7 months old male child presented with recurrent seizure and delayed developmental milestones. The child has macrocephaly with head circumference 53cm ( more than 97 percentile).
a) Axial T2- Megalencephaly with with diffuse T2- weighted hyperintensity in cerebral white matter (involvement of subcortical U- fibres) with sparing of cerebellum and posterior fossa
b) Axial T2 FLAIR- diffuse symmetrical hyperintensity in white matter
c) Axial T1 FLAIR- diffuse symmetrical hypointensity on white matter
d) Coronal T2- bilateral subcortical cysts of CSF intensity affecting the anterior temporal regions
Megalencephalic leukoencephalopathy with subcortical cyst is also called Van der Knaap disease. It is a rare inherited neurological disease with autosomal recessive pattern of inheritance. The gene involved is MLC1 gene at chromosome 22q.
Patients usually present with megalencephaly, delayed developmental milestones and seizure in childhood. Further progression of neurological functions in terms of ataxia, spasticity, dysarthria and extrapyramidal symptoms may occur. It is more prevalent in Aggarwal community in India, also called Aggarwal’s disease.
MRI is the most preferred imaging modality with the following features:
Eventually, there is cerebral atrophy and progressive increase in the size of the subcortical cysts. Treatment is symptomatic with antiepileptic drugs to control the seizure. Physical therapy can be tried to improve motor function.
Take-Home Message / Teaching Points
MRI shows very characteristic findings; however, it can not predict the future progression and outcome of the disease. It can be diagnosed antenatally by chorionic villous sampling and amniocentesis. Prognosis of the disease remains poor.
 Singhal BS, Gursahani RD, Udani VP, Biniwale AA. Megalencephalic leukodystrophy in an Asian Indian ethnic group. Pediatr Neurol. 1996 May;14(4):291-6. doi: 10.1016/0887-8994(96)00048-3. PMID: 8805171.
 Kumar MK, Singh BB. Megalencephalic leukoencephalopathy with subcortical cysts in all three siblings of a non-Aggarwal Indian family. Ann Indian Acad Neurol. 2012 Jul;15(3):214-7. doi: 10.4103/0972-2327.99723. PMID: 22919198; PMCID: PMC3424803.
 Gorospe JR, Singhal BS, Kainu T, Wu F, Stephan D, Trent J, Hoffman EP, Naidu S. Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation. Neurology. 2004 Mar 23;62(6):878-82. doi: 10.1212/01.wnl.0000115106.88813.5b. PMID: 15037685.
 Türkyılmaz, A, Ünver, O, Ekinci, G and Türkdoğan, D. "A Novel splice-site mutation on the MLC1 gene leading to exon 9 skipping and megalencephalic leukoencephalopathy with subcortical cysts in a Turkish patient" Balkan Journal of Medical Genetics, vol.22, no.2, 2019, pp.89-92. https://doi.org/10.2478/bjmg-2019-0019
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