Progressive myoclonus epilepsy Unverricht-Lundborg of (Unverricht-Lundborg disease, myoclonus epilepsy rogressive P) - CSTB gene.

The Unverricht-Lundborg disease is a rare inherited form of epilepsy. Usually those affected begin to show signs and symptoms between 6 and 15 years old. This disease is classified as a type of progressive myoclonus epilepsy. Affected individuals have episodes of myoclonus that, over time, increase in frequency and intensity. These episodes may be triggered by physical exercise, stress, light or other stimuli. Eventually, myoclonic episodes can be so intense that interfere with walking and other daily activities. In addition, affected individuals often also have tonic-clonic seizures. Like myoclonic episodes, they may increase in frequency for several years, but can be controlled with treatment. After several years of evolution, the frequency of crises can be stabilized or decreased.

Other signs and symptoms of the disease may include ataxia, involuntary rhythmic tremor that worsens during movement, dysarthria, depression and a slow and slight decrease in intellectual functioning. Individuals with Unverricht-Lundborg disease usually live into adulthood. Depending on the severity of the disorder and a person's response to treatment, life expectancy may be normal.

This process is due to mutations in the CSTB gene, located on the long arm of chromosome 21 (21q22.3). This gene encodes a protein called cystatin B. This protein inhibits the activity of cathepsins, which help break down certain proteins in lysosomes. Although the function of cystatin B is unclear, it is likely to help protect proteins from cells of cathepsins that escape from the lysosome. CSTB gene a region having a particular repeating sequence of 12 nucleotides (CCCCGCCCCGCG). This sequence, called dodecamer repetition, usually repeated two or three times within a portion of the gene that helps regulate protein coding cystatin B.

In almost all those affected, progressive myoclonus epilepsy Unverricht-Lundborg is caused by an increased number of copies of the dodecamer repetition in the CSTB gene. Most affected people are over 30 repetitions of the sequence dodecamer in both copies of the CSTB gene. In a small number of individuals, a copy of the CSTB gene has extended dodecamer repetition while the second contains a copy of the other nine mutations identified. Some of these mutations replaced amino acids in the protein cystatin B. Other mutations result encoding a protein with altered function or nonfunctional. Only one individual with the disease, has been reported to have different mutations expansion dodecamer repetition in both copies of the gene in each repetition enlarged célula.La dodecamer the CSTB gene appears to interfere with the Cystatin B protein coding concentrations cystatin B in affected individuals are only 5% to 10% of normal, and cathepsin concentrations are significantly increased. It is believed that these changes cause the signs and symptoms of the disease , however, the specific mechanism is unknown.

This disease is inherited in an autosomal recessive pattern, that is, 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.

Tests in IVAMI: in IVAMI perform detection of mutations associated with progressive myoclonus epilepsy Unverricht-Lundborg of, by complete PCR amplification of the exons of the CSTB gene 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).