Small fiber neuropathy (Small fiber neuropathy) - Genes SCN9A or SCN10A.

The small fiber neuropathy is a disease characterized by episodes of severe pain that usually starts in the feet or hands. However, as a person ages, pain episodes may affect other regions. Some people have a more general principle, with pain throughout the body. Usually the signs and symptoms of small fiber neuropathy begin in adolescence or mid-adulthood and may include hyperalgesia, hypoesthesia reduced to differentiate between hot and cold, urinary or intestinal problems, heart palpitations, dry eyes capacity or mouth, abnormal sweating and orthostatic hypotension (causing dizziness, blurred vision, or fainting). This disease is considered a form of peripheral neuropathy, affecting the peripheral nervous system, connecting the brain and spinal cord to the muscles and the cells that detect sensation like touch, smell , and pain.

This process is due to mutations in the SCN9A and SCN10A genes encoding subunits of sodium channels.

The SCN9A gene, located on the long arm of chromosome 2 (2q24), encoding the alpha subunit of a sodium channel Nav1.7 called. Sodium channels transport sodium ions into cells and play a key role in the ability of a cell to generate and transmit electrical signals. These channels are in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain. The nociceptors are part of the peripheral nervous system, connecting the brain and spinal cord cells that detect sensation like touch, smell , and pain. Nociceptors are mainly involved in the transmission of pain signals. Nociceptors centers, known as the cell bodies are found in the dorsal root ganglion. Axons transmit information retrograde dorsal root ganglion, which is then sent to the brain. Nav1.7 sodium channels are also found in olfactory sensory neurons. Mutations in the SCN9A gene are responsible for about 30% of cases of small fiber neuropathy. These mutations change individual amino acids in the alpha subunit of the sodium channel Nav1.7. As a result of the altered alpha subunit, the sodium channel will not close when deactivated, allowing sodium ions to flow abnormally in nociceptors. This increase in sodium ions improves the transmission of pain signals and eventually causes the degeneration of axons. Although the reason for this degeneration is unknown, probably it leads to signs and symptoms such as loss of temperature discrimination.

The SCN10A gene, located on the short arm of chromosome 3 (3p22.2), belongs to a family of genes encoding sodium channel. These channels, which transport sodium ions into cells, play a key role in the ability of a cell to generate and transmit electrical signals. The SCN10A gene encoding the alpha subunit of the sodium channel NaV1.8. As Nav1.7 sodium channel, Nav1.8 the channels are in nociceptors that transmit pain signals. In addition to nociceptors, Nav1.8 sodium channels have also been found in heart muscle cells which, by controlling the flow of sodium ions, probably play a role in maintaining a normal cardiac rhythm. Mutations in the gene SCN10A are responsible for about 5% of cases of small fiber neuropathy. These mutations change in the alpha subunit of the sodium channel NaV1.8. Many of the mutations result Nav1.8 sodium channels that open more easily than usual, which increases the flow of sodium ions producing nerve impulses inside nociceptors. This increase in sodium ions improves the transmission of pain signals and eventually causes the degeneration of axons. Although the reason for this degeneration is unknown, probably it leads to signs and symptoms such as loss of temperature discrimination.

The small fiber neuropathy is inherited in an autosomal dominant, which means that a copy of the altered gene SCN9A or SCN10A in each cell is sufficient for the disease to be expressed. In some cases, an affected person inherits the mutation from an affected parent. Other cases are due to new mutations in the gene and occur in people with no history of disease in your family.

Tests in IVAMI: in IVAMI perform detection of mutations associated with small fiber neuropathy, by complete PCR amplification of the exons of the SCN9A and SCN10A genes, respectively, 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).