Megalencephalic leukoencephalopathy (MLC) with subcortical cysts is a very rare condition that affects the white matter of the brain causing the progressive loss of physical and mental skills. The affected individuals typically present the enlarged brain (megalencephaly) evident within the first year of their life. They can also develop cysts in the brain which can grow in size and numbers. There are three types of this condition that are based on the symptoms and the genetic cause. The type 1 and 2A present different genetic causes but similar symptoms, the types 2A and 2B have the same genetic cause but the type 2B can improve after one year. This exact prevalence of this condition is not known but around 150 cases have been reported in the medical literature.
Causes
MLC develops as the result of a mutation in the gene MLC1 which produces the protein made in the brain. This protein is detected in the glial cells which protect and maintain the neurons. Research suggests the role of this protein is to control the flow of fluids into cells or the cell adhesion. The genetic mutation in the gene HEPACAM causes the types 2A and 2B. The genetic mutation of the MLC1 gene results in the deficiency of a functional MLC1 protein that results in the associated symptoms to occur. In around 5% of the cases, the genetic mutation is not identified in the MLC1 or HEPACAM gene and among these cases, the cause of the condition remains unknown. The type1 and type 2A are inherited in an autosomal recessive pattern meaning both the copies of the gene in each cell are defective. The type 2B is inherited in an autosomal dominant manner meaning a single copy of the defective gene can cause the disorder. Most cases of 2B develop as the result of de novo (new) genetic mutations that occur during the development of the reproductive cells or in the initial stages of embryonic development.
Symptoms
The infant may not present any problem during the first year of their life although the size of their head may be larger than normal. The condition can progress between the ages of two and ten showing signs of unsteadiness, the stiffness of muscle tone (dystonia) and involuntary writhing movements (athetosis). They can also have the progressive loss of mental skills over several years. Some of the children may lose the ability to walk early in life and can be a wheelchair user. Additional problems can include the epileptic seizures, behavior problems and learning difficulties. The children who have the severe loss of motor skills can also have slurring of speech and incoordination of swallowing. Minor head traumas can impair their movements which can result in coma. Among the most severe cases when the symptoms deteriorate rapidly, the life expectancy can also be significantly reduced.
Diagnosis
The diagnosis is initially based on the symptoms. The MRI brain scan can detect the abnormal enlargement of the white matter and the cysts of the brain characteristic of this disorder which may not be apparent after several years of the disorder. The genetic testing can help confirm the diagnosis although this may not be conclusive in some cases when the causative genetic mutation cannot be identified.
Treatment
There is no treatment available to stop the progression of the disorder. The treatment can help relieve some of the symptoms associated with this condition. This can include medications for seizures if and when they occur.
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