Hereditary neuropathy with pressure palsies -HNPP- (Hereditary liability to pressure neuropathy With palsies) - Gen PMP22


Hereditary neuropathy with pressure palsies, is a disorder that affects the peripheral nerves that connect the brain and spinal cord to muscles and sensory cells that detect touch, pain and temperature. In people with this disorder, peripheral nerves are unusually sensitive to pressure.

Symptoms usually start during adolescence or early adulthood, but can develop at any time from childhood to late adulthood and include recurrent episodes of numbness, tingling and / or paralysis. An episode can last from several minutes to several months, but recovery is usually complete. However, repeated incidents can lead to permanent muscle weakness or loss of sensation. This disease is also associated with pain in the extremities, especially the hands. Any peripheral nerve may be affected by an episode of paralysis occurring more frequently in the nerves of the wrists, elbows and knees. Fingers, shoulders, hands, feet and scalp may also be affected. Many people with this condition suffer from carpal tunnel syndrome is involved when a nerve in the wrist. The disease does not affect life expectancy.

This process is due to mutations in the gene PMP22 (Peripheral myelin protein 22), located on the short arm of chromosome 17 (17p12), or loss of one copy of the gene. This gene encodes the protein of peripheral myelin protein 22. This is in the peripheral nervous system, and is a component of myelin, the protective substance covering the nerves and promotes the efficient transmission of nerve impulses. The protein is primarily produced by Schwann cells that surround and insulate nerves. Inside Schwann cells, the protein plays a crucial role in the development and maintenance of myelin. Studies suggest that the PMP22 protein is particularly important in nerve protection against physical pressure, helping to restore their structure after compression. The PMP22 gene may also play a role in the growth of Schwann cells and the process by which cells mature to perform specific functions. Before becoming part of myelin, the protein is processed and stored in the endoplasmic reticulum and Golgi apparatus in.

Have been described at least 123 mutations in PMP22 gene of which: missense mutations (49), and -splicing- mutations cutting member (8), small deletions (19), small insertions (3), major deletions (20 ), inseciones / higher duplications (18) and complex rearrangements (6). The most frequent in the PMP22 gene mutation causes a loss of one copy of the gene in every cell, which probably decreases the amount of protein peripheral myelin 22 available for the production of myelin, or an abnormally small protein is produced, which rapidly decomposes. Other mutations change one of the amino acids found in proteins peripheral myelin 22 causing unstable protein. A reduction in the amount of stable protein results in the loss of myelin. As a result, some protective myelin sheaths can become unstable, which results in an increased sensitivity to pressure on the nerves.

Hereditary neuropathy with pressure palsies is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with hereditary neuropathy with pressure palsies, by complete PCR amplification of the exons of PMP22 gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).