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NEURORADIOLOGY Table of Contents   
Year : 2006  |  Volume : 16  |  Issue : 4  |  Page : 733-734
Van der knaap disease, a megalencephalic leukoencephalopathy

Department of Radiodiagnosis and Imaging, Kasturba Medical College, Manipal, India

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Keywords: Van der Knaap Disease, Megalencephalic Leukoencephalopathy

How to cite this article:
Rajagopal K V, Ramakrishnaiah R H, Avinash K R, Lakhkar B N. Van der knaap disease, a megalencephalic leukoencephalopathy. Indian J Radiol Imaging 2006;16:733-4

How to cite this URL:
Rajagopal K V, Ramakrishnaiah R H, Avinash K R, Lakhkar B N. Van der knaap disease, a megalencephalic leukoencephalopathy. Indian J Radiol Imaging [serial online] 2006 [cited 2021 Mar 2];16:733-4. Available from:

   Introduction Top

Megalencephalic leukoencephalopathy (MLC) with subcortical cysts is a rare disease first described by van der Knaap et al, in 1995 [1]. Megalencephalic leukoencephalopathy with subcortical cysts is a relatively new entity of neurodegenerative disorder characterized by infantile onset macrocephaly, cerebral leucoencephalopathy and mild neurological symptoms and an extremely slow course of functional deterioration [1]. Megalencephalic leukoencephalopathy with subcortical cysts is a rare disease with autosomal recessive inheritance [2]. The degree of macrocephaly is variable and can be as much as 4-6 SD above the mean. Almost all patients have epilepsy from an early age. Some patients have died in their 2nd and 3rd decades but few may live till fourth decade. We report a 2-year-old boy diagnosed to have this disease.

   Case report Top

A 2 year-old boy, born of non-consanguineous marriage in a muslim community from Kerala, with uneventful birth history, presented with progressively increasing head size noticed from 1 year of age. He attained social smile by 3 months and head control by 7 months of age. He was not able to sit or walk himself.

On examination, there was macrocephaly with head circumference of 61 cm. He was not able to comprehend or speak. Sensory system was normal and there were no cerebellar signs. Eye examination and abdominal examination were unremarkable.

MR brain revealed extensive bilaterally symmetrical white matter changes, which are hypointense on T1 weighted [Figure - 1]A and hyperintense on T2 weighted [Figure - 1]B and FLAIR images suggestive of extensive demyelination. Additionally, large well defined symmetrical subcortical cysts were noted in anterior temporal lobe and which are hypointense on T1 [Figure - 2]A, hyperintense on T2 and suppressed on FLAIR images [Figure - 2]B consistent with a diagnosis of Megalencephalic leukoencephalopathy.

His brother died at the age of 2 years, the cause of which is not known. He was treated symptomatically with use of physiotherapy.

   Discussion Top

The diagnosis of MLC can be made with confidence in patients with typical clinical findings and characteristic abnormalities on cranial MR. MLC is known for its mild neurological signs and symtoms in the setting of a very abnormal MR findings. Macrocephaly is present at birth or, more commonly, develops within the first year of life in all patients. Early development is normal or mildly delayed. Slow deterioration of motor functions with cerebellar ataxia and mild spasticity usually starts in early childhood. Some patients have extrapyramidal movement abnormalities with dystonia and athetosis, usually as a late finding. Mental decline occurs later and is much milder than motor decline. Most patients have epileptic seizures.

In typical cases, the MR findings are often diagnostic of MLC. MR shows 'swollen white matter' and diffuse supratentorial symmetrical white matter changes in the cerebral hemispheres with relative sparing of central white matter structures like the corpus callosum, internal capsule, and brain stem. Subcortical cysts are almost always present in the anterior temporal region and are also frequently noted in frontoparietal region. Grey matter is usually spared. Gradually the white matter swelling decreases and cerebral atrophy may ensue. The subcortical cysts may increase in size and number.

In India, majority of the patients belong to the Agarwal community [3]. Our patient did not belong to this community. Indian patients with megalencephaly and MR changes that show extensive white matter changes with temporal cysts should raise suspicion for MLC [3]. This disease has been assigned to the gene, MLC1, and is localized on chromosome 22qtel [4]. Moderate decrease in NAA/ Cr and Choline/Cr ratios have been reported in patients with MLC on MR spectroscopy [5].

The differential diagnosis of MLC includes Canavan's disease, Alexander disease, infantile-onset GM2 and GM1 gangliosidosis. These conditions have relentlessly progressive infantile onset leukoencephalopathy that is freequently fatal within first decade of life, however MLC has remarkably slow course of deterioration in neurologic function. MLC must be included in differential diagnosis of macrocephaly with early onset leukoencephalopathy [6].

   References Top

1.Van Der Knaap MS, Barth PG, Stroink H, van Nieuwenhuizen O, Arts WF, Hoogenraad F, et al. Leukoencephalopathy with swelling and a discrepantly mild clinical course in eight children. Ann Neurol, 1995; 37: 324-334.  Back to cited text no. 1    
2.Koussa S, Roukoz H, Rizk T, Megarbane A. Megalencephalic leucoencephalopathy with subcortical cysts: a study of a Lebanese family and a review of the literature. Rev Neurol (Paris). 2005 Feb;161(2):183-91  Back to cited text no. 2    
3.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.  Back to cited text no. 3    
4.Pascual-Castroviejo I, van der Knaap MS, Pronk JC, Garcia-Segura JM, Gutierrez-Molina M, Pascual-Pascual SI. Vacuolating megalencephalic leukoencephalopathy: 24 year follow-up of two siblings.Neurologia. 2005 Jan-Feb;20(1):33-40.  Back to cited text no. 4    
5.Brockmann K, Finsterbusch J, Terwey B, Frahm J, Hanefeld F. Megalencephalic leucoencephalopathy with subcortical cysts in an adult: quantitative proton MR spectroscopy and diffusion tensor MRI. Neuroradiology 2003;45:137-42.  Back to cited text no. 5  [PUBMED]  [FULLTEXT]
6.Krishnan KH, Pauline CL, Kumaresan G, Mallika TK. Megalencephalic leukoencephalopathy with subcortical cysts. Indian Pediatr. 2005 Jan;42(1):60-3.  Back to cited text no. 6    

Correspondence Address:
K V Rajagopal
Department of Radiodiagnosis and Imaging, Kasturba Medical College. Manipal. Pin:576104 Karnataka State
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0971-3026.32334

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