Polymicrogyria (polymicrogyria) - Gen GPR56.
Polymicrogyria is a disorder characterized by abnormal brain development before birth. In people with polymicrogyria, the brain has too many small convolutions. This disease can affect part or whole brain. Sometimes polymicrogyria is unilateral, affecting only a brain lobe, while at other times it is bilateral, affecting both hemispheres. Signs and symptoms of polymicrogyria depend on the surface and regions of the brain that are affected. The mildest form is called unilateral focal Polymicrogyria, which affects a relatively small area of the cerebral hemisphere. In this way minor neurological problems may occur such as mild seizures that can be easily controlled with medication. Bilateral forms often cause severe neurological problems, including epilepsy, developmental delay, crossed eyes, problems with speech and swallowing, and muscle weakness or paralysis. The most severe form of the disease, known as generalized bilateral polymicrogyria affects the whole brain, and causes profound mental retardation, problems with movement, and seizures that are difficult or impossible to control with medication.
In most people with polymicrogyria, the cause of the condition is unknown. However, we have identified several environmental and genetic factors may be responsible. Environmental causes of Polymicrogyria include certain infections during pregnancy and lack of fetal oxygenation. The genetic causes of polymicrogyria may reside in genetic deletions or rearrangements of several different chromosomes. Mutations have been identified in the GPR56 gene, located on the long (q) arm of chromosome 16 (16q13) encoding important for the normal development of the outer layer of the brain protein. This protein interacts with other cell surface proteins to trigger a series of chemical signals within the cell.
They have identified at least 11 mutations in the GPR56 gene causing bilateral frontoparietal Polymicrogyria (BFPP). Most of the identified mutations change a single amino acid in the GPR56 protein, and interfere with normal protein processing. The abnormal protein is trapped inside the cell, where it is unable to reach the cell surface to perform their normal functions signaling. A loss of function probably disrupts the normal migration of neurons during brain development. As a result, the frontal and parietal lobes develop brain abnormalities characteristic of the disease.
This disease can have different patterns of inheritance. The bilaterally, associated with mutations in the GPR56 gene has an autosomal recessive inheritance pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease. Polymicrogyria can also have a pattern of autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to cause the disorder. Other forms of polymicrogyria seem to have an X - linked inheritance pattern. Some people with polymicrogyria have relatives with the disease, while other affected individuals have no family history of the disease. When an individual is the only person affected in your family, it can be difficult to determine the cause and pattern of inheritance of the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Polymicrogyria, by complete PCR amplification of GPR56 gene exons and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).