CASE 18572 Published on 31.05.2024

Megalencephalic leukoencephalopathy



Case Type

Clinical Case


Rishabh, Priyanka P. Baishya, Parul Dutta, Bhaskar Das

Gauhati Medical College and Hospital, Guwahati, Assam, India


8 years, male

Area of Interest CNS, Neuroradiology brain, Paediatric ; Imaging Technique MR
Clinical History

The patient (8-year-old, male) had a presentation with increased head size and a history of delayed development of milestones. There were three episodes of seizure in the last year, with recent complaints of ataxia for 3 weeks. Birth history was normal, with no history of birth asphyxia or antenatal infections.

Imaging Findings

MR brain revealed diffuse T2 and FLAIR weighted imaging hyperintense signals in bilateral periventricular and subcortical white matter. There was a sparing of the bilateral thalamo-capsuloganglionic region noted. Subcortical cysts were noted in anterior temporal regions on both sides. The head size was increased for ages, suggestive of macrocephaly. The cerebellum and the brainstem did not show any significant findings. On DWI, no diffusion restriction was noted. In the post-contrast study, there is no abnormal enhancement seen.


Megalencephalic leukoencephalopathy (MLC) with subcortical cysts was first noted by Van der Knaap and colleagues and was put in a classification as a rare disorder. MLC exhibits a heightened occurrence in populations with increased consanguinous marriage. This autosomal recessive condition arises from mutations in the MLC1 gene, located at chr22qter. Notably, most of the cases in India are observed within the people of the Agrawal community [1,2].

MLC is recognised for presenting non-specific clinical signs amidst markedly abnormal magnetic resonance (MR) findings. Macrocephaly is evident clinically. Early developmental stages are typically within normal limits or show minimal delay. Motor actions could be affected by ataxia or spasticity, evident in early phases.

Typically, MR findings play a diagnostic role in MLC. These findings include “oedematous bulky white matter” and widespread symmetrical white matter changes in bilateral distribution, with a comparative preservation of central white matter structures. Subcortical cysts are generally seen in almost all the cases with mostly distribution in the bilateral temporal lobes anteriorly. There is generally no involvement of the grey matter. In the long term, cases may have cerebral atrophy with increased number of cysts and increase in size.

Differential Diagnosis List
Megalencephalic leukoencephalopathy (Van der Knaap disease)
Canavan disease
Alexander disease
Metachromatic leukodystrophy
Final Diagnosis
Megalencephalic leukoencephalopathy (Van der Knaap disease)
Case information
DOI: 10.35100/eurorad/case.18572
ISSN: 1563-4086