Muscle-eye-brain disease (MEB) belongs to the disease group of congenital muscular dystrophies, which, in addition to severe functional disorders in the muscles, also show malformations in the eyes and brain. All diseases in this group are hereditary. Any form of muscle-eye-brain disease is incurable and can lead to death in childhood or adolescence.
What is Muscle Eye Brain Disease?
In the context of congenital myopathies, congenital muscular dystrophies represent the diseases with the worst prognosis. These are characterized by severe malformations of muscles, eyes and brain. The muscle-eye-brain disease is closely related to the so-called Walker-Warburg syndrome as a congenital muscular dystrophy. In contrast to Walker-Warburg syndrome, however, MEB is somewhat milder. See electronicsmatter for Hyperhydration Definition.
In addition to the numerous muscular dystrophies, both diseases also show pathological changes in the eyes and brain. In Walker-Warburg syndrome, there is a faulty brain structure with gaps in the skull (encephalocele) through which parts of the brain can protrude. This is not the case with MEB, so the encephalocele is the distinguishing feature of both diseases.
For this reason, life expectancy in Walker-Warburg syndrome is significantly lower than in muscle-eye-brain disease. Here it is only two years, while a patient with the muscle-eye-brain disease can live between 6 and 16 years, depending on the course. Both diseases are also caused by mutations in the same genes.
Mainly six genes are responsible for it. The occurrence of congenital muscular dystrophies is geographically very inconsistent. Muscle-eye-brain disease is being observed more and more in Finland. Overall estimates for all congenital muscular dystrophies are 1 in 20,000 newborns.
Causes
Different genetic defects in mainly six different genes are held responsible for the causes of MEB. These are the genes for the enzymes POMT1, POMT2, POMGNT1, Fukutin (FKTN), FKRP or LARGE1. The respective encoded enzymes support the glycosylation of membrane proteins. POMT1 and POMT2 are protein O-mannosyltransferases.
They are responsible for transferring mannose to the membrane proteins of muscle, eye and brain cells. There the mannose molecules are glycosidically bonded to the functional side groups of the amino acids serine or threonine within the protein chain. When the sugar residue is attached to the protein chain, the properties of the protein change. The individual protein chains of the extracellular matrix and cytoskeleton are more closely linked.
When this process is disrupted, muscle-eye-brain disease can develop as a result. The other enzymes mentioned also catalyze individual reaction steps in the glycosylation of proteins, which also contribute to the crosslinking of extracellular matrix with the cytoskeleton. All forms of muscle-eye-brain disease are inherited in an autosomal recessive manner.
People with only one defective gene do not get sick. However, if both parents each have a mutated gene, their offspring have a 25 percent chance of developing MEB. This is the case when the child inherits the diseased gene from both parents.
Symptoms, Ailments & Signs
Muscle-eye-brain disease is characterized by a variety of serious symptoms and abnormalities affecting the muscles, eyes, and brain. The disease appears shortly after birth. The muscles are in a low state of tension (tonus). There is constant muscle weakness.
The affected children have difficulty breastfeeding because they are very weak. They also have either small eyeballs (microphthalmia), clefts in the eyes or greatly enlarged eyeballs. In addition, there is malformation of the retina and the development of glaucoma. In addition, the malformations of the eyes can lead to blindness.
The brain is also often malformed. The cerebral convolutions may be absent entirely or have an unusual structure. The optic nerve is often insufficiently developed. Underdevelopment of the cerebellum is also frequently observed. Psychomotor limitations, failure to thrive, convulsions, and mental retardation occur. Sometimes a so-called hydrocephalus (water on the head) occurs, which, however, is usually not very severe.
The mouth can only be opened to a limited extent because the jaw muscles contract. The muscle and eye weakness worsens very quickly. This leads to a developmental delay in the child. Motor skills also deteriorate. Cramps are becoming more frequent. The disease is incurable and ends fatally at the latest in adolescence.
Diagnosis & course of disease
To diagnose MEB, a family medical history is first taken. Here it is determined whether this disease has already occurred in the family. Genetic tests can be used to determine which gene is responsible for the disease. Other tests include brain ultrasound, eye inspection, and blood creatine kinase levels.
When should you go to the doctor?
In the case of hereditary muscle-eye-brain disease, the first contact with the doctor is often immediately after birth. The severity of the genetic damage is so serious that those affected usually do not survive for long. A maximum age of 16 years is achievable.
Why muscle-eye-brain disease is particularly common in Finland has been a mystery. Ideally, it is known that both parents have corresponding genetic predispositions. In this case, the doctor’s visit could serve as an indication for an abortion. A subsequent sterilization measure by the parents would also have to be discussed.
Such muscular dystrophies caused by gene mutations cause severe symptoms right at the beginning of life. They also leave visible damage to the brain and eyes. This consequential damage is usually noticed immediately, rarely later in a child’s life. If the symptoms for the correct diagnosis are not clarified immediately after birth, a visit to the doctor because of the unusual weakness of the newborn is usually made within the next few months.
The appearance of newborns is often indicative of muscle-eye-brain disease. A visit to the doctor is therefore unavoidable. All further visits to the doctor result in an attempt to alleviate the symptoms. More than symptomatic treatment, such as artificial respiration or artificial feeding of children with the rarely occurring muscle-eye-brain disease, is currently not possible.
Treatment & Therapy
Unfortunately, there is no causal therapy for MEB. However, this applies to all congenital muscular dystrophies. These diseases are very rare. Accordingly, there is little experience with their treatment. Only symptomatic treatments to improve quality of life and prolong life are currently available.
In very severe cases, tube feeding or ventilation is sometimes necessary due to muscle weakness. The most important measure, however, is the best possible support for the child within the framework of the existing possibilities.
Complications
As a rule, muscle-eye-brain disease causes various symptoms and malformations, which mainly affect the patient’s muscles, eyes and brain. Due to these malformations, the everyday life of those affected is significantly restricted and the quality of life is greatly reduced. Furthermore, life expectancy is also significantly reduced by this disease, so that the patient usually dies in adolescence.
As a result, family members and parents in particular experience psychological problems and depression. Those affected suffer from complete blindness and muscle weakness. As a result, the muscle-eye-brain disease causes considerable limitations in everyday life, so that in most cases the patients are dependent on the help of other people.
The symptoms also lead to mental retardation and, in general, to severe developmental delays. Those affected can also suffer from severe cramps. A causal treatment of muscle-eye-brain disease is not possible. However, the symptoms can be alleviated so that everyday life becomes bearable for the patient. In the last stage of life, in most cases, artificial nutrition and artificial respiration are also necessary.
Outlook & Forecast
Muscle-eye-brain disease is one of the muscular dystrophies with the worst prognosis. The prospect of an improvement in the state of health is only given with early treatment. Irrespective of the time of treatment, there is a risk of treatment failure. The consequence of a failed therapy can be a re-infection. The myopia of the affected children progresses rapidly.
After just a few months of life, a significant deterioration in vision can be observed. Motor skills deteriorate considerably by the time the child is five years old at the latest. This is accompanied by spasms and contractures, which further worsen the prognosis. Life expectancy is greatly reduced. Depending on the course of the disease, affected children reach the age of six to sixteen.
The quality of life decreases continuously. However, well-being can be improved through comprehensive symptomatic therapy, such as the administration of painkillers and physiotherapeutic measures. The specialist doctor responsible makes the prognosis with regard to the symptoms identified and the constitution of the child. The overall prognosis is poor. The rare disease also represents a great burden for the family of the child. A therapeutic work-up is usually necessary. In general, muscle-eye-brain disease is a serious condition that takes a heavy toll on those affected, both physically and mentally.
Prevention
MEB is a genetic disease. Therefore, there can be no preventive measures to prevent them. However, if cases of illness are known within the family or relatives, the risks of the disease being passed on to the offspring can be assessed by means of human genetic counseling. If both parents are carriers of the mutated gene, the probability of MEB in the offspring is already 25 percent.
Aftercare
In the case of muscle-eye-brain disease, follow-up care is usually relatively difficult, and in many cases no special measures are available to the person affected. The sufferer should therefore consult a doctor at the first signs and symptoms of this disease, so that further complications or symptoms can be prevented.
Since this is a genetic disease, complete healing cannot usually take place. If the person concerned wants to have children, they should definitely have a genetic test and counseling carried out in order to prevent the muscle-eye-brain disease from reoccurring.
The symptoms themselves can be alleviated by some surgical interventions. The affected person should rest after such an operation and take care of his body. Efforts or stressful and physical activities should be avoided. Likewise, the help and care of one’s own family is often very important.
Psychological support is also important to prevent depression and other mental health problems. Further follow-up measures are not available to patients with muscle-eye-brain disease because the disease itself significantly reduces life expectancy.
You can do that yourself
Due to the severity of the disorders, muscle-eye-brain disease already leads to premature death in childhood or in adolescents. The means and possibilities of the disease are minimal for the person affected. There are no techniques or methods that bring about a cure or that lead to the achievement of average life expectancy.
Due to the course of the disease, the focus should be on improving the quality of life. The relatives and people from the social environment should inform themselves comprehensively about the disease and its consequences. A change in lifestyle is taking place, especially for family members. Despite all the adversities and the poor prognosis, an optimistic and positive attitude to life helps to cope with the daily challenges. The leisure activities are to be aligned with the wishes and needs of all those involved. stress, arguments and conflicts should be avoided if possible. In the decision-making process for enhancing the well-being of the patient, unity and cohesion among the relatives are essential. You should act in the best interests of the child and avoid selfish patterns of behavior.
Since the illness represents a strong emotional burden, the use of psychological care for the relatives is advisable. An exchange in self-help groups can be perceived as strengthening, since tips and mutual support are a central focus of the contact.
