Megalencephalic leukoencephalopathy with subcortical cysts

Megalencephalic leukoencephalopathy with subcortical cysts, also known as Van der Knaap disease, refers to a rare inherited autosomal recessive disease characterised by diffuse subcortical leukoencephalopathy associated with white matter cystic degeneration. 

The age at symptoms manifestations ranges from birth to 25 years, with a median age of 6 months 5.

Patients typically present with megalencephaly during the 1st year of life associated with mild motor developmental delay and seizures 5. There is also a gradual onset of ataxia, spasticity, and sometimes extrapyramidal findings. Mild mental deterioration can be observed late in life. 

It is sometimes classified as a megalencephalic leukoencephalopathy.

It is thought to carry an autosomal recessive inheritance, and the gene locus has been mapped as MLC 1 gene at chromosome 22q 4,5.

Elevated levels of glycine have been reported in CSF 1.

Shows a megalencephalic brain with bilateral cystic lesions of CSF intensity mainly affecting the anterior temporal lobes. There can also be a wide diffuse signal abnormality and features of swelling affecting white matter. 

The hallmarks of radiological diagnosis are the following features: 

  • subcortical white matter involved early in course of disease with involvement of the subcortical U-fibers
  • subcortical cysts especially temporal poles and frontoparietal lobes

The disease is managed by treating the manifestations with antiepileptic drugs to control epileptic seizures and physical therapy to improve motor function.

Bhim Sen Singhal described a megalencephalic leukodystrophy series of cases in 1991 5. It is named after Marjo van der Knaap, a Dutch physician 4

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Article information

rID: 20282
Section: Pathology
Tag: cases
Synonyms or Alternate Spellings:
  • Vacuolating megalencephalic leukoencephalopathy
  • van der Knapp syndrome
  • Megalencephalic leukoencephalopathy with subcortical cysts (MLC)
  • Megalencephalic leukoencephalopathy with subcortical cysts
  • van der Knaap syndrome
  • Van der Knaap disease

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