What Is Megalencephalic Leukoencephalopathy with Subcortical Cysts?

Megalencephalic Leukoencephalopathy with Subcortical Cysts (MLC) is an inherited disease that causes seizures and developmental delay in affected infants and children, followed by a deterioration of motor skills and intellectual abilities later in life. Additionally, individuals with MLC demonstrate changes in brain structure, including the development of cysts that are visible on brain scans. The condition is most often caused by mutations in the MLC1 gene.

Many infants with MLC are born with disproportionately large heads, while others develop this symptom in the first year of life. After the first year, the growth of the head usually normalizes and becomes proportionate to the body. This is often accompanied by a mild delay in motor skills and the development of epileptic seizures. Most children with MLC learn to walk independently for at least several years. While some retain the ability to walk for decades, many will experience deteriorating motor skills beginning in childhood. With time, individuals with MLC may demonstrate an inability to coordinate muscle movement (ataxia) and may exhibit significant muscle stiffness (spasticity). Many will require wheelchairs or other assistive devices by their early teens or twenties. Some individuals may also experience difficulties with swallowing and speech. Decline in intellectual abilities is slower in progression and generally begins after the decline in motor skills.

How Common Is Megalencephalic Leukoencephalopathy with Subcortical Cysts?

MLC is extremely rare, although the precise prevalence of the condition in the general population is unknown. Mutations in the MLC1 gene are estimated to account for approximately 75% of MLC cases and have been found in individuals of Middle Eastern, Turkish, Japanese, and Libyan Jewish descent, among others. In addition, it has been suggested that the condition may be more common in the Agarwali Indian and Turkish populations.

How Is Megalencephalic Leukoencephalopathy with Subcortical Cysts Treated?

There is no treatment or cure for the underlying cause of MLC. Treatments address the symptoms of the disease, such as medications to control seizures and physical therapy to improve motor skills.

What Is the Prognosis for an Individual with Megalencephalic Leukoencephalopathy with Subcortical Cysts?

MLC is slowly progressive. The majority of individuals with the condition are confined to a wheelchair in adolescence or early adulthood, although those with more severe disease may lose the ability to walk much earlier. Lifespan may be also be shortened in individuals with MLC, with death occurring as early as the late teens in some cases and as late as the forties or fifties in others.

Other names for
megalencephalic leukoencephalopathy with subcortical cysts

  • Leukoencephalopathy with swelling and cysts
  • MLC
  • Megalencephalic leukoencephalopathy with subcortical cysts
  • Vacuolating megalencephalic leukoencephalopathy with subcortical cysts
  • Van der Knaap disease


  • Ilja et al., 2006, Hum Mutat, 27(6):505-12, PMID: 16652334
  • Leegwater et al., 2002, Hum Genet, 110(3):279-83, PMID: 11935341
  • Online Inheritance in Man, OMIM [#604004], 2016, https://www.omim.org/entry/604004
  • Van der Knaap et al., 2011, https://www.ncbi.nlm.nih.gov/books/NBK1535/
  • Van der Knaap et al., 2012, Lancet Neurol, 11(11):973-85, PMID: 23079554