Megaloencephalic leukoencephalopathy with subcortical cysts

Autosomal recessive disorder with onset in infancy with relatively mild early neurologic signs and symptoms in the setting of very abnormal imaging findings. Patients present during the first year of life with macrocephaly or during the second year of life with developmental delay. Over several years they develop increasing ataxia and to a lesser extent spasticity. Seizures develop in a minority of children.

There are three phenotypes caused by different gene mutations

1) MLC1 gene at 22q13.33

• 75-80% of cases

2) MLC2A caused by a homozygous mutation of HEPACAM gene at 11q24.2

• 20-25% of cases

3) MLC2B caused by heterozygous mutations of the HEPCAM gene

• Motor capabilities may normalize

On imaging

MLC1 and MLC2A

• Lack of myelin in most subcortical and deep white matter. Normal corpus callosum, internal capsules, brainstem, and occipital lobes
• Swollen subcortical white matter with enlargement of gray matter
• Anterior temporal lobe cysts which may progess to frontal lobe and parietal lobe cysts
• Increase T2 signal of the cerebellar white matter (lesser extent then cerebral white matter changes) and atrophy
• MRS shows a decrease in NAA and NAA/Cr

MLC2B

• Findings improve with time