Charcot–Marie–Tooth disease

The Charcot -Marie -Tooth (CMT ) was named after their discoverers, Jean -Martin Charcot ( 1825-1893 ), Pierre Marie ( 1853-1940 ) and Howard Tooth ( 1856-1926 ). Today, the term hereditary motor and sensory neuropathy type I ( HMSN I) is more common. It is also called Neural muscle atrophy and is one of the neuromuscular diseases.

Epidemiology

The Charcot -Marie -Tooth disease is the most common neurogenetic disease. 20-30 people per 100,000 are affected. It is in most cases an autosomal dominantly inherited disease, so there are clusters within individual families. In most cases, the CMT is caused by a mutation on chromosome 17.

Etiology

CMT is an inherited disease of the peripheral nerves, in which a genetic mutation called by either the nerve cell process, axon, or the insulating myelin sheath is damaged. The myelin could be compared with the plastic insulation around an electric cable. It is hampered in the peripheral nerves, so that the commands of the brain can not properly reach the muscles, the saltatory conduction, ie, the transmission of nerve impulses. From denervation followed by a weakness and a loss of the affected muscles.

Unlike the muscular dystrophies the people who have CMT are born with normal muscle. The muscles shrink ( atrophy ) because the affected nerves of CMT can not be transferred exactly the commands of the brain for specific muscle movements.

The primary defect is in a doubling of the PMP (Peripheral myelin protein) gene on chromosome 17 This initially leads to thickening of the myelin sheaths. In the long run the myelin sheath and / or the axon is damaged, probably by impeding the supply of nutrients. The stronger the myelin sheath is damaged, the lower the nerve and the more severe the severity of the disease. Normal is a nerve of 50 m / s In the demyelinating form is a conduction velocity of < 38 m / sec, in the axonal form of > before 38 m / sec.

Symptoms

The disease often begins in childhood. But sometimes there are also only between 20 and 30 years of age to first manifestations. The main symptoms of this disease consist in an increasing weakness of the hands and feet that spreads gradually in the arms and legs. Sometimes the individuals concerned have only the aid of crutches or even a life in a wheelchair.

In general, the tibialis is affected anterior ( dorsiflexors ) that runs down the front of the shin as the first muscle. This results in an unsteady gait: The foot hangs limply, one stumbles slightly and the leg has to increase from the thigh to the toes loose from the floor. The foot is patschend back onto the floor. This is clearly referred to as a stepper or a stork.

The reflexes, especially the Achilles tendon reflex, fall out prematurely.

Diagnosis

The measurement of the ( much reduced ) nerve and the nerve biopsy support the diagnosis. Meanwhile, in addition, a genetic test to identify the underlying mutation is possible. There is not a causal treatment.

Course and prognosis

With long-term course of the atrophy of the lower leg muscles is apparent at first sight, the lower leg act gracefully, while the thigh muscles may still be strongly developed. Sensible irritative symptoms (pain, discomfort, muscle spasm ) part of the symptoms. However, the motor deficits are more pronounced and determine the clinical picture. The atrophy of the muscles below approximately symmetrically above. Overall, the course is very slow and takes decades to. A cure for genetic disease is not yet possible.