Van der Knaap Syndrome (Vacuolating Leukodystrophy with Subcortical Cysts or MLC)
Vacuolating leukoencephalopathy with subcortical cysts (VLE) is genetically determined leukoencephalopathy with widespread swelling and sponginess of the cerebral white matter and formation of subcortical cysts, always in the anterior-temporal area, often also in the frontal and parietal areas.
VLE is clinically a homogenous disease that does not have early and late-onset variance, although there is a variation in severity of the disease. All patients develop a macrocephaly during the first year of life and some patients already have it at birth. Typically, early development is normal or only mildly delayed. Independent walking is often delayed and unstable. Usually, a CT scan or MRI of the brain is obtained in this stage under the suspicion of slowly progressive hydrocephalus. The scans then show a diffuse abnormality of the cerebral white matter, which also is swollen. Because of that, the overlying cortex is stretched and gyri are weakened. MRI always shows subcortical cysts in the anterior-temporal area, often also in the frontoparietal area. This MRI picture should lead to the correct diagnosis.
During the first years of life, children with VLE usually have a normal or close to normal function. From the age of 4 to 5 years onwards, most children develop a slowly progressive cerebellar ataxia. Because of the ataxia speech becomes unclear too. From the age of late primary school onwards, mental slowing is noted and learning problems develop, although mental capacities remain relatively better intact than motor capacities. Most children have infrequent epileptic seizures, which can be easily controlled with anti-epileptic medication.
There are more severe variants. In some children, early development is already seriously delayed. Some children never achieve independent walking or lose it within a few years. Sometimes the epilepsy is more serious. However, there are also milder variants in which independent walking is maintained for several decades. In some patients, mental capacities remain intact for a long time.
Further information can be obtained from:
Van der Knaap Syndrome (Vacuolating Leukodystrophy with Subcortical Cysts or MLC) [external]