Dystroglycanopathies are hereditary muscular dystrophies. It is a group of muscle diseases with different symptoms, but all of which arise from disorders of certain glycosylations. There are currently no causal treatment options for all dystroglycanopathies.
What are dystroglycanopathies?
According to percomputer, dystroglycanopathies are hereditary muscular dystrophies that are based on metabolic disorders of glycosylation reactions. They are very rare diseases with muscle weakness and various other physical or mental impairments. Life expectancy is usually not very high.
Dystroglycanopathy is a collective term for a heterogeneous group of very rare muscular dystrophies. Some diseases have only been described once so far. Dystroglycanopathies include muscle-eye-brain disease, Fukuyama type muscular dystrophy or Walker-Warburg syndrome.
This group also includes very rare forms of girdle dystrophy such as girdle dystrophy 2P or girdle dystrophy 2I. Muscular dystrophies are diseases that are always associated with increasing muscle weakness and muscle wasting. In all muscular dystrophies, muscle breakdown is irreversible. Due to this fact, the life expectancy of patients is always reduced.
What is more, all muscular dystrophies have in common that there is as yet no causal therapy for them. One can only try to increase the life expectancy by delaying the muscle breakdown process. Dystroglycanopathy is caused by the fact that glycosylation reactions, i.e. the linking of sugar residues to proteins, lipids or other non-sugars, do not take place properly.
Glycosylated compounds have a variety of 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 non-glycosylated proteins.
Causes
All dystroglycanopathies are hereditary. Usually they are autosomal recessive mutations. Autosomal recessive means that the affected person must have two genes that are mutated in the same way in order to become ill. She receives this from both parents. Both parents are not sick, but they each have a genetically modified gene.
Your children have a 25 percent risk of dystroglycanopathy because they can be 25 percent homozygous for the mutated gene. However, there is a special mutated gene for each disease from the group of dystroglycanopathies. 15 different genes are known for muscle-eye-brain disease alone.
A mutation in the FCMD gene on chromosome 9 is responsible for the Fukuyama type muscular dystrophy. Walker-Warburg syndrome, in turn, can be caused by mutations in six different genes. Girdle dystrophies 2P and 2I are each caused by an autosomal recessive mutation of a gene.
Symptoms, ailments & signs
The common symptom of all dystroglycanopathies is an unstoppable progressive muscular dystrophy, which severely limits life expectancy. The accompanying symptoms depend on the specific disease.
Muscle-eye-brain disease is characterized by the fact that the muscles show reduced tension shortly after birth. There are also malformations of the eyes such as the rudimentary formation of both eyeballs, a gap in the eye (coloboma) or sometimes even enlarged eyeballs. It can also be a glaucoma and retinal dysplasia occur that will eventually lead to blindness.
There are also abnormalities on the face. Malformations of the brain are also observed. This is characterized by insufficient brain development. The formation of a water head is also possible. The patients suffer from psychomotor disorders, failure to thrive, and seizures. The mouth can only be opened insufficiently due to joint contractures in the jaw joint.
The life expectancy of those affected is between 6 and 16 years. Walker-Warburg syndrome shows similar symptoms. However, imaging methods can be used to differentiate its malformations in the brain from those of the muscle-eye-brain disease. However, life expectancy in Walker-Warburg syndrome is only one to three years.
Fukuyama type muscular dystrophy is also characterized by severe developmental disorders and brain malformations in addition to general muscle weakness. Muscle wasting and mental retardation progress rapidly. From the age of five there is also a rapid deterioration in motor development.
The affected children usually do not get older than ten years. The disease often leads to epileptic seizures and joint contractures. All other dystroglycanopathies show similar symptoms. However, in addition to congenital muscular dystrophies with intellectual disabilities, there are also congenital muscular dystrophies without intellectual disabilities.
Diagnosis
The individual dystroglycanopathies can usually only be differentiated by imaging methods such as MRI or CT. In addition Elektromyografien and muscle biopsies performed. Molecular biological investigations are also carried out. A chorionic villus sampling or amniocentesis can be performed prenatally.
Complications
In most cases, dystroglycanopathy is associated with various disorders and complications that mainly affect the patient’s muscles. As a result of the symptom, life expectancy is greatly reduced and the patient’s everyday life is restricted. In most patients, the muscles show very little tension immediately after birth.
This leads to the formation of a gap in the eyes. This can also lead to glaucoma and, in the worst case, completely blind the patient. The person concerned also suffers from malformations in the brain. These can negatively affect the motor skills and thus lead to a delayed mental development of the patient.
There is severe retardation and muscle wasting. If the affected person survives infancy, life expectancy is usually only around ten years. The patient suffers from epileptic seizures and decreased intelligence.
As a rule, it is not possible for those affected to cope with everyday life on their own and they have to rely on the help of their parents and other people. Often the parents are mentally stressed by the illness, which leads to depression and other psychological complaints.
When should you go to the doctor?
A doctor should always be consulted for dystroglycanopathy if the person concerned shows very low muscle tension. As a rule, this complaint can be recognized immediately after the birth or in the first few months of the child’s life. A crack 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 on the face or if he has a head of water. Discomfort when taking food and fluids can also indicate the disease and must be investigated.
The first exam can be done by a pediatrician or a general practitioner. For further treatment, however, a visit from a specialist is necessary. In order to avoid disturbances in development, the child should be given special support in the case of dystroglycanopathy. If an epileptic seizure occurs, an emergency doctor should usually be called.
Treatment & Therapy
As already mentioned, a causal therapy is not possible with all dystroglycanopathies, because they are genetically determined diseases. As part of symptomatic treatments, attempts are made to improve the quality of life and increase life expectancy. There are differences between the individual diseases.
Among the symptomatic therapies counts physiotherapy, treatment of complications, breathing aids and treatment of seizures. The heart and respiratory functions must be constantly monitored in many patients. The prognosis of the disease depends on the neurological, respiratory, or cardiac complications.
Outlook & forecast
Since dystroglycanopathy is a hereditary disease, the cause cannot be treated. The patients are therefore always dependent on symptomatic therapy that can alleviate the symptoms. Self-healing does not occur with this disease.
Life expectancy in dystroglycanopathy is very limited if the disease is not treated. Various malformations and severe visual problems occur. Those affected also suffer from developmental disorders and thus also in adulthood from complications and difficulties in everyday life.
There is mental retardation and a reduction in intelligence. Dystroglycanopathy also leads to cramps in the muscles or to epileptic seizures, which can lead to the death of the patient. The child’s motor development is also significantly restricted by the disease.
The treatment always depends on the exact severity of the disease and can alleviate some symptoms. However, a complete cure is not achieved. In many cases, patients depend on regular examinations and constant monitoring of body functions. In addition to the physical complaints, the parents or relatives often suffer from depression or other psychological disorders.
Prevention
There are no preventive measures to prevent dystroglycanopathy because it is a genetic disease. However, most dystroglycanopathies are inherited as an autosomal recessive trait. Therefore, if there is a familial accumulation of the disease, human genetic examinations should be carried out if there is a desire to have children. In general, there is an increased risk for the offspring if the parents are blood relatives and dystroglycanopathy has already occurred in the relatives.
Aftercare
With dystroglycanopathy, the possibilities 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 usually not possible. For this reason, the person concerned is primarily dependent on an early diagnosis with subsequent treatment so that there are no further complications or complaints.
If the person concerned wishes to have children, genetic counseling and testing can also be carried out in case of doubt. This may prevent dystroglycanopathy from being passed on to children. In most cases, those affected with this disease are dependent on measures of physiotherapy or physiotherapy.
Many of the exercises from such therapies can also be performed at home by the person concerned, so that the mobility of the muscles is increased again. It is not uncommon for the support and care provided by one’s own family or friends and acquaintances to have a positive effect on the course of dystroglycanopathy. Contact with other affected persons can also be worthwhile, as this can often lead to an exchange of information.
You can do that yourself
For all dystroglycanopathies, treatment focuses on relieving symptoms. The medical measures can be supported by changes in daily life and various resources from the household and nature.
First of all, a comprehensive clarification of the symptoms is recommended, because this is the only way to achieve targeted and effective therapy. In general, the doctor will recommend physiotherapy, which can be supported by regular exercise and exercises from yoga. In addition, aids may have to be organized.
Patients with impaired cardiac and respiratory function often need a pacemaker or have to visit the hospital regularly so that their body functions can be checked. The exact measures to be taken depend on the type of illness and the severity of the symptoms.
Since the prognosis for dystroglycanopathy is generally poor, psychological support is also required. In addition, those affected need help in everyday life, be it from relatives or from an outpatient care service. Patients need to address these issues early on so that proper care can be provided in the later stages of the disease.
