Megalencephalic leukoencephalopathy with subcortical cysts (MLC1)

Megalencephalic leukoencephalopathy with subcortical cysts (MLC1) is a very rare disorder affecting the ‘white matter’ of the brain, often leading to progressive loss of physical, and sometimes mental, skills over very many years. 

The name comes from the Greek and describes the features of the condition.

What causes MLC1?

MLC1 is a disorder mainly affecting the white matter (nerve fibres) of the brain. The white matter principally controls motor, rather than intellectual, function. The cause is a genetic mutation – the identified genes being MLC1 and MLC2A.

How is MLC1 diagnosed?

The diagnosis is made, initially, on the history of the child’s symptoms. Eventually, an MRI brain scan shows abnormal swelling of the white matter (leukoencephalopathy) and cysts in the temporal or parietal areas of the brain which are characteristic of MCL1. These scan features, however, may not be apparent until several years have elapsed.

The diagnosis can often be confirmed by genetic testing on a blood sample, although this may not be conclusive as there are likely to be other, as yet unidentified, causative genes.

Does MLC1 have an alternative name?

In the late 1990s, Dr Van der Knaap described the condition, based on its features and the specific appearances of the brain scan. It was sometimes known as Van der Knapp disease and megalencephalic leukoencephalopathy.

Is MLC1 inherited?

MLC1 is an autosomal recessive disorder. This means that both parents are carriers of the condition. 

Human beings have about 30,000 to 40,000 different genes, each of which has a function in making an individual person. The genes are arranged in pairs (one of the pair from each parent) on 23 chromosomes. 

Inevitably, some of these genes are faulty. A normal gene can overcome a faulty one, but if both genes in the pair are faulty, the genetic instructions cannot work. 

Most people carry different faulty genes but in MLC1 (and other recessive conditions), parents, though healthy themselves, carry the same faulty genes, and risk passing them on to their children. Each pregnancy carries:

  • a 25 per cent chance of the child being affected

  • a 75 per cent chance of the child not being affected

Is prenatal testing available?

If the genetic mutation has been identified in the affected child and parental DNA has been tested, pre-natal diagnosis is possible.

How common is MLC1?

It is estimated that the incidence in the UK is approximately one in 500,000.

How does the disease progress?

The infant will have few or no apparent problems in the first year but, if measured, the head size may be noted to be larger than expected (megalencephaly). 

Between the ages of two and ten years, the child shows signs of increasing unsteadiness (ataxia) usually followed by stiffness of muscle tone (dystonia) and involuntary writhing movements (athetosis) and, after very many years, progressive loss of mental skills.

As MLC1 is a relatively newly described condition, there is a lot still to learn about it but it is already clear that the features and prognosis are extremely variable.

Some children are wheelchair users in childhood or their teenage years, others not until mid-adulthood. Many children will be prone to epileptic seizures and, as learning difficulties become more obvious, behaviour problems may also develop.

Children whose motor skills and balance are more severely affected are likely to have some slurring of speech (dysarthria) and incoordination of swallowing (dysphagia). In some children, mild head trauma may induce a sudden deterioration, often quite severe, usually followed by a slow improvement.

In the most severe forms of MLC1, where symptoms are worsening rapidly or repeated setbacks are occurring, life expectancy can be significantly reduced. In these situations, the child or young adult is unlikely to be conscious of what is happening but family and carers will be aware of their increasing frailty. Therefore death would probably be anticipated and relatively peaceful when the time comes.

There is a recognised group of children who, despite initial gross-motor delay and increased head size, improve and stabilise (with or without a degree of disability) and the MRI features may also improve. These children have a different gene mutation: MLC2B.

Is there any treatment for MLC1?

Although there is no treatment yet available that can stop the condition, every effort is made to ensure that the child and young adult enjoy as much independence and life experiences as their friends. 

Help will be provided with mobility aids when necessary and any symptoms, including seizures, will be treated if and when they occur. In view of the risks associated with head injuries, it is prudent to take extra reasonable precautions to try to avoid these.

Is any research being done?

Research is progressing, particularly in the field of genetics. With the identification of the MLC1, MLC2A and also MLC2B gene mutations, it is hoped that, in time, understanding of what the gene does will advance with the eventual hope of gene therapy. 

Unfortunately this research is extremely complex and may seem very slow to the sufferer and their family. 

A neurologist and the support group mentioned below can keep you informed of research progress.

Compiled by: 
The Neurology Liaison Nurse Specialist in collaboration with the Child and Family Information Group.
Last review date: 
July 2016
Ref: 
2016F0705

Disclaimer

Please note this is a generic GOSH information sheet so should not be used for the diagnosis or treatment of any medical condition. If you have specific questions about how this relates to your child, please ask your doctor.