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NEURORADIOLOGY Table of Contents   
Year : 2004  |  Volume : 14  |  Issue : 2  |  Page : 125-127
Infantile-onset leukoencephalopathy with swelling and a discrepantly mild clinical course (Vander knaap disease) - a case report

Department of Radiodiagnosis, NSCB Medical College, Jabalpur (M.P), India

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Keywords: Leukodystrophy, Vander Knaap disease, MRI

How to cite this article:
Pande S, Agarwal R, Nagpal T, Kaur A. Infantile-onset leukoencephalopathy with swelling and a discrepantly mild clinical course (Vander knaap disease) - a case report. Indian J Radiol Imaging 2004;14:125-7

How to cite this URL:
Pande S, Agarwal R, Nagpal T, Kaur A. Infantile-onset leukoencephalopathy with swelling and a discrepantly mild clinical course (Vander knaap disease) - a case report. Indian J Radiol Imaging [serial online] 2004 [cited 2021 Mar 1];14:125-7. Available from:

   Introduction Top

A case of Vander Knaap disease defined on the basis of clinical and Neuro-imaging finding on MRI is reported. We are reporting this case because despite the relative rarity a diagnosis of the disease can be made in the presence of characteristic MR features of diffuse supratentorial white matter abnormality with subcortical cysts despite discrepantly mild clinical abnormality.

   Case report Top

A nine months old male baby presented with increasing head size since birth. On examination the patients head circumference was seen to be well above + 2 SD for the age of the patient. There was no evidence to support sign and symptoms of raised intracranial tension, such as vomiting, papilloedema etc. No neurological deficit was present. Routine laboratory tests including CSF studies were done and were found to be normal. He is the first child of his parents and is born of non consanguinous relationship.

MR Imaging was done on a 0.3T permanent magnet MRP. 7000 Hitachi Tokyo Japan. Imaging was done in the three orthogonal planes using T1WSE, T1IR, T2W FSE and FLAIR sequences.

The MR study revealed diffusely abnormal and swollen white matter with obliteration of the peripheral sulcal spaces and thinning of the overlying cortex. [Figure - 1] The white matter showed diffuse hypointensity on T1WIR imaging [Figure - 2] and hyperintensity on T2 WI [Figure - 3] sequence. Well defined cysts on FLAIR images [Figure - 4],[Figure - 5] were noted in the subcortical white matter of temporal tips, frontal and parietal lobes. There was sparing of the central gray matter and the deep periventricular white matter structures [Figure - 6]. The brainstem was uninvolved and mild hyper intensity on T2W & FLAIR sequences in the bilateral cerebellar hemispheres were noted [Figure - 7].

Based on the MR features and clinical findings a diagnosis of Vander Knaap's disease was given.

   Discussion Top

Vander Knaap disease is a recently identified syndrome [1] which can present at birth and more frequently during the first year of life. It is characterised by macrocephaly which is variable and impressive in some of the patients. Initially normal or nearly normal mental and motor development is seen in most cases and is mildly delayed in some.

In most cases these early manifestations are followed by evolution of pyramidal signs and symptoms, cerebellar ataxia, epilepsy and in older patients dystonia and athetosis [2]. Etiology of the disease is unknown. However, the disease gene has recently been mapped to a 3 cM interval between D2251161 and the telomere of chromosome 22q [3].

The disease process is relatively mild as compared to the neuroradiological findings [4],[5]. As the disease has been known since relatively short time little information is available about the average life span. Some patients have died in their teens or twenties, but others are alive in their forties.

MR imaging features of the disease is diffusely abnormal and mildly swollen cerebral hemispheric white matter. Central white matter structures including corpus callosum, internal capsule & brainstem are well preserved, although they are not usually entirely normal. The cerebellar white matter usually has a mildly abnormal signal and is not swollen. Subcortical cyst are invariably present in the anterotemporal region and often in the frontoparietal region [2],[6]. Overtime the white matter swelling decreases and cerebral atrophy ensues, the cysts become huge, occupying a large part of the frontoparietal white matter. Pathologically splitting of myelin sheath between the lamellae is seen consistent with an oedematosus process with sparing of axons [7]. Despite all these changes no abnormalities are found in laboratory investigations for metabolic derangement. There is no evidence of lysosomal dysfunction, in particular no evidence of sphingolipidoses, peroxisomal dysfunction or mitochondrial disorder. No abnormalities of amino acid and organic acid metabolism are found. CSF, GABA, amino acid and amines are normal. [1]

It is essential to distinguish it from other diseases of white matter eg, Canavan's disease, Alexander and 1-2 hydroxyglutaric aciduria and merosin deficient congenital muscular dystrophy. In Canavan's disease there is involvement of the thalamus and global pallidus not found in our patient. Alexander disease shows typical contrast enhancement in periventricular region, caudate nuclei and thalami on MR imaging and the frequent presence of hydrocephalus and the often prominent cavitation starting in the frontal periventricular white matter. None of these is seen in our case. In L-2- hydroxyglutaric aciduria additional involvement of caudate nuclei, putamen, dentate nuclei and severe atrophy of the cerebellar vermis is seen on MR imaging which is not observed in this case. The MRI abnormalities observed in merosin deficient congenital muscular dystrophy are very similar to those observed in the disease described here but typical subcortical cysts are lacking and no evidence of muscular dystrophy was observed in our case. Hence MRI features are highly accurate in diagnosing the disease and there are no specific laboratory tests to diagnose the disorders. MRI also allows the differentiation of Vander Knaap's disease from other leukodystrophies simulating it.

   References Top

1.MS vander Knaap, J. Valk. Magnetic resonance of myelination and myelin disorders : Infantile-Onset Leukoencephalopathy with Swelling and a Discrepantly Mild Clinical Course. 2nd ed. Springer, 1995: 277-281.  Back to cited text no. 1    
2.Vander Knaap MS, Barth PG, Stroink H, Van Nieuwenhuizen O, Arts WFM, Hoogenraad F, Valk J. Leukoencephalopathy with swelling and discrepanthy mild clinical course in eight children. Ann Neurol 1995; 37: 324-34.  Back to cited text no. 2    
3.Topcu M, Gartioux, Ribierra F, Yalcinkaya C, Tokus E, Oztekin N, Beckmann JS, Ozguc M, Seboun E: Vacuolating megaleucephalic leukoencephalopathy with subcortical cysts, mapped to chromosome 229tel, Am J Hum Genet 2000; 60: 733-9.  Back to cited text no. 3    
4.Goutieres F, Boulloche J, Bourgeois M, Aicardi J: Leukoencephalopathy, megalencephaly and mild clinical course: a recently individualized familial leukodystrophy: a report on five new cases. J Child Neurol 1996; 11: 439-44.  Back to cited text no. 4    
5.Topcu M, Saatci J, Topcuoglu MA, Kose G, Kaunak B: Megalencephaly and leukodystrophy with mild clinical course: A report on 12 new cases. Brain Dev 1998; 20: 142-53.  Back to cited text no. 5    
6.Mejaski-Bosnjak V, Besenki N, Brockmann K, Pouwels PJ, Frahm J, Hanefield FA. Cystic leukoencephalopathy in a megalencephalic child: Clinical and magnetic resonance imaging/ magnetic resonance spectroscopy findings. Pediatr Neurol 1997; 16: 347-50.  Back to cited text no. 6    
7.Vander Knaap MS, Barth PG, Vrensen GF, Valk J. Histopathology of an infantile onset spongiform leukoencephalopathy with a discrepantly mild clinical course. Acta Neuropathol 1996: 92: 206-12.  Back to cited text no. 7    

Correspondence Address:
S Pande
Department of Radiodiagnosis, NSCB Medical College, Jabalpur (M.P)
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Source of Support: None, Conflict of Interest: None

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[Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6], [Figure - 7]

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