Megalencephalic Leukodystrophy with subcortical cysts
MLC; Van der Knapp syndrome; vacuolating leukodystrophy with subcortical cysts; megalencephaly-cystic leukodystrophy syndrome
Inheritance:
Type 1 and 2A: Autosomal recessive Inheritance from both parents will result in the disease. Type 2B: Autosomal dominant Inheritance from one parent will result in the disease
Age range at onset:
Neonatal or within the first year
Specialists you may see:
Symptoms
MLC Type 1 and Type 2A have almost identical symptoms (with different causes). MLC Type 2B has similar symptoms but these often begin to improve after one year.
Megalencephaly is typically evident at birth or within the first year, and individuals may develop cysts in the brain. Spasticity and ataxia are common, affecting walking ability in some but not all those affected. Minor head trauma may worsen movement difficulties and can lead to coma. Dystonia, swallowing difficulties, dysarthria and athetosis are common. Most will suffer from seizures, but will not experience severe intellectual disability.
Cause
In around 75% of cases (type 1), MLC is caused by mutations in the MLC1 gene. This gene creates a protein found primarily in the brain, at the junctions between some types of cell. It is unknown how this leads to impairment of brain function.
MLC can also be caused by mutations of the HEPACAM gene; this results in MLC type 2A or 2B. The HEPACAM gene creates a different protein which is important to cell junctions in the brain.
Around 5% of those with this condition do not have mutations in the MLC1 gene or the HEPACAM gene. The cause of MLC in these people is unclear.