Muscle-eye-brain disease (MEB) belongs to the disease group of congenital muscular dystrophies, which in addition to severe dysfunction in the muscles also have malformations in the eyes and brain. All diseases of this group are hereditary. Any forms of muscle-eye-brain disease are incurable and lead to death in childhood or adolescence.
What is muscle-eye-brain disease?
Within the congenital myopathies, congenital muscular dystrophies represent the diseases with the worst prognosis. These are characterized by severe malformations of the muscles, eyes, and brain. As a congenital muscular dystrophy, muscle-eye-brain disease is closely related to the so-called Walker-Warburg syndrome. In contrast to Walker-Warburg syndrome, however, MEB runs a somewhat milder course. In addition to the numerous muscular dystrophies, both diseases show pathological changes in the eyes and brain. In Walker-Warburg syndrome, there is a defective brain anatomy with gaps in the skull (encephalocele) through which parts of the brain can leak out. This is not the case in MEB, so that the encephalocele is the distinguishing feature of both diseases. For this reason, life expectancy is significantly lower in Walker-Warburg syndrome as opposed to muscle-eye-brain disease. Here, it is only two years, whereas a patient with 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. The occurrence of congenital muscular dystrophies is geographically very uneven. For example, muscle-eye-brain disease is more commonly observed in Finland. Overall, estimates for total congenital muscular dystrophies are 1 in 20,000 newborns.
Causes
The causes of MEB are thought to be various genetic defects in mainly six different genes. These are the genes encoding the enzymes POMT1, POMT2, POMGNT1, fucutin (FKTN), FKRP, or LARGE1. The respective encoded enzymes support glycosylation of membrane proteins. POMT1 and POMT2 are protein O-mannosyltransferases. They are responsible for the transfer of mannose to the membrane proteins of muscle, eye and brain cells. There, glycosidic binding of the mannose molecules to the functional side groups of the amino acids serine or threonine within the protein chain occurs. With the linkage of the sugar residue to the protein chain, the properties of the protein change. The individual protein chains of extracellular matrix and cytoskeleton become more interconnected. If this process is disturbed, muscle-eye-brain disease may develop as a consequence. The other enzymes mentioned also each catalyze individual reaction steps in the glycosylation of proteins, which likewise contribute to the cross-linking of extracellular matrix with the cytoskeleton. All forms of muscle-eye-brain disease are inherited in an autosomal recessive manner. Individuals with only one defective gene do not develop the disease. 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 each of the two parents.
Symptoms, symptoms, and signs
Muscle-eye-brain disease is characterized by a variety of severe symptoms and deformities of the muscles, eyes, and brain. The disease appears shortly after birth. The muscles show a low state of tension (tone). There is permanent muscle weakness. Affected children have difficulty breastfeeding because they are very weak. Furthermore, they 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 completely absent or unusually structured. The optic nerve is often insufficiently developed. Underdevelopment of the cerebellum is also frequently observed. Psychomotor impairments, failure to thrive, convulsions and mental retardation occur. Sometimes a so-called hydrocephalus (water head) occurs, which, however, is usually not very pronounced.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 of the child. Motor skills also deteriorate. Convulsions occur more and more frequently. The disease is incurable and ends fatally in adolescence at the latest.
Diagnosis and course of the disease
To diagnose MEB, a family medical history is first taken. Here, it is determined whether this disease has already occurred in the relatives. Genetic testing can be used to determine which gene is responsible for the disease. Other tests include ultrasound examinations of the brain, eye inspection, and determination of creatine kinase in the blood.
When should you see a doctor?
For hereditary muscle-eye-brain disease, the first contact with a doctor is often immediately after birth. The severity of the genetically caused damage is so severe that affected individuals usually do not have a long survival period. A maximum age of 16 years is achievable. Why the muscle-eye-brain disease is particularly common in Finland is still a mystery. Ideally, both parents are known to have corresponding genetic predispositions. In this case, the doctor’s visit could serve as an abortion indication. Subsequent sterilization of the parents could also be discussed. Such muscular dystrophies caused by genetic mutations cause severe symptoms right at the beginning of life. They also leave detectable damage to the brain and eyes. These consequential damages are usually noticed immediately, rarely a little later in a child’s life. If the clarification of the symptoms for the correct diagnosis is not made immediately after birth, it is usually made within the next few months by a visit to the doctor because of unusual weakness of the newborn. The appearance of the newborn often already indicates the muscle-eye-brain disease. So a visit to the doctor can hardly be avoided. All further visits to the doctor result in an attempt to alleviate the symptoms. More than symptomatic treatment, such as ventilatory support or artificial feeding for infants with the rare muscle-eye-brain disease, is currently not possible.
Treatment and therapy
Unfortunately, there is no causal therapy for MEB. However, this is true for all congenital muscular dystrophies. These disorders occur very rarely. Accordingly, little experience is available on 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. However, the most important measure is to provide the best possible support for the child within the existing possibilities.
Complications
As a rule, muscle-eye-brain disease results in various complaints and malformations that occur mainly in the muscles, eyes, and brain of the patient. Due to these malformations, the daily life of the affected person is significantly limited and there is a greatly reduced quality of life. Furthermore, life expectancy is also significantly reduced by this disease, so that the patient usually dies in adolescence. As a result, psychological complaints and depression occur, especially among the relatives and parents. Those affected suffer from complete blindness and muscle weakness. As a result, the muscle-eye-brain disease leads to considerable limitations in everyday life, so that in most cases the patients are dependent on the help of other people. Likewise, the symptoms also lead to mental retardation and generally to severe developmental delays. Likewise, affected individuals may 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, artificial nutrition and artificial respiration are also necessary in most cases.
Outlook and prognosis
Muscle-eye-brain disease is among the muscular dystrophies with the worst prognosis. There is a prospect of improvement in health only with early treatment.Regardless of the time of treatment, there is a risk of treatment failure. The consequence of a failed therapy can be a renewed infection. The myopia of affected children progresses rapidly. A marked deterioration of vision can be observed after only a few months of life. Motor function deteriorates significantly by the child’s fifth year of life at the latest. Accompanying spasticity and contractures occur, 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 by comprehensive symptomatic therapy, such as the administration of painkillers and physiotherapeutic measures. The prognosis is determined by the specialist in charge in view of the symptoms observed and the child’s constitution. The prognosis is therefore poor overall. The rare disease is also a great burden for the child’s relatives. In most cases, therapeutic reprocessing is necessary. In general, muscle-eye-brain disease is a severe condition that places a heavy physical and psychological burden on those affected.
Prevention
MEB is a genetic disease. Therefore, there can be no preventive measures to prevent it. However, if cases of the disease are known within the family or relatives, human genetic counseling can be used to assess the risks of passing the disease on to offspring. If both parents are carriers of the mutated gene, the probability of MEB in the offspring is already 25 percent.
Follow-up
In muscle-eye-brain disease, follow-up care usually proves to be relatively difficult, with no special measures at all available to the affected person in many cases. The affected person should therefore consult a doctor at the first signs and symptoms of this disease so that further complications or discomfort can be prevented. Since this is a genetic disease, a complete cure is usually not possible. Therefore, if the affected person wishes to have a child, he or she should in any case have a genetic examination and counseling to prevent a recurrence of the muscle-eye-brain disease. The symptoms themselves can be alleviated by some surgical interventions. The affected person should rest and take care of his body after such an operation. They should refrain from exertion or from stressful and physical activities. Likewise, help and care from one’s family is often very important. Psychological support is also important to prevent depression and other psychological complaints. Other measures of aftercare are not available to the patient with muscle-eye-brain disease, as the disease itself significantly limits life expectancy.
Here’s what you can do yourself
Muscle-eye-brain disease leads to premature death in childhood or adolescents due to the severity of the disorders. The remedies and options for the disease are minimal for the affected person. There are no techniques or methods that can bring about a cure or lead to the achievement of average life expectancy. Because of the course of the disease, the focus must be on improving the quality of life. Relatives and people from the social environment should be fully informed about the disease and its consequences. A change in lifestyle takes place, especially for the family members. Despite all adversities and the poor prognosis, an optimistic as well as positive attitude towards life helps to cope with the daily challenges. Leisure activities should be arranged according to the wishes and needs of all involved. Stress, quarrels and conflicts should be avoided if possible. In the decision-making process for strengthening the well-being of the patient, unity and cohesion of the relatives are essential. They should act in the best interest of the child and avoid selfish behaviors. Since the disease represents a strong emotional burden, the use of psychological support 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.
