May 2026

CASE HISTORY

A 5-year-old male child presented with complaints of recurrent generalized tonic–clonic seizures and right-sided weakness ,predominantly involving the lower limb along with anger outbursts and abnormal behaviour.

No history of fever, head trauma, vision loss, sensory loss, or headache.

No family history of seizure disorder or chronic neurological illness.

Birth history: Full-term normal vaginal delivery, birth weight 2.8 kg, no NICU stay

CASE CONTRIBUTED BY-

Dr Somya Gupta – 3rd year Resident , Department of Radiodiagnosis, Kalinga Institute of Medical Sciences , Bhubaneswar , Odisa

Dr. Tapas kumar sahu , Assistant Professor ,Department of Radiodiagnosis, Kalinga Institute of Medical Sciences , Bhubaneswar , Odisa

Dr. Basanta Manjari Swain (HOD and Professor),Department of Radiodiagnosis, Kalinga Institute of Medical Sciences , Bhubaneswar , Odisa

DESCRIPTION

A and B  :Axial section of T2 sequence and axial section of FLAIR sequence shows a diffuse, symmetrical  hyperintensity in  bilateral cerebral white matter including subcortical U-fiberss. The white matter appears swollen, without significant volume loss. Relative sparing of deep white matter

C: Axial FLAIR sequence shows few well-defined subcortical cysts  in the anterior temporal lobes bilaterally

D: Axial section of Diffusion weighted sequence shows no abnormality

E: 3D Sagittal cube FLAIR FS  sequence shows relatively increased fronto-occipital dimension, consistent with macrocephaly .

Diagnosis:Megalencephalic Leukoencephalopathy with Subcortical Cysts (MLC), also known as Van der Knaap disease

Background

Megalencephalic Leukoencephalopathy with Subcortical Cysts (MLC), also known as Van der Knaap disease, is a rare inherited leukodystrophy .

It follows predominantly an autosomal recessive inheritance pattern

Pathophysiology

MLC is caused by mutations in:

MLC1 (≈75% cases)

HEPACAM (≈20% cases)

These genes encode proteins involved in astrocytic membrane function and regulation of brain water and ion homeostasis.

Defective astrocyte function leads to: Impaired ion and water regulation leading to white matter swelling

,vacuolation of myelin and Formation of subcortical cysts

The disease produces intramyelinic vacuolation rather than primary demyelination.

Classical Features

Macrocephaly (at birth or infancy; earliest and most consistent sign)

Delayed motor milestones

Early-onset seizures Mild early cognitive impairment with progressive Ataxia ,Spasticity ,Dysarthria

Key MRI Findings

Diffuse bilateral symmetric T2/FLAIR hyperintensity of subcortical and deep white matter with corresponding T1 hypointensity

“Swollen white matter” appearance in early stage

Relative sparing of deep grey nuclei and brainstem

Subcortical cysts, predominantly in: Anterior temporal lobes (classical) and Frontoparietal regions

Structures Typically Spared:

Basal ganglia

Thalami

Brainstem

Cerebellar white matter (early stage)

Diffusion Imaging: Usually no true diffusion restriction

Differential Diagnosis-

Canavan disease

Alexander disease

metachromatic leukodystrophy

others causes of megalencephaly

other leukoencephalopathies

References

1) Roy U, Joshi B, Ganguly G. Van der Knaap disease: a rare disease with atypical features. BMJ Case Rep. 2015 Jul 22;2015:bcr2015209831. doi:10.1136/bcr-2015-209831.

2) Jhancy M, Al Homsi A, Chowdhury F, Hossain S, Ahamed R. Van der Knaap Disease (Vanishing White Matter) – Unusual Presentation in a Neonate: A Case Report. Neurol India. 2020 May-Jun;68(3):669-672. doi:10.4103/0028-3886.289018.

3) Das S, Dhibar T. Van der Knaap Disease: A Case Series Highlighting Clinical and Radiological Features. Int J Anat Radiol Surg. 2025 Sep;14(5):RS01-RS03. doi:10.7860/IJARS/2025/81128.3062