Hereditary neuropathies include a variety of congenital degenerative peripheral neuropathies.
(See also Overview of Peripheral Nervous System Disorders.)
Hereditary neuropathies are classified as
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 (varieties of Charcot-Marie-Tooth disease, also called peroneal muscular atrophy) are the most common; they are usually autosomal dominant disorders but can be X-linked. Type I results from a duplication (extra copy) of the peripheral myelin protein-22 gene (PMP22), located on the short arm of chromosome 17.
Types I and II are characterized by weakness and atrophy, primarily in peroneal and distal leg muscles. Patients often have a family history of neuropathy. Natural history varies: Some patients are asymptomatic and have only slowed conduction velocities (detected on nerve conduction studies); others are more severely affected.
Patients with type I may 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. In one subtype, males have severe symptoms, and females have mild symptoms or may be unaffected.
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.
Hereditary sensory and autonomic neuropathies are rare. Five types have been described.
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.
Hereditary neuropathies may affect motor and sensory nerves, sensory nerves, sensory and autonomic nerves, or only motor nerves.
There are 3 main types, which vary in severity and rate of progression; all begin in childhood.
Use braces to correct footdrop and recommend physical and occupational therapy to help patients maintain function; sometimes orthopedic surgery is needed.