of the muscles of the upper half of the trunk develops – the shoulder girdle, arms, neck, and occasionally the face. Sometimes twitching develops into convulsions, often having a twisting character and a different frequency of occurrence. Hyperkinesis and convulsions in myoclonic dystonia rarely manifest themselves at rest, mainly their appearance is associated with small and precise movements – writing or drawing. Muscle twitching is quite sharp, often described by patients as “lightning-fast”.
Another manifestation of myoclonic dystonia is muscle tone disorders, which often affect the neck, upper extremities, and sometimes the muscles of the larynx and legs. Focal and spastic dystonia, which has an asymmetric character, is most often noted, with the development of torticollis on the neck muscles in such cases. As a rule, after the onset of dystonia, it does not increase and does not affect new muscle areas. In some cases, one of the manifestations of myoclonic dystonia may be a tremor of the hands. Dysarthria is also possible due to a violation of the functions of the laryngeal muscles. Other muscle symptoms in this disease are usually not determined.
With myoclonic dystonia, various mental disorders are often revealed: phobias, obsessive states, panic attacks, depression. Ethanol is able to significantly reduce the severity of hyperkinesis and dystonia, so many patients consume various amounts of alcoholic beverages. In the absence of medical supervision, this leads to persistent alcohol dependence and concomitant disorders. Therefore, mental symptoms in myoclonic dystonia may have a different nature – primary, due to a violation of biochemical processes in the nervous system due to a genetic mutation, and secondary, caused by excessive alcohol consumption.
Diagnosis and treatment
To determine myoclonic dystonia, data from the patient’s examination results and molecular genetic analyses are used. During the examination, tremors of the hands, clonic hyperkinesis of the muscles, shoulder girdle, arms and neck are revealed, which are intensified by physical exertion or performing movements that require complex coordinated work of bundles of muscle fibers (for example, drawing). Torticollis may also be detected due to spastic dystonia of the musculature, in more severe cases, an unusual position of the patient’s body is determined. In the patient’s anamnesis, cases of convulsive seizures and other neurological symptoms are detected – all this also indirectly indicates the presence of myoclonic dystonia.
A psychiatrist or a narcologist is often involved in the process of diagnosing myoclonic dystonia, since mental disorders and problems with narcotic substances are often detected in this condition. During the examination of the patient, a depressive or depressed state, obsessions and phobias may be recorded. Panic attacks are often associated with convulsive seizures, after which patients with myoclonic dystonia begin to overcome the fear of death, fear for their health or life. Examination by a narcologist sometimes reveals signs of alcohol or (much less often) benzodiazepine addiction – the latter often occurs with improper treatment or violation of the drug regimen.
Molecular genetic diagnosis of myoclonic dystonia is currently not widely used. This is largely due to the fact that genetic defects leading to this condition (mutations of the SGCE and DRD2 genes) have been reliably established for only about a third of cases of the disease. However, a number of clinics still offer the definition of myoclonic dystonia by genetic methods by direct sequencing of the sequences of the above genes. Prenatal diagnosis is necessary in cases where the father of the child suffers from myoclonic dystonia – due to imprinting, the transmission of a defective gene from the mother to the offspring is extremely rare. Differential diagnosis is performed with familial myoclonia (Unferricht-Lundborg disease), Tourette’s syndrome, Wilson’s disease, and other primary and secondary forms of dystonia.
There is no specific treatment for myoclonic dystonia, symptomatic therapy is used. In the presence of tremor and pronounced hyperkinesis, drugs from the benzodiazepine group have a good effect, but they can be prescribed only after consulting a narcologist – it is important that the patient does not have alcohol or benzodiazepine dependence. Convulsive seizures that occur with myoclonic dystonia are eliminated with the help of traditional anticonvulsant therapy. Spastic dystonia of muscles and especially torticollis can be significantly weakened by injections of small doses of botulinum toxin for partial chemical denervation of muscle tissue. The effectiveness of these therapeutic measures varies in different patients with myoclonic dystonia, which is due to the significant genetic and phenotypic heterogeneity of this condition.
Prognosis and prevention
The prognosis of myoclonic dystonia regarding the survival of patients is quite favorable – the condition has no tendency to progression of symptoms, does not affect vital systems and organs. However, the quality of life of patients can significantly decrease due to hyperkinesis, which often makes it impossible to perform fine movements (for example, writing), dystonic torticollis and other symptoms of the disease. In addition, the prognosis of myoclonic dystonia worsens the increased risk of developing alcohol dependence – even a socially well-off person may become addicted to alcoholic beverages due to the fact that they alleviate neurological symptoms. The risks are further increased by the patient’s psychoemotional disorders, which increase the likelihood of developing alcohol dependence and can cause serious neurosis. There is no specific prevention of myoclonic dystonia, if the disease occurs, all doctor’s prescriptions should be followed.