Dystroglycanopathies are among the hereditary muscular dystrophies. They are a group of muscle disorders with varying symptoms, but all arise from disorders of specific glycosylations. There are currently no causal treatments for any of the dystroglycanopathies.
What are dystroglycanopathies?
Dystroglycanopathies represent hereditary muscular dystrophies based on metabolic disorders of glycosylation reactions. They are very rare disorders with muscle weakness and various other physical or mental impairments. Life expectancy is usually not very long. Dystroglycanopathy is a collective term for a heterogeneous group of very rare muscular dystrophies. Some diseases have even been described only once so far. Dystroglycanopathies include muscle-eye-brain disease, muscular dystrophy type Fukuyama or Walker-Warburg syndrome. This group also includes very rare forms of limb-girdle dystrophies such as limb-girdle dystrophy 2P or limb-girdle dystrophy 2I. Muscular dystrophies are diseases that are always associated with increasing muscle weakness and wasting. In all muscular dystrophies, muscle wasting is irreversible. Due to this fact, the life expectancy of patients is always reduced. Furthermore, all muscular dystrophies have in common that there is no causal therapy for them yet. It can only be attempted to increase life expectancy by delaying the muscle degradation process. Dystroglycanopathy is caused by glycosylation reactions, i.e. the linking of sugar residues to proteins, lipids or other non-sugars, not taking place properly. Glycosylated compounds perform multiple functions in the organism. The sugar residue can significantly influence the properties of the biomolecule. Among other things, glycosylated proteins form different tertiary or quaternary structures than do nonglycosylated proteins.
Causes
All dystroglycanopathies are hereditary. Usually, they involve autosomal recessive mutations. Autosomal recessive means that the affected person must have two genes with the same mutation to become ill. They receive these from both parents. Thus, both parents are not sick, but they each have a genetically altered gene. Their children have a 25 percent risk of developing dystroglycanopathy because they may be 25 percent homozygous for the mutated gene. However, there is a specific mutated gene for each disease in the group of dystroglycanopathies. For example, 15 different genes are known for muscle-eye-brain disease alone. A mutation of the FCMD gene on chromosome 9 is responsible for Fukuyama-type muscular dystrophy. Walker-Warburg syndrome, in turn, can be caused by mutations on six different genes. Similarly, the limb-girdling dystrophies 2P and 2I are each caused by an autosomal recessive mutation of a gene.
Symptoms, complaints, and signs
The common symptom of all dystroglycanopathies is an inexorably progressive muscular dystrophy that severely limits life expectancy. The accompanying symptoms depend on which disease is specifically involved. Muscle-eye-brain disease, for example, is characterized by the fact that the musculature shows reduced tension shortly after birth. There are also malformations of the eyes such as the rudimentary formation of both eyeballs, a cleft formation on the eye (coloboma) or sometimes even enlarged eyeballs. Glaucoma and retinal dysplasia may also occur, eventually leading to blindness. Furthermore, abnormalities of the face appear. Malformations of the brain are also observed. This is characterized by insufficient brain development. The formation of hydrocephalus is also possible. Patients suffer from psychomotor disorders, failure to thrive and seizures. The mouth can only be opened insufficiently due to joint contracture in the jaw joint. The life expectancy of affected individuals is between 6 and 16 years. Walker-Warburg syndrome shows similar symptoms. However, imaging techniques can distinguish its malformations in the brain from those of muscle-eye-brain disease. However, life expectancy in Walker-Warburg syndrome is as low as one year to three years.Muscular dystrophy type Fukuyama is also characterized by severe developmental disorders and brain malformations in addition to general muscle weakness. Muscle atrophy and mental retardation progress rapidly. From the age of five, there is also a rapid deterioration in motor development. Affected children usually do not live beyond the age of ten. Epileptic seizures and joint contractures often also occur in the course of the disease. All other dystroglycanopathies show similar symptoms. However, in addition to congenital muscular dystrophies with intelligence impairment, there are also congenital muscular dystrophies without intelligence impairment.
Diagnosis
The individual dystroglycanopathies can usually be distinguished only by imaging techniques such as MRI or CT. Electromyographies and muscle biopsies are also performed. Furthermore, molecular biological examinations are performed. Prenatally, a chorionic villus sampling or amniocentesis can be performed.
Complications
In most cases, dystroglycanopathy results in various disorders and complications that mainly affect the patient’s muscles. Due to the symptom, life expectancy is greatly reduced and the patient’s daily life is limited. In most patients, the muscles show a very low tension immediately after birth. This results in the formation of a cleft at the eyes. Glaucoma can also develop and, in the worst case, the patient can go completely blind. The affected person also suffers from malformations in the brain. These can negatively influence the motor function and thus also lead to a delayed mental development of the patient. There is severe retardation and muscle atrophy. If the affected person survives infancy, life expectancy is usually only about ten years. In this case, the patient suffers from epileptic seizures and reduced intelligence. As a rule, it is not possible for the affected person to cope with everyday life on his own and he is dependent on the help of parents and other people. Often, the parents are also severely psychologically burdened by the disease, resulting in depression and other psychological complaints.
When should you go to the doctor?
A doctor should be consulted for dystroglycanopathy whenever the affected person shows very low muscle tone. Usually, this complaint can be detected right after birth or in the first months of the child’s life. A cleft in the eye can also indicate dystroglycanopathy and must be examined. The children themselves complain of visual problems and also show malformations of the eyes. A visit to the doctor is also recommended if the patient shows various abnormalities in the face or if he has hydrocephalus. Complaints with food and fluid intake may also indicate the condition and need to be investigated. The initial examination may be performed by a pediatrician or general practitioner. However, further treatment requires a visit to specialists. In order to avoid disturbances in development, the child with dystroglycanopathy should be given special support. If epileptic seizures occur, an emergency physician should usually be called.
Treatment and therapy
As mentioned earlier, causal therapy is not possible for all dystroglycanopathies because they are genetic disorders. Symptomatic treatments are used to try to improve quality of life and increase life expectancy. There are differences between the individual diseases. Symptomatic treatments include physiotherapy, treatment of complications, respiratory aids and treatment of seizures. Cardiac and respiratory function must be constantly monitored in many patients. Prognosis of the disease depends on neurologic, respiratory, or cardiac complications.
Outlook and prognosis
Because dystroglycanopathy is a hereditary disease, it cannot be treated causally. Therefore, patients are always dependent on symptomatic therapy to relieve symptoms. Self-cure does not occur with this disease. Life expectancy is very limited in dystroglycanopathy if the disease is not treated. Various malformations and severe visual complaints occur.The affected persons also suffer from developmental disorders and thus also in adulthood from complications and difficulties in everyday life. Mental retardation and a reduction in intelligence occur. Dystroglycanopathy also leads to spasms in the muscles or to epileptic seizures, which can lead to the death of the patient. The motor development of the child is also significantly limited by the disease. Treatment always depends on the exact manifestation of the disease and can alleviate some symptoms. However, a complete cure is not achieved. In many cases, patients are dependent on regular examinations and permanent monitoring of bodily functions. In addition to the physical symptoms, parents or relatives often suffer from depression or other psychological upsets.
Prevention
There are no preventive measures to prevent dystroglycanopathy, as it is a genetic condition. However, most dystroglycanopathies are subject to autosomal recessive inheritance. Therefore, if there is a familial clustering of the disease, human genetic testing should be performed if there is a desire to have children. In general, there is an increased risk for offspring if the parents are related by blood and there is a history of dystroglycanopathy in the family.
Follow-up
In dystroglycanopathy, the options and measures of follow-up care are very limited. Since this is also a hereditary disease, it cannot be treated causally, but only purely causally, so that a complete cure is also usually not possible in this case. For this reason, the affected person is primarily dependent on an early diagnosis with subsequent treatment to prevent further complications or complaints. If the affected person wishes to have children, genetic counseling and testing can also be performed in case of doubt. This may prevent inheritance of the dystroglycanopathy to the children. In most cases, sufferers of this condition rely on measures of physical therapy or physiotherapy. Many of the exercises from such therapies can also be performed at home by the affected person, so that the mobility of the muscles is increased again. It is not uncommon for support and care from one’s own family or friends and acquaintances to have a positive effect on the course of dystroglycanopathy. In this context, contact with other sufferers can also be worthwhile, as this can often lead to an exchange of information.
What you can do yourself
For all dystroglycanopathies, treatment focuses on relieving symptoms. Medical measures can be supported by changes in daily life and various household and natural remedies. First of all, a comprehensive clarification of the complaints is recommended, because only in this way is a targeted and effective therapy possible. In general, the doctor will recommend physiotherapy, which can be supported by regular exercise and exercises from yoga. Accompanying aids may have to be organized. Patients who have impaired cardiac and respiratory function are often dependent on a pacemaker or need to visit the hospital regularly so that bodily functions can be checked. The exact measures to be taken depend on the nature of the disease and the severity of the symptoms. Since the prognosis for dystroglycanopathy is generally poor, psychological support is also needed. In addition, those affected need help in their daily lives, whether from relatives or an outpatient care service. Patients need to take care of these things early on so that smooth care is possible in later stages of the disease.
