Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neurological
disorders, also known as hereditary motor and sensory neuropathy (HMSN) or peroneal
muscular atrophy, it comprises a group of disorders that affect peripheral nerves.
The peripheral nerves lie outside the brain and spinal cord and supply the muscles
and sensory organs in the limbs.
Symptoms of Charcot-Marie-Tooth Disease The neuropathy
of CMT affects both motor and sensory nerves. A typical feature includes weakness
of the foot and lower leg muscles, which may result in foot drop and a high-stepped
gait with frequent tripping or falls. Foot deformities, such as high arches and hammertoes
(a condition in which the middle joint of a toe bends upwards) are also characteristic
due to weakness of the small muscles in the feet. In addition, the lower legs may
take on an "inverted champagne bottle" appearance due to the loss of muscle bulk.
Later in the disease, weakness and muscle atrophy may occur in the hands, resulting
in difficulty with fine motor skills.
Onset of symptoms is most often in adolescence
or early adulthood, however presentation may be delayed until mid-adulthood. The
severity of symptoms is quite variable in different patients and even among family
members with the disease. Progression of symptoms is gradual. Pain can range from
mild to severe, and some patients may need to rely on foot or leg braces or other
orthopedic devices to maintain mobility. Although in rare cases patients may have
respiratory muscle weakness, CMT is not considered a fatal disease and people with
most forms of CMT have a normal life expectancy.
Causes A nerve cell communicates information
to distant targets by sending electrical signals down a long, thin part of the cell
called the axon. In order to increase the speed at which these electrical signals
travel, the axon is insulated by myelin, which is produced by another type of cell
called the Schwann cell. Myelin twists around the axon like a jelly-roll cake and
prevents dissipation of the electrical signals. Without an intact axon and myelin
sheath, peripheral nerve cells are unable to activate target muscles or relay sensory
information from the limbs back to the brain.
CMT is caused by mutations in genes that produce proteins involved in the structure
and function of either the peripheral nerve axon or the myelin sheath. Although different
proteins are abnormal in different forms of CMT disease, all of the mutations affect
the normal function of the peripheral nerves. Consequently, these nerves slowly degenerate
and lose the ability to communicate with their distant targets. The degeneration
of motor nerves results in muscle weakness and atrophy in the extremities (arms,
legs, hands, or feet), and in some cases the degeneration of sensory nerves results
in a reduced ability to feel heat, cold, and pain.
The gene mutations in CMT disease
are usually inherited. Each of us normally possesses two copies of every gene, one
inherited from each parent. Some forms of CMT are inherited in an autosomal dominant
fashion, which means that only one copy of the abnormal gene is needed to cause the
disease. Other forms of CMT are inherited in an autosomal recessive fashion, which
means that both copies of the abnormal gene must be present to cause the disease.