Which are the causes of Megalencephalic Leukoencephalopathy With Subcortical Cysts?

Megalencephalic Leukoencephalopathy With Subcortical Cysts (MLC) is a rare genetic disorder that affects the brain and nervous system. It is characterized by the presence of fluid-filled cysts in the subcortical white matter of the brain, as well as abnormal enlargement of the brain (megalencephaly) and white matter abnormalities (leukoencephalopathy).

The exact cause of MLC is still not fully understood, but it is known to be caused by mutations in two specific genes: MLC1 and MLC2A. These genes provide instructions for producing proteins that are involved in the maintenance and function of brain cells, particularly the cells that make up the white matter of the brain.

MLC1 gene mutations: Mutations in the MLC1 gene are responsible for the majority of cases of MLC. The MLC1 protein is thought to play a role in regulating the movement of water and ions in and out of brain cells. Mutations in this gene disrupt the normal function of the protein, leading to the formation of cysts and the degeneration of white matter in the brain.

MLC2A gene mutations: Mutations in the MLC2A gene are less common and account for a smaller percentage of MLC cases. The MLC2A protein is believed to work together with the MLC1 protein to maintain the integrity of brain cells and regulate their water and ion balance. Mutations in this gene also disrupt the normal function of the protein, resulting in the characteristic features of MLC.

MLC is inherited in an autosomal recessive manner, which means that an affected individual must inherit two copies of the mutated gene (one from each parent) in order to develop the disorder. If both parents are carriers of a single mutated gene, they have a 25% chance of having an affected child with each pregnancy.

While the specific mechanisms by which MLC gene mutations lead to the development of the disorder are not fully understood, it is believed that the disruption of water and ion balance in brain cells plays a crucial role. This imbalance can lead to the formation of cysts and the degeneration of white matter, ultimately resulting in the symptoms and characteristics of MLC.