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Hereditary
neuropathies include a variety of congenital degenerative peripheral
neuropathies.
Hereditary neuropathies are classified as sensorimotor, sensory, or motor (see Peripheral Nervous System and Motor Unit Disorders: Motor Neuron Disorders). Causes of secondary hereditary neuropathies include Refsum's disease, porphyria, and Fabry's disease.
Sensorimotor
neuropathies:
There are 3 main types (I, II, and III); all begin in childhood. Some less common types begin at birth and result in greater disability.
Types
I and II (Charcot-Marie-Tooth disease, peroneal muscular atrophy) are the most common; they are usually autosomal dominant disorders. Type I results from a duplication (extra copy) of the peripheral myelin protein-22 gene (PMP22), located on the short arm of chromosome 17. These disorders are characterized by weakness and atrophy, primarily in peroneal and distal leg muscles. Patients may also have other degenerative disorders (eg, Friedreich's ataxia) or a family history of them. Patients with type I present in middle childhood with footdrop and slowly progressive distal muscle atrophy, causing stork leg deformity. Intrinsic muscle wasting in the hands begins later. Vibration, pain, and temperature sensation decreases in a stocking-glove pattern. Deep tendon reflexes are absent. High pedal arches or hammertoes may be the only signs in family members who are carriers. Nerve conduction velocities are slow, and distal latencies are prolonged. Segmental demyelination and remyelination occur. Enlarged peripheral nerves may be palpated. The disease progresses slowly and does not affect life span. Type II evolves more slowly; weakness usually develops later in life. Patients have relatively normal nerve conduction velocities but low amplitude sensory nerve action potentials and compound muscle action potentials. Biopsies detect axonal (wallerian) degeneration.
Type
III (hypertrophic interstitial neuropathy, Dejerine-Sottas disease), a rare autosomal recessive disorder, begins in childhood with progressive weakness and sensory loss and absent deep tendon reflexes. Although initially it resembles Charcot-Marie-Tooth disease, the motor weakness progresses more quickly. Demyelination and remyelination occur, producing enlarged peripheral nerves and onion bulbs, detected by nerve biopsy.
Sensory
neuropathies:
Hereditary sensory neuropathies are rare. Loss of distal pain and temperature sensation is more prominent than loss of vibratory and position sense. The main complication is foot mutilation due to pain insensitivity, resulting in a high risk of infections and osteomyelitis.
Diagnosis
and Treatment
The characteristic distribution of motor weakness, foot deformities, and family history suggests the diagnosis, which should be confirmed by electrophysiologic testing. Genetic analysis is available, but there are no specific treatments.
Bracing helps correct footdrop; orthopedic surgery to stabilize the foot may help. Physical therapy (to strengthen muscles) and occupational therapy may help; vocational counseling may help prepare young patients maintain vocational skills despite disease progression.
Hereditary
Motor Neuropathy With Liability to Pressure Palsies (HNPP)
In
hereditary motor neuropathy with liability to pressure palsies,
nerves become increasingly sensitive to pressure and stretch.
In hereditary motor neuropathy with liability to pressure palsies (HNPP), nerves lose their myelin sheath and do not conduct nerve impulses normally. Inheritance is usually autosomal dominant. The cause is loss of one copy of peripheral myelin protein-22 gene (PMP22), located on the short arm of chromosome 17. Two copies of the gene are needed for normal function. Incidence of HNPP is estimated to be 2 to 5/100,000.
Usually, symptoms start during adolescence or young adulthood, but they may start at any age. Peroneal nerve palsy with footdrop, ulnar nerve palsy, and carpal tunnel syndrome commonly develop. The pressure palsies can be mild or severe and last from minutes to months. Numbness and weakness occur in affected areas.
HNPP should be suspected in patients with recurrent compression mononeuropathies, multiple mononeuropathy of unknown origin, symptoms suggesting recurrent demyelinating polyneuropathy, or a family history of carpal tunnel syndrome. Electrodiagnostic testing and genetic testing aid in diagnosis; rarely, biopsy is required.
Treatment is symptomatic and involves avoiding or modifying activities that cause symptoms. Wrist splints and elbow pads can reduce pressure, prevent reinjury, and allow the nerve to repair the myelin over time. Surgery is rarely indicated.
Last full review/revision February 2008 by Michael Rubin, MD
Content last modified February 2008
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