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
Treatment and prognosis
The disease is managed by treating the manifestations with antiepileptic drugs to control epileptic seizures and physical therapy to improve motor function.
History and etymology
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.
- 1. Sener RN. Demonstration of glycine peaks at 3.50 ppm in a patient with van der Knaap syndrome. AJNR Am J Neuroradiol. 2001;22 (8): 1587-9. AJNR Am J Neuroradiol (citation) - Pubmed citation
- 2. Morita H, Imamura A, Matsuo N et-al. MR imaging and 1H-MR spectroscopy of a case of van der Knaap disease. Brain Dev. 2006;28 (7): 466-9. doi:10.1016/j.braindev.2005.12.006 - Pubmed citation
- 3. Sener RN. van der Knaap syndrome: MR imaging findings including FLAIR, diffusion imaging, and proton MR spectroscopy. Eur Radiol. 2000;10 (9): 1452-5. Eur Radiol (link) - Pubmed citation
- 4. Van der knaap MS, Wevers RA, Kure S et-al. Increased cerebrospinal fluid glycine: a biochemical marker for a leukoencephalopathy with vanishing white matter. J. Child Neurol. 1999;14 (11): 728-31. J. Child Neurol. (citation) - Pubmed citation
- 5. Batla A, Pandey S, Nehru R. Megalencephalic leukoencephalopathy with subcortical cysts: A report of four cases. J Pediatr Neurosci. 2011;6 (1): 74-7. Free text at pubmed - Pubmed citation