Proximal myotonic myopathy is a hereditary disorder associated with muscle weakness in the proximal skeletal muscles and eye problems. Usually, the first symptoms appear between the ages of 40 and 50. Currently, only symptomatic treatment is available.
What is proximal myotonic myopathy?
Proximal myotonic myopathy is a genetic muscle disorder that usually does not manifest until the middle years of life. To date, there have been no cases of congenital disease. The disease has also not been observed in children. Only a very rare juvenile form may occur. In addition to proximal muscle weakness, eye problems also occur, manifested by visual impairment. Other names for this disease include myotonic dystrophy type 2 or Ricker’s disease. The course of this disease is milder than that of myotonic dystrophy type 1 (Curschmann-Steinert disease), which is also hereditary. However, Ricker disease occurs less frequently than Curschmann-Steinert disease. Thus, the prevalence is estimated to be 1 to 5 per 100,000 individuals. In Germany and the USA, the prevalence is somewhat higher. The reason for this could be the first appearance of the corresponding mutation in Central Europe. Because of its genetic cause, the disease cannot be treated causally, but only symptomatically.
Causes
The cause of proximal myotonic myopathy is thought to be a defect in the ZNF9 gene on chromosome 3. This gene encodes a so-called zinc finger protein, which contains zinc as a central atom. The corresponding protein interacts with DNA or RNA and thus influences the gene expression of various genes. The encodable part of the gene is not changed, but the CCTG repeat sequence expands. This means, therefore, that an additional CCTG sequence is incorporated in the non-codable region of the gene, which in turn influences gene expression for the ZNF9 gene. In this case, the corresponding protein is not genetically altered, but it is not present at the optimal concentration. Anticipation is also observed in some cases. Anticipation marks an earlier onset of the disease in the offspring. Moreover, the symptoms are then more pronounced in them. This is caused by more built-in CCTG repeats, which can expand more and more from generation to generation. The expansion of CCTG repeats or tetranucleotide repeats in general is also genetically determined. However, anticipation does not always occur because the number of CCTG repeats does not necessarily correlate with the age of onset of the disease. Proximal myotonic myopathy is inherited in an autosomal dominant manner. In this case, the disease is passed directly from one generation to the next.
Symptoms, complaints, and signs
Proximal myotonic myopathy can be manifested by a variety of symptoms. The degree of expression of the disease signs varies widely. One of the most important features is the development of proximal muscle weakness, which is usually the determining factor in the diagnosis of the disease. The muscles of the pelvis and shoulder girdle are often affected. Muscle weakness is often accompanied by severe muscle pain (myalgias). In 75 percent of cases, increased muscle tension (myotonia) occurs, which is only slowly reduced. Much less frequently (about 12 percent), the facial muscles are also affected. Tremor is observed in one third of cases. The heart is also frequently affected. Cardiac arrhythmias and disturbances in impulse transmission occur. In the eyes, cataracts (cataracts) appear, leading to deterioration of visual acuity. Furthermore, hyperhidrosis (increased sweating), hyperthermia (increased heat production), reduction of the testicles (testicular atrophy) or even diabetes may develop. Sometimes central nervous disorders, hypogammaglobulinemia (deficiency of gamma globulins), or bile outflow disorders are also observed. Malignant hyperthermia is a complication. This can be triggered during anesthesia by inhalation narcotics, depolarizing muscle relaxants or even stress. Symptoms of this complication include palpitations, respiratory distress, cyanosis, muscle rigidity, acidosis, or hyperkalemia. Finally, a sharp rise in temperature takes place, which can lead to protein denaturation and circulatory failure.
Diagnosis and course of the disease
To diagnose proximal myotonic myopathy, electrical muscle activity is measured on an EMG (electromyogram). If monotonous volleys reminiscent of a dive-bombing sound occur, muscle disease is present. For more precise differentiation, direct gene testing is performed in the leukocytes. Other examination methods include the fist closure test and the percussion test. In the fist closure test, delayed opening of the hand after a closed fist indicates myotonia. The same is true if muscle contractions that last for a few seconds occur when the affected muscles are tapped (percussion).
Complications
In this condition, affected individuals usually suffer from muscle weakness. In most cases, the symptoms do not occur until late in life, so direct prevention or early treatment of this condition is not possible. Unfortunately, no causal treatment is possible either, so that only the symptoms of this disease can be limited. In this case, the patients suffer from a strongly developed muscle weakness. There is severe pain in the muscles, which occurs mainly under stress. In addition, this disease also causes muscle atrophy, which leads to a significantly reduced quality of life. The muscles in the face are particularly affected, so that the patient can no longer move them and thus also no longer control his facial expression. Likewise, those affected by this disease suffer from tremor and heart problems. In the worst case, cardiac arrest can occur. Also complaints at the eyes and a clearly reduced visual acuity occur thereby and complicate the everyday life of the concerning. No complications occur during the treatment itself. However, only the symptoms can be partially limited. A complete cure is usually not possible. It is also possible that the life expectancy of the affected person is reduced due to the disease.
When should you see a doctor?
People who are in adulthood and have severe muscle problems should have a checkup with a doctor. If the symptoms are due to physical overexertion, adequate rest and a restful night’s sleep are usually sufficient. This is followed by relief of the symptoms or spontaneous healing. A visit to the doctor is not indicated in these cases. However, if the symptoms persist unabated for several days or increase in intensity, a doctor is needed. A decrease in physical performance, limitations in mobility, and twitching of muscle fibers should be examined and treated. A persistent experience of stress, inner restlessness, a general feeling of illness as well as disturbances of the heart rhythm should be presented to a doctor. If there are sleep disturbances, daily requirements cannot be fulfilled or the well-being decreases, there is a need for action. If there are restrictions in vision, a decrease in visual acuity and an increased risk of accidents and injuries, the observations should be discussed with a doctor. Of concern are a reduction in the size of the testicles, an increase in perspiration or an unusual sensation of warmth inside the body. General dysfunction, discomfort in the pelvis or shoulders, and irregularities in the facial muscles should be presented to a physician. If there is muscle pain, repetitive tension, or a feeling of malaise, a physician is needed.
Treatment and therapy
Causal therapy for proximal myotonic myopathy is not currently available. So far, only symptomatic treatments can take place. This mainly involves physiotherapeutic measures, which can maintain walking ability until the age of 60. Multidisciplinary care and control is also important. Here, especially the monitoring of the heart plays a major role, because cardiac involvement is often crucial for the prognosis of the disease. If malignant hyperthermia occurs, life-saving measures such as ventilation, administration of dantrolene (a muscle relaxant), cooling of the body, and treatment of acidosis under intensive medical monitoring should be initiated immediately.
Prevention
Preventive measures to prevent the onset of proximal myotonic myopathy in the presence of a genetic predisposition do not currently exist. The disease is inherited in an autosomal dominant manner.If one parent suffers from this disease, there is a 50 percent probability that the offspring will also be affected. Therefore, if there is a family history of the disease, it is advisable to seek human genetic counseling.
Follow-up
Currently, only symptomatic follow-up can be given for proximal myotonic myopathy. This is mainly aimed at reducing the painful concomitant symptoms of the disease. Physiotherapeutic sessions are suitable for this purpose. These counteract the advancing muscle atrophy and weakness and help to maintain walking ability for as long as possible. Regular training sessions and special exercises help to stabilize the body. Nutrition plays an important role. A healthy diet provides the body with all the important nutrients. Furthermore, psychological support helps patients maintain their inner calm and a more positive attitude despite the disease. Self-help groups can also help individuals come to terms with the disease with the help of others affected. At home, occupational therapy with the use of various aids such as shower chairs, booster seats, or graspers can make patients’ daily lives easier. After the disease with proximal myotonic myopathy, regular follow-up visits to the doctor are important to monitor the heart as well as muscle atrophy and to detect decreased vision in time. Unfortunately, the prognosis in proximal myotonic myopathy is rather negative. Since it is a genetic disease, a complete cure is currently impossible. Especially the progressive muscle atrophy reduces the quality of life. This atrophy can also lead to a lower life expectancy.
What you can do yourself
Proximal myotonic myopathy is a genetic condition. The affected person has no means to cure himself of this disease. Through lifestyle and various techniques, the organism can be positively supported, but freedom from symptoms does not occur. The musculature should be the focus of targeted training. Although the disease causes severe impairments, it is advisable to stabilize the muscular system daily in individual exercises to the best of one’s ability. The training sessions should be tailored to the needs and limitations of the body. It is important to build up a sense of achievement, as this promotes motivation. A fundamentally positive attitude toward life is very helpful in coping with everyday discomfort. Attention should focus on pleasant experiences and promoting a sense of well-being. The use of relaxation techniques can be applied in strengthening mental power. Through meditation, autogenic training or yoga, existing stressors are reduced and at the same time the patient’s inner life is strengthened. This should help to improve the handling of the disease in everyday life. Social withdrawal is to be avoided. Joint activities are perceived by patients as pleasant and uplifting. The exchange in self-help groups brings mutual strengthening and support.
