Limb-girdling Dystrophy: Causes, Symptoms & Treatment

Limb-girdle dystrophy is a group of myopathies of the limb girdle. The disorders are caused by genetic mutations and are considered incurable. The goal is maintenance of mobility through physical and occupational therapy.

What is limb-girdle dystrophy?

The shoulder girdle and pelvic girdle together make up the limb girdle. Accordingly, limb-girdle dystrophy refers to a group of myopathies of the pelvic and shoulder girdles that are associated with paralysis in these areas. The myopathies are muscle diseases of the striated skeletal muscles. In addition to muscle paralysis, myopathic limb-girdle dystrophy presents with the typical symptoms of muscular dystrophy. Muscular dystrophies manifest themselves in remodeling processes within the muscle tissue. The diseases from the group of limb-girdle dystrophies are genetically determined and show clinical, as well as genetic heterogeneity. They are caused by different gene mutations. Some diseases from the group are also caused by the same gene mutations, but show clinically a variable picture. The onset of a limb-girdle dystrophy can be as early as infancy. Just as well, the dystrophy can manifest itself only in high adulthood. In addition to mild courses, severe courses of limb-girdle dystrophies have been observed. The disorders as a whole are extremely rare diseases, with an estimated prevalence of approximately between one case in 14500 and one case in 123000.

Causes

Each disease in the group of limb-girdle dystrophies results from a genetic mutation. Autosomal dominant forms of the disease are sometimes rare and do not manifest until adulthood. These forms of the disease can be caused by different mutations, e.g. in the LGMD1A gene at locus 5q22-q34, in the LGMD1B gene at locus 1q22, in the LGMD1C gene at locus 3p25.3 or in the

LGMD1D gene at locus 6q23. Mutations in the LGMD1E gene, LGMD1F gene, LGMD1G gene, and LGMD1H gene at locus 3p25.1-p23 may also be causative. The autosomal recessive form of the disease manifests itself in some cases in early childhood and usually has a more severe course. The causative mutations range from the LGMD2A, LGMD2B, LGMD2C, LGMD2D, LGMD2E, and LGMD2F genes to the LGMD2G, LGMD2H, LGMD2I, LGMD2J, and LGMD2K genes. In addition, in some

patients, causative mutations were found in the LGMD2M, LGMD2N, LGMD2O, LGMD2P , LGMD2Q, and LGMD2R genes. Equally well, limb-girdling dystrophy may result from mutations in the LGMD2S, LGMD2T, LGMD2U, LGMD2V, or LGMD2W genes. The gene products encoded by each gene range from proteins to enzymes. To list them all here is beyond the scope of this article.

Symptoms, complaints, and signs

Symptoms of limb-girdle dystrophy depend on the mutated gene and its gene product in each individual case. However, paralysis of the muscles on the limb girdle occurs in approximately every disease in the parent group and may vary in severity depending on the mutation. In some limb-girdle dystrophies, there is only muscle weakness of the limb girdle. In others, severe paralysis occurs, some of which may also affect the face or legs. In exceptional cases, the heart muscle is involved in the symptomatology. Especially when limb-girdle dystrophy begins in early childhood, the motor development of patients is usually disturbed. The muscle weaknesses and paralyses may be associated with cramps. In some cases, muscle breakdown also occurs. Muscle pain is also a characteristic phenomenon in many subtypes of the disease. In certain mutations, symptoms of limb-girdle dystrophy may be associated with symptoms of mental retardation. Whether the pelvis, legs, calves, or shoulder area are more likely to be affected by symptoms such as muscle weakness depends on the causative mutation in each individual case.

Diagnosis and progression

In diagnosing limb-girdle dystrophy, the physician is likely to have an initial suspicion anamnetically. As part of the workup, he or she usually arranges for [[electromyography]], which yields nonspecific evidence of chronic damage to the muscles. Imaging techniques such as computed tomography and magnetic resonance imaging are suitable for closer visualization of affected muscle groups.An increase in creatine kinase may be indicative of dystrophy. In most cases, the suspected diagnosis is confirmed by immunohistochemical or molecular genetic analysis of the muscle biopsy. Molecular genetic analysis can additionally narrow down which disease from the group of limb-girdle dystrophies is involved. The prognosis depends on the causative gene mutation and the age of manifestation. The earlier the manifestation, the less favorable the prognosis usually is. In addition, involvement of the myocardium severely worsens the prognosis. Walking ability is maintained in some subgroups of dystrophy until about 25 years after disease onset. In some cases, science also assumes an individual course that even promises a longer ability to walk. In other cases, an early lethal course applies.

Complications

Limb-girdling dystrophy is a genetic muscle disease that develops progressively. The disease affects the muscles of the shoulder and pelvic girdle. This so-called limb girdle forms the striated skeletal muscles that support the musculoskeletal system. As the symptom progresses, the musculoskeletal system is increasingly shut down, leading to serious complications. Among other things, muscle paralysis develops, which not only affects the extremities, but can also affect the face and speech motor function. For the patient, limb-girdle dystrophy has a very life-limiting effect. If the symptom breaks out in childhood, it can even negatively affect the activity of the heart muscle as well as motor development. Concomitant symptoms include cramps, muscle pain, muscle breakdown and loss of gait. A diagnosis made at an early stage can determine the type of mutation and also whether the symptom is more pronounced in the lower or upper body. There are patients whose entire body is affected by the symptom. Therefore, the sooner a limb-girdle dystrophy is diagnosed, the more effective the medical therapy can be. There is no cure for the disease at present. Only the course and a relatively certain mobility can be influenced by specific ergo- and physiotherapeutic measures. After the onset of the disease, the patient usually has about 25 years until complete loss of gait occurs.

When should you see a doctor?

People suffering from paralysis symptoms should always see a doctor. If limb-girdling dystrophy has already been diagnosed in other relatives within the family, a doctor should be consulted for clarification. If the shoulders or pelvis are affected, help is needed. If there are limitations in movement, decreased ability to perform, or everyday activities can no longer be performed as usual, help is needed. If there is unsteadiness in gait, an increased risk of accidents, or a loss of usual mobility, a visit to the doctor is required. There is also cause for concern in the case of complaints of the heart muscle. If there are disturbances of the cardiac rhythm system, increased fatigue or drowsiness, a physician must be consulted. Muscle weakness or cramping of the body is considered unusual and should be investigated by a physician. If the discomfort spreads further to the legs, calves or face, a visit to the doctor should be made. If the affected person suffers from psychological complaints in addition to the physical impairments, the support of a therapist should be sought. In the case of anxiety, a phobic demeanor, lowered self-esteem, or social withdrawal, consultation with a physician or therapist should be sought. Behavioral abnormalities, a change in personality, apathy, a persistent loss of enjoyment of life, or apathy are reasons to consult a therapist.

Treatment and therapy

Causal therapy is not available for patients with limb-girdling dystrophy. Also, established symptomatic therapies using drug administration have not been reported for any of the limb-girdle dystrophies. Physiotherapeutic measures are the focus of symptomatic therapy and are intended to preserve the remaining muscle strength. In occupational therapy, patients are also trained in everyday movements to prevent falls and contractures. Maximum strength training has an unfavorable effect on the course of the disease and should be avoided.As soon as it becomes necessary, patients are provided with aids in the form of orthoses, walking sticks or a rollator. They learn how to use these aids properly in occupational therapy. After a certain stage of the disease, the wheelchair is usually unavoidable. Wheelchair training can also take place as part of physiotherapy care. If patients develop deformities as a result of the disease, surgical treatment measures to restore the ability to walk may be considered. As soon as speech motor skills become impaired, patients may receive speech therapy. If patients are immobile for a long time due to certain life circumstances or operations, they often lose their remaining walking ability completely. Therefore, immobile phases should be avoided as far as possible. If there is involvement of the myocardium, for example, treatment of conduction disorders may take place.

Outlook and prognosis

The outlook can be described as mixed. Medical science has not yet developed a procedure to prevent shoulder and pelvic girdle muscle disease. To date, limb-girdle dystrophy has no cure. However, preservation of mobility can be promoted by ergo- and physiotherapeutic measures. In the best case scenario, patients then have 25 years of life left before the loss of gait sets in. Early diagnosis gives doctors and therapists plenty of leeway to curb progression of the disease. A less good prognosis usually results for sufferers who are diagnosed with the typical symptoms at an advanced stage. Paralysis and muscle pain are indicative of this. Complications are regularly caused by the disease of the heart and respiratory muscles. The life span is usually shortened considerably. The outlook for the diagnosis of limb-girdle dystrophy also includes a look at the circumstances of life. Affected persons must sooner or later be prepared to make use of assistive devices. In the beginning, patients can manage with a walking stick. If the disease develops further, the use of a wheelchair is inevitable. Even with weaker manifestations, restrictions in everyday life are common. The quality of life is at a low level.

Prevention

At best, limb-girdling dystrophy can be prevented to date through genetic counseling during family planning.

Follow-up care

In the case of limb-girdle dystrophy, there are hardly any measures or options for aftercare available to the affected person. As a rule, this disease cannot be completely cured because it is a genetic disease, so it can only be treated purely symptomatically and not causally. For this reason, early diagnosis is especially important to prevent further complications or discomfort. As a rule, early diagnosis always has a positive effect on the further course of limb-girdle dystrophy. Treatment is carried out with the help of physiotherapy or physiotherapy measures. In this way, the mobility of the affected person can be increased again. In many cases, the affected person can also perform the exercises from these therapies themselves in their own home and thereby possibly accelerate the healing process. The help and care provided by the patient’s own family and by friends and acquaintances can also make the affected person’s everyday life much easier. Contact with other patients of limb-girdle dystrophy usually has a positive effect on the course of the disease, so that information can be exchanged. The life expectancy of the affected person is usually not reduced by the disease.

What you can do yourself

Patients counter the limitations of their mobility caused by limb-girdle dystrophy with their own initiative and perform physiotherapy exercise sessions even at home. They first practice the corresponding training options with a physiotherapist, whose treatment they usually receive on an ongoing basis. The additional performance of strengthening exercises at home improves mobility and thus to a certain extent increases the general quality of life. If the mobility restrictions are too severe, various walking aids are used for support. Patients also use these at home and for outside activities, making it much easier for them to get around.They also use them to prevent certain accidents and injuries, as the walking aids provide more safety during movement. In principle, patients with limb-girdle dystrophy take care not to overstrain themselves and to maintain sufficient rest periods so that the muscles are not overstrained. If surgical intervention is necessary, the patients themselves then help to quickly retrain various movement patterns. These exercises are done in consultation with the doctor and reduce the risk of losing the ability to walk completely after the operation. In this context, physiotherapeutic treatment begins shortly after the operation, the success of which the patient promotes through his or her own initiative.