More symptom information
Learn more about specific symptoms of this leukodystrophy in these pages.
Also known as: MLC; Van der Knapp syndrome; vacuolating leukodystrophy with subcortical cysts; megalencephaly-cystic leukodystrophy syndrome
Megalencephalic Leukodystrophy with subcortical cysts (MLC) is a rare genetic disorder affecting the brain’s white matter caused by mutations in the MLC1 or the HEPACAM gene. It is characterized by the abnormal enlargement of the brain (megalencephaly) and the presence of fluid-filled cysts within the subcortical regions. MLC typically presents in early childhood with neurological symptoms, such as developmental delay, movement and coordination difficulties and seizures. Treatment mainly focuses on managing symptoms and providing supportive care to improve the affected individual’s quality of life.
A new diagnosis can be overwhelming as it brings unique challenges and adjustments, but it is important to remember that you are not alone.
In around 75% of cases (type 1), MLC is caused by mutations in the MLC1 gene. This gene creates a protein found primarily in the brain, at the junctions between some types of cell. It is unknown how this leads to impairment of brain function.
MLC can also be caused by mutations of the HEPACAM gene; this results in MLC type 2A or 2B. The HEPACAM gene creates a different protein which is important to cell junctions in the brain.
Around 5% of those with this condition do not have mutations in the MLC1 gene or the HEPACAM gene. The cause of MLC in these people is unclear.
Autosomal recessive – Type 1 and 2A: In autosomal recessive conditions, two copies of the genetic mutation are needed to cause the condition. We all have two copies of every gene, one from our mother and one from our father. The parents of someone with an autosomal recessive condition both carry one copy of the gene with a genetic mutation. Therefore, someone with an autosomal recessive condition has two copies of the genetic mutation, one copy from each parent. Each child of parents that both carry the genetic mutation will have a 25% chance of having the condition, a 50% chance of carrying the genetic mutation (like the parent), and a 25% chance of not having the condition.
Autosomal dominant – Type 2B: In autosomal dominant conditions, only one copy of the genetic mutation is needed to cause the condition. We all have two copies of every gene, one from our mother and one from our father. Someone with an autosomal dominant condition has one parent with a copy of the genetic mutation and the condition themselves. Therefore, someone with an autosomal dominant condition has a genetic mutation on one copy of the gene from their parent with the condition. Each child of a parent with the genetic mutation will have a 50% chance of having the condition and a 50% chance of not having the condition.
Genetic counselling is essential for affected families due to the inheritance pattern of the condition. This is available at hospitals and Regional Genetic Centres. Please contact your doctor if you have any questions.
Learn more about genetic testing and counselling here.
MLC Type 1 and Type 2A have almost identical symptoms (with different causes). MLC Type 2B has similar symptoms but these often begin to improve after one year.
Megalencephaly is typically evident at birth or within the first year, and individuals may develop cysts in the brain. Spasticity and ataxia are common, affecting walking abilities in some but not all those affected. Minor head trauma may worsen movement difficulties and can lead to coma. Dystonia, swallowing difficulties, dysarthria, and athetosis are common. Most will suffer from seizures, but will not experience severe intellectual disability.
Learn more about specific symptoms of this leukodystrophy in these pages.
Although there is currently no specific treatment for this leukodystrophy, there is condition management information that may be useful for you in managing your or your loved one’s leukodystrophy.
There may be a current clinical trial, natural history study or patient registry for your condition. Check our current research page and ask your specialist doctor for more information.
We understand that research is a significant priority and source of hope for the leukodystrophy community. There is more research in leukodystrophy now than ever before. Alex TLC actively promotes and supports research in a number of ways.
Every month we update our database of research summaries with the most recent research. This includes summaries of leukodystrophy articles, clinical trials and pharmaceutical press releases. Our summaries allow our community to read about relevant recent research developments in a format that is easily understood.
Learn about the ways in which we can help in the how we support you section. When you or a family member been diagnosed with a leukodystrophy it may be difficult to know where to go for more advice – this information could help.
Our services and equipment section is here to help leukodystrophy patients and their families manage their condition. All information is based on our knowledge of UK services, however, our team are happy to receive support requests from other countries – email us.
You may be introduced to many different medical professionals which you may find confusing. View our guide to the health and care professionals you may encounter, with short descriptions about what they do.
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