Tibial muscular dystrophy (Tibial muscular dystrophy) - Gen TTN.

Tibial muscular dystrophy is a condition that affects the muscles of the lower front leg. Signs and symptoms of this disease usually appear after 35 years. The first sign is usually weakness and atrophy of the tibialis anterior. This muscle helps control the movement of the foot up and down. Weakness in the tibialis anterior muscle makes it difficult or impossible to walk on his heels but usually does not interfere significantly with normal walks. Muscle weakness gets worse very slowly. 10 to 20 years after the onset of symptoms, weakness may develop in the toe extensors. The weakness in these muscles, makes it difficult to lift the toes when walking, an alteration known as foot drop. Later, about one - third of people with tibial muscular dystrophy have trouble walking due to weakness in other muscles of the legs. However, most affected individuals are still able to walk throughout their lives.

A small percentage of people with tibial muscular dystrophy has a somewhat different pattern of signs and symptoms described above. In this case, from childhood, these individuals may have generalized muscle weakness, weakness and atrophy of the quadriceps or other muscles of the legs and weakness that affects the muscles of the arms.

This disease is due to mutations in the TTN gene, located on the long arm of chromosome 2 (2q31). This gene encodes a protein called titin. This protein plays an important role in skeletal and cardiac muscles. Within muscle cells, titin is an essential component of the sarcomere. Sarcomeres consist of proteins that generate the necessary mechanical strength for the muscles to contract. Titin protein has several functions within the sarcomeres. One of its most important tasks is to provide structure, flexibility and stability to these cellular structures. In addition, it also plays a role in chemical signaling and assembly of new sarcomeres.

Several mutations have been identified in the TTN gene that alter the structure and function of titin. It is believed that these changes may alter interactions with other proteins titin within sarcomeres. Mutations can also interfere with protein function in chemical signaling. An altered protein titin affects normal muscle contraction, which causes the muscles to weaken and corrode over time. It is unclear why these effects are generally limited to the leg muscles.

This disease is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to cause disease. In most cases, an affected person has a parent with the disorder.

Tests in IVAMI: in IVAMI perform detection of mutations associated with tibial muscular dystrophy, by complete PCR amplification of the exons of the gene TTN, 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).