Megalencephalic leukoencephalopathy with a subcortical cyst

 A 5-year-old male child presented with an enlarged head size since birth and a history of recurrent loss of consciousness. Delayed attainment of the gross and fine motor milestones was noted.  She is academically weak and had three episodes of seizures since birth.

 The enlarged size of the head in comparison to the face is noted. There are diffuse T2 and FLAIR hyperintensity are seen in the subcortical white matter involving U fibers, periventricular and deep white matter. These areas show hypo intensity in T1-weighted images. Subcortical cystic lesions are noted in the bilateral anterior temporal lobe region. The normal signal intensity of the cortical and deep grey matter nuclei is noted. Magnetic resonance spectroscopy showed normal NAA, choline, and Cr value with NAA, creatinine ratio of 2.08, and Choline, creatinine ratio of 1.23.

Megalencephalic leukoencephalopathy with a subcortical cyst is a rare type of autosomal recessive infantile onset disorder. It is associated with a genetic mutation of the MLC1 gene [1].  It is also named as VanderKnaap disease named after a dutch physician Marjo Vander Knaap[2].

Clinically these patients present with macrocephaly developed at birth or during the first year of life. Mildly delayed motor milestones and seizure episodes may be present. Slow academic performances may be present. The patient may also present with ataxia, dysarthria, and spasticity[3].

MRI is a better imaging modality due to higher soft tissue resolution for the diagnosis. The MRI findings include diffuse white matter changes involving the cortical, subcortical white matter, and U fiber. Sparing of the deep white matter like the corpus callosum, internal capsule, and brain stem is noted. Cerebellar white matter is also spared. Subcortical cysts were seen in the anterior temporal and frontoparietal regions. Later on, subcortical cysts increase in size with atrophy of the cerebral parenchyma[3]. 

The differential diagnosis includes Canavan disease, alexander disease, and infantile-onset GM2 gangliosidosis. Canavan disease shows similar white matter findings however lacking the typical sub-cortical cyst formation. The child also shows rapid deterioration. Alexander shows the frontal predominance with thalamus and globus pallidus involvement, not seen in MLC. The extent of the disease involvement can be established based on the neurological examination, MRI imaging, physical therapy assessment, cognitive assessment, and counseling with a genetic counselor. Management of the MLC includes supportive therapy like physical therapy, speech therapy, special education, and anti-seizure medication. Prevention of secondary complications should also be considered[4].