Megalencephalic Leukoencephalopathy with Subcortical Cysts (MLC). Van der Knaap disease.
Incidence
MLC is inherited in an autosomal recessive manner. MLC is a rare disease with a low carrier rate except for specific populations. In many patients with MLC, the parents are consanguineous. Common in India. Also seen in Texas.
Clinical Characteristics
Its main clinical characteristics are infantile-onset macrocephaly, progressive motor dysfunction with delayed onset of mental retardation with mild clinical course, imaging findings typical of leukodystrophic abnormalities and subcortical cysts are the distinctive features of this disease. Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is characterized by early-onset macrocephaly, often in combination with mild gross motor developmental delay and incidental seizures; gradual onset of ataxia, spasticity, and sometimes extrapyramidal findings; and usually late onset of mild mental deterioration. Macrocephaly, present in all patients, is present at birth or, more frequently, develops during the first year of life. The degree of macrocephaly is variable and can be as much as 4-6 SD above the mean in some patients. After the first year of life, head growth rate normalizes and growth follows a line parallel to the 98th percentile, usually several centimeters above it. Almost all patients have epilepsy from an early age. Initial mental and motor development is normal in most cases. Walking is often unstable, followed by ataxia of the trunk and extremities, then minor signs of pyramidal dysfunction and brisk deep tendon stretch reflexes. Mental deterioration is late and mild. Severity ranges from independent walking for a few years only to independent walking in the fifth decade. Some patients have died in their teens or twenties, but others are alive in their forties. Some patients have a more benign clinical course. Even as teenagers, they only have macrocephaly. Some patients still walk independently in their forties. As the disease has been known for only a relatively short time, little information is available about average life span. Some patients have died in their teens or twenties, but others are alive in their forties.
Precipitants
Minor head trauma may induce temporary deterioration in some patients, most often observed as seizures, prolonged unconsciousness, or acute motor deterioration with gradual improvement.
Provocation Tests
no
Diagnostic Procedures
The diagnosis of megalencephalic leukoencephalopathy with subcortical cysts (MLC) can be made with confidence in patients with typical clinical findings and characteristic abnormalities on cranial magnetic resonance imaging (MRI). The diagnosis of MLC is established in patients with typical clinical findings and characteristic abnormalities in cranial MRI. Mutations in the MLC1 gene at 22qter, found by sequence analysis in approximately 60-70% of patients with MLC, can be used for confirmation of the diagnosis. Such testing is clinically available. Mutations in the MLC1 gene have been found in approximately 60-70% of patients with MLC. Evidence exists for at least one other gene for MLC. Thus, finding mutations in MLC1 confirms the diagnosis of MLC, but absence of mutations does not exclude the diagnosis when the clinical and MRI findings are characteristic. Routine laboratory tests, including cerebrospinal fluid analysis, are normal.