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Table of Contents    
Year : 2019  |  Volume : 67  |  Issue : 3  |  Page : 890-892

Tumoural transformation in Van der Knaap syndrome

1 Department of Neurosurgery, Kamla Nehru Memorial Hospital, Allahabad, Uttar Pradesh, India
2 Department of Pathology, M.L.N. Medical College, Allahabad, Uttar Pradesh, India
3 Department of Neurosurgery, S.M.S. Medical College, Jaipur, Rajasthan, India
4 Department of Neurology, S.M.S. Medical College, Jaipur, Rajasthan, India

Date of Web Publication23-Jul-2019

Correspondence Address:
Dr. Pankaj Gupta
Department of Neurosurgery, Kamla Nehru Memorial Hospital, Allahabad - 211 001, Uttar Pradesh
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.263185

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How to cite this article:
Gupta P, Kumar V, Kataria R, Srivastava T, Sardana V R. Tumoural transformation in Van der Knaap syndrome. Neurol India 2019;67:890-2

How to cite this URL:
Gupta P, Kumar V, Kataria R, Srivastava T, Sardana V R. Tumoural transformation in Van der Knaap syndrome. Neurol India [serial online] 2019 [cited 2020 Jul 11];67:890-2. Available from:


Van der Knaap syndrome is a new and rare entity associated with diffuse leukoencephalopathy and cystic degeneration of white matter of the brain.[1],[2] The clinical course is usually mild and slowly progressive; however, due to lack of definite treatment, it may prove fatal. It is also known as megaloencephalic leukoencephalopathy with subcortical cyst, and has been found predominantly in the Agrawal community in India, although it has been reported sporadically from other subcontinents of world.[3] We are presenting a case of Van der Knaap syndrome in a female patient from a non-Agrawal family from Haryana, who developed tumoural transformation in the subcortical cyst. Leukodystrophies are rare, slowly progressive, chronic disorders, which mostly affect children in the first decade of life. They present with enlarged head, motor abnormalities, seizures, learning difficulties and a poor intellect. We are reporting a patient of this syndrome, who presented at the age of 52 years with tumoural transformation in the subcortical cyst. To the best of our knowledge based on PubMed and Google database review, we are reporting the first case of tumoural transformation in Van der Knaap syndrome.

A 52-year old female patient who had difficulty in walking and seizure episodes for the last 5 years and had been investigated for and diagnosed as a case of Van der Knaap syndrome, now presented with sudden onset, rapidly progressive headache and altered sensorium for the last 5 days. On examination, the patient was drowsy but arousable (E3V3M5) with impairment of comprehension. Previous MRI was suggestive of cystic areas in bilateral anterior frontal and temporal regions with hypointensity in bilateral periventricular and subcortical white matter areas, representative of leukoencephalopathy or demyelination, suggesting the diagnosis of Van der Knaap syndrome [Figure 1]. The recent contrast CT scan showed a 55 X 30 X 50 mm solid-cystic left temporal mass with heterogenous enhancement in the medial part of the lesion with subfalcine herniation and midline shift of 7 mm to the right side [Figure 2]. On comparison to the previous MRI done 5 years ago, there was an increase in the size of the lesion in the left temporal region with development of pressure effect. Gross total removal of the tumour and augmented duraplasty using pericranial patch was done. The mass was solid-cystic, soft-to-firm, pinkish-grey in colour with moderate vascularity. Histopathological examination was suggestive of World Health Organisation grade II astrocytoma, based on hypervascularity, pleomorphism and hypercellularity [Figure 3]. The postoperative period was uneventful and the patient did well. There was found no evidence of recurrence at a 3-year follow-up period.
Figure 1: MRI showing diffuse altered signal intensity in bilateral centrum semiovale and corona radiata region, suggestive of demyelination (asterisk) with a large cystic lesion in bilateral temporal polar region (arrow) with diffuse cerebral atrophy

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Figure 2: Contrast CT scan showing the solid-cystic lesion in the left temporal region with enhancement of medial solid portion of the mass with pressure effect and midline shift to the right side (arrow)

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Figure 3: Photomicrograph (40X) showing a moderately cellular tumour with proliferation of astrocytes, displaying moderate nuclear atypia in a fibrillary background, suggestive of WHO grade II diffuse fibrillary astrocytoma

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Van der Knaap syndrome is an autosomal recessive disorder with mutation in the megalencephalic leukoencephalopathy (MLC1) gene, producing a defect in myelin. This was first described by Vander Knaap in 1925.[1],[2],[3] Classically, it appears between birth and the first decade of life in the form of macrocrania, learning difficulties, spasticity, ataxia and seizure disorder. The first case in India was reported by Singhal et al., in 1996 and the authors found that 26 out of their 30 cases belonged to the Agrawal community of northern India.[4],[5] The age of presentation varied from birth to 27 years. In 2003, Singhal et al., reported a case series of Vander Knaap syndrome found in 63 Agrawal families out of 70.[4],[5] On MR spectroscopy, the lesions show a moderate decrease in N-acetyl aspartate/creatine (NAA/Cr) and choline/Cr peak.[6]

Our case is unique in many perspectives. The patient was a 52-year old female patient from Haryana [northern India] in whom the diagnosis was first established at the age of 47 years. Later, in the due course of 5 years of the disease onset, the subcortical cyst underwent tumoural transformation. Usually, patients are diagnosed in the first decade of life and the maximum survival is upto the third decade without any tumoural transformation.

MRI is diagnostic and shows the diffuse degeneration of white matter of the brain with subcortical cysts, especially in the anterior temporal and fronto-parietal regions with cerebral atrophy. Prenatal diagnosis is possible with DNA analysis by amniocentasis at 16-18 weeks of gestation.[1],[4] Differential diagnosis includes Canavas disease, Alexander disease, and infantile onset GM1 and GM2 gangliosidosis. So far, all attempts to treat Van der Knaap syndrome have failed. The mainstay of treatment is supportive in the form of acetazolamide, anticonvulsants and physical therapy.[2],[5]

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There are no conflicts of interest.

  References Top

van der Knaap MS, Barth PG, Gabreals FJ, Franzoni E, Begeer JH, Stroink H, et al. A new leukoencephalopathy with vanishing white matter. Neurology 1997;48:845.  Back to cited text no. 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;37:324-34.  Back to cited text no. 2
Gorospe JR, Singhal BS, Kainu T, Wu F, Stephan D, Trent J, et al. Indian Agarwal megalencephalic leukodystrophy with cysts is caused by a common MLC1 mutation. Neurology 2004;62:878-82.  Back to cited text no. 3
Singhal BS, Gurshahani RD, Udant VP, Binivale AA. Megaloencephalic leukodystrophy in an Asian Indian ethnic group. Pediatr Neurol 1996;14:241-96.  Back to cited text no. 4
Singhal BS, Gorospe GR, Natdu S. Megaloencephalopathy with subcortical cyst. J Child Neurol 2003;18:646-53.  Back to cited text no. 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. Neuroradiol 2003;45:137-42.  Back to cited text no. 6


  [Figure 1], [Figure 2], [Figure 3]


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