Megalencephalic leukoencephalopathy with subcortical cysts (MLC, or Van der Knaap disease) is a form of hereditary CNS demyelinating disease. It belongs to a group of disorders called leukodystrophies. It is characterized by early-onset enlargement of the head (macrocephaly) as well as delayed-onset neurological deterioration to include spasticity, epilepsy, and lack of muscular coordination. MLC does not appear to be a disease that is fatal at birth or early in life despite its symptoms, although the number of patients throughout history known to have the disease is fairly limited.It belongs to a group of disorders called leukodystrophies. A series of cases with megalencephalic leukodystrophy were described by the Indian neurologist Bhim Sen Singhal (1933-) in 1991. However, it is sometimes referred to as Van der Knaap disease after the Dutch neurologist Marjo van der Knaap who described another series of cases with clinical and radiological features in 1995.There are three types of Megalencephalic leukoencephalopathy distinguished by the affected gene: Type 1 caused by autosomal recessive mutations on the MLC1 gene, Type 2A an autosomal recessive mutation on the HEPACAM gene, and Type 2B an autosomal dominant mutation on the HEPACAM gene. Signs and Symptoms
Head
Macrocephaly
The disease is characterized by megalencephaly, the enlargement of the brain, which is followed by an increase in the size of the actual head.
Sensory processing is often affected, especially the vestibular system. A high pain threshold is often observed. If speech develops, it is often echolalic but some individuals do grasp some language. With a severely affected person there may be an inability to walk or talk. Genetics
Generally, idic(15) is not inherited; it is said to appear de novo, in one member of the family, by chance. In most cases, the abnormal chromosome is generated in the mothers germ cells: the oocytes. This finding is due to ascertainment bias; cases with maternally derived idic(15) usually have clinical findings and attract attention, but those with paternally derived idic(15) usually do not. Thus, diagnosed cases are usually patients where the duplicated material is derived from the mothers egg cell rather than the fathers sperm cell.People with idic(15) have extra genetic material that has developed from chromosome 15. The material usually exists as a little extra chromosome 15; sometimes called a marker chromosome or an extra structurally abnormal chromosome (ESAC). The marker usually exists as an isodicentric chromosome; i.e. 2 copies of a specific part of the long arm of chromosome 15q11.2-q13.1 that is mirrored and doubled, with 2 centromeres and 2 DNA satellites. The smallest markers appear to be harmless and they may go undetected. However, if they are large enough to contain a number of important genes, they may result in "idic(15) syndrome" which is characterized by learning disabilities, autism and other neurological symptoms.