Thomsen disease is a hereditary and familial lesion of the striated musculature, manifested by prolonged relaxation of the muscles after their contraction. In addition to the typical myotonic phenomenon, the disease is characterized by hypertrophic changes in the affected muscles, manifestation from the lesion of the hands, frequent involvement of facial muscles. Thomsen disease is diagnosed on the basis of anamnestic data, the results of neurological examination, EMG and ENG, molecular genetic research. Treatment is reduced to prescribing drugs that reduce the tonic reactions of muscles and normalize the ionic state of myofibrils.
General information
Thomsen disease is included in the group of hereditary myotonia, which also includes Rossolimo-Steinert-Kurschmann myotonia, Eilenburg congenital paramyotonia, Becker myotonia and a number of other diseases. Thomsen’s disease acquired its name in accordance with the surname of the scientist who described in detail its symptoms and the order of inheritance on the example of 4 generations of his family. 2 years before Thomsen (in 1874), Leiden gave the first description of the disease. Therefore, in modern neurology, the name Leiden-Thomsen disease is also used.
In patients with this type of myotonia, the dominant type of inheritance of the pathological autosomal gene is traced. According to various estimates, the incidence of the disease ranges from 3 to 7 people per 1 million population.
Etiology and pathogenesis
Thomsen disease refers to hereditary channelopathy. Like Becker’s myotonia, the disease is associated with a defect of the 7th chromosome, namely the CLCN1 gene, which determines the synthesis of the protein of chlorine ion channels of skeletal muscle myofibrils. The consequence of a violation of the synthesis of this specific protein is a reduced passage of chlorine ions into the myofibrils and their accumulation on the surface of the muscle fiber membrane (sarcolemma). The resulting bioelectric instability of the sarcolemma causes its excessive excitability. At the same time, the peripheral neuron functions without deviations, but the myofibrillic membrane reacts to the usual nerve impulse with increased excitation, which prevents the normal relaxation of the muscle fiber after its contraction. Moreover, the faster the contraction of myofibrils occurs, the more difficult its relaxation is. However, after a series of reductions, compensatory mechanisms are implemented, ion channels begin to function intensively and the situation normalizes.
Morphological changes in muscle tissue are nonspecific for Thomsen disease and are typical for most myotonia. There is a centralization of the sarcolemma nuclei, an increase in the cross-sectional area of myofibrils, indicating their hypertrophy. Electron microscopy determines hypertrophy of the sarcoplasmic reticulum, an increase in the size of mitochondria and a change in their shape, thickening of the telophragma.
Symptoms
In most cases, the manifestation of the disease occurs in early childhood. Leading in the clinic of the disease is the myotonic symptom complex, the so-called myotonic phenomenon. It is characterized by prolonged muscle relaxation after making a quick movement. Clinically, this is manifested by the inability to quickly make the next movement due to tonic spasm of the muscles involved in the previous motor act. It is noteworthy that after a series of active movements, the rate of muscle relaxation is normalized and the patient can move almost like a healthy person. A break in muscle work leads to the resumption of problems with muscle relaxation at the beginning of a new phase of motor activity.
Pathognomonic for Thomsen’s disease is its manifestation with pathological changes in the hands. Then myotonic manifestations spread to the musculature of the legs, mimic and masticatory muscle groups. As a result, tonic spasms are observed when walking abruptly, closing the eyes, closing the teeth, etc. movements. When trying to walk fast, patients lose their balance and may fall due to the development of general stiffness. Emotional experiences and being in the cold increase myotonic reactions.
The appearance of patients with Thomsen disease is peculiar. Due to diffuse muscular hypertrophy, they often have the physique of athletes. Their muscles are characterized by an excessively dense consistency, but have reduced strength. Muscular hypertrophy is a distinctive symptom of the disease, which makes it possible to differentiate it from Rossolimo-Steinert-Kurschmann myotonic dystrophy, accompanied by muscle atrophy.
Diagnostics
Since Thomsen disease usually manifests at an early age, the parents of a sick child turn primarily to a pediatrician, who directs them to consult a pediatric neurologist. To identify the myotonic symptom complex, the neurologist asks the examinee to quickly clench and unclench his fist several times. The slow unclenching of the fingers at the beginning of testing and the gradual normalization of movements during their repetition indicate in favor of myotonia. The presence of a myotonic phenomenon is indicated by the formation of a “roller” of local muscle contraction in response to tapping with a neurological hammer on the muscle. The neurological status reveals a decrease in muscle strength and the myotonic nature of tendon reflexes. Possible myotonic reaction of the pupils to light irritation.
Fundamental in the diagnosis of Thomsen disease are electrophysiological studies: electromyography and electroneurography. The first reveals repetitive high-frequency discharges specific to myotonia, and the second makes it possible to completely exclude damage to the animal nervous system.
Muscle biopsy allows you to study morphological changes in muscle tissue. Nevertheless, the hypertrophy of myofibrils detected in Thomsen disease and the centralization of their sarcolemma nuclei are also observed in other types of myotonia. In order to make an accurate diagnosis with verification of the type of myotonia, it is necessary to conduct a molecular genetic analysis to determine the defect of the CLCN1 gene.
Treatment
Modern medicine has not yet developed radical therapy for gene diseases. Therefore, the main task of treating Thomsen disease is to reduce its manifestations and slow down the progression of symptoms. To reduce tonic spasticity, drugs such as diphenine, phenytoin, carbamazepine are used. To maintain the ionic equilibrium of the membranes of myofibrils, calcium preparations are used in the form of drug therapy, electrophoresis, galvanization of the collar zone. For the same purpose, measures to reduce the potassium content in the body are recommended: a low-potassium diet, diuretic therapy. From diuretics, the appointment of acetazolamide is preferable, since, in addition to increased excretion of potassium in the urine, it also increases the permeability of the sarcolemma.
Massage and physical therapy are of particular importance in the complex treatment of Thomsen disease. They should be carried out with extreme caution in order to improve the metabolic processes of muscle tissue and at the same time reduce its tendency to tonic spasm.
Prognosis and prevention
Thomsen disease persists throughout life. The benign course and slow progression of the disease makes its prognosis relatively favorable. Patients, as a rule, remain able to work. However, their profession should not be associated with the need to make quick movements. Such people cannot work on the assembly line, be drivers, firefighters, policemen, etc.
The measures of primary prevention of Thomsen’s disease include counseling by a geneticist of a married couple planning pregnancy and having cases of the disease among relatives. Prevention of myotonic seizures is the exclusion of sudden motor activity, hypothermia, physical overload and emotional excitement.
