Objective:

To present a 20 year follow-up case of a patient with Megalencephalic leukoencephalopathy
with subcortical cysts (MLC) with an unusually severe and progressive clinical course.

Background:

Megalencephalic leukodystrophy with subcortical cysts (MLC), also known as van der Knapp
leukodystrophy, is a rare autosomal recessive disease reported to occur in approximately 1 in
1,000,000 individuals. It usually presents in early childhood with macrocephaly, motor delay,
and seizures. It is characterized by progressive but often relatively slow neurological decline
compared to other leukodystrophies.

Design/Methods:

We describe a case of a 23 year old patient who has severe, progressive MLC disorder, resulting
in severe intellectual disability, spastic quadraplegia and relatively well controlled epilepsy with
accompanying literature review detailing the clinical course, diagnostic process, and genetic
findings associated with this disorder.

Results:

MRI Brain was consistent with typical findings of MLC and showed diffused white matter
disease and a large bilateral anterior temporal pole parenchymal cysts. Genetic test confirmed
MLC1 mutation with mutation in (heterozygous) (c.206 > T p.Ser69Leu) and Partial Deletion
(Exons 4-5). Over the course of two decades, the patient progressed from mild developmental
delay and dystonia to severe intellectual disability, generalized dystonia, and spastic
quadriplegia, with relatively well-controlled epilepsy.

Conclusions:

This case highlights an unusually severe phenotype associated with MLC1 mutations.
Unlike the typical slowly progressive course of MLC, this patient developed profound motor
disability and severe cognitive decline. Patient also has infrequent generalized or focal seizures
throughout his early childhood and has been well-controlled for more than 10 years on
Levetiracetam.