Hereditary neuropathies affect the peripheral nerves, causing subtle symptoms that worsen gradually.
Hereditary neuropathies may affect only motor nerves (motor neuropathies), only sensory nerves (sensory neuropathies), or both sensory and motor nerves (sensorimotor neuropathies). Motor nerves control muscle movement, and sensory nerves carry sensory information—about such things as pain, temperature, and vibration—to the brain. Some hereditary neuropathies are relatively common but often are not recognized. Hereditary sensory neuropathies are especially rare. These neuropathies tend to impair the ability to sense pain and temperature.
The genes responsible for many hereditary neuropathies have been identified. They include some forms of Charcot-Marie-Tooth disease, Refsum disease (see Other Rare Hereditary Disorders of Lipid Metabolism), porphyria (see Overview of Porphyria), Fabry disease (see Fabry's Disease), and hereditary neuropathy with liability to pressure palsies.
Charcot-Marie-Tooth disease (peroneal muscular atrophy) is a hereditary neuropathy in which the muscles of the lower legs become weak and waste away (atrophy).
Charcot-Marie-Tooth disease is the most common hereditary neuropathy, affecting 1 of 2,500 people. It is a sensorimotor neuropathy. That is, it affects motor nerves (which control muscle movement) and sensory nerves (which carry sensory information to the brain).
There are two main types and several subtypes of the disease. In some types, axons (the part of the nerve that sends messages) remain alive, but the myelin sheath surrounding them is damaged or destroyed (demyelinated). (The myelin sheath functions much like insulation around electrical wires, enabling nerve impulses to travel quickly—see Fig. 1: Insulating a Nerve Fiber.) In other types, the axons die. Most types of the disease are inherited as an autosomal (not sex-linked) dominant trait. That is, only one gene from one parent is required for the disease to develop.
Symptoms vary by type of the disease.
Symptoms begin in middle childhood. Weakness begins in the lower legs. It causes an inability to flex the foot (footdrop) and wasting away of the calf muscles (stork leg deformity). Later, hand muscles begin to waste away. The hands and feet become unable to sense vibration, pain, and temperature, and this loss of sensation gradually moves up the limbs.
In milder subtypes of type 1, high arches and hammer toes may be the only symptoms. In one subtype, males have severe symptoms, and females have mild symptoms or may be unaffected.
The disease progresses slowly and does not affect life span.
The neuropathy progresses more slowly and causes somewhat similar symptoms, often beginning during the teenage years.
Diagnosis and Treatment
The distribution of weakness, the age at which the disease began, the family history, the presence of foot deformities (high arches and hammer toes), and the results of nerve conduction studies help doctors identify the different types of Charcot-Marie-Tooth disease and distinguish them from other causes of neuropathy. Genetic testing and counseling for Charcot-Marie-Tooth disease are available.
No treatment can stop the progression of the disease. Wearing braces helps correct footdrop, and sometimes orthopedic surgery is needed to stabilize the foot. Physical therapy (to strengthen muscles) and occupational therapy may be helpful.
Hereditary Neuropathy With Liability to Pressure Palsies
Hereditary neuropathy with liability to pressure palsies is a hereditary disorder in which nerves become very sensitive to pressure, injury, and use.
In this neuropathy, nerves are susceptible to damage resulting from relatively slight pressure or injury or from repetitive use. Usually, this neuropathy starts during adolescence or young adulthood, but it may start at any age. It affects both sexes equally. It is inherited as an autosomal (not sex-linked) dominant trait. That is, only one gene from one parent is required for the disease to develop.
Peroneal nerve palsy with footdrop, ulnar nerve palsy, and carpal tunnel syndrome (see Carpal Tunnel Syndrome) commonly develop. Numbness or weakness occurs periodically in the affected area. Symptoms vary from unnoticeable and mild to severe and incapacitating. Episodes may last several minutes to months.
Doctors may have difficulty diagnosing this neuropathy because the symptoms come and go. Electromyography and genetic testing help establish the diagnosis. Rarely, biopsy of a nerve is required.
Activities that cause symptoms should be avoided or modified. Supports, such as wrist splints and elbow pads, can reduce pressure, prevent reinjury, and allow the nerve to repair itself over time. Rarely, surgery is needed.
About half of the people who have symptoms recover completely within days to months. In people who do not recover completely, symptoms are rarely severe.
Last full review/revision September 2012 by Michael Rubin, MDCM