Neuralgic amyotrophy hereditary (neuralgic amyotrophy Hereditary) - Gen SEPT9
Hereditary neuralgic amyotrophy is a disorder characterized by episodes of severe pain and loss of muscle mass (atrophy) in one or both shoulders and arms. The nerve pain is felt along one or more nerves and often has no obvious physical cause. The nerves involved in hereditary neuralgic amyotrophy are grouped into the brachial plexus that control movement and sensation in the shoulders and arms. People with hereditary neuralgic amyotrophy usually begin to suffer episodes at twenty, but in some cases begin at the age of one year. These episodes may be spontaneous or caused by stress, strenuous exercise, childbirth, surgery, exposure to cold, infections, vaccines or emotional disturbances. Although episodes tend to decrease with age, those affected are often left with residual problems, such as chronic pain and impaired movement, which have accumulated over time.
A typical episode begins with severe pain on one or both sides of the body, most often on the right side. The pain can be difficult to control with medication and usually lasts about a month. Over a period of time may be a few hours to a few weeks, the muscles of the affected begin to weaken and atrophy, and movement becomes difficult. Muscle atrophy can cause changes in the posture of the shoulders, back and arm. In particular, the weakness in the muscles of the shoulders tends to make the blades protrude in the back, known as a sign scapular separation. Additional features of hereditary neuralgic amytrophy may include hypoesthesia and paresthesia.
In some affected families, people with hereditary neuralgic amyotrophy also have unusual physical characteristics such as short stature, skinfold more neck and arms, cleft palate, uvula bifida and partial syndactyly. They may also have distinctive facial features, including ocular hypotelorism, short palpebral fissures with Epicanthal fold, a long nasal bridge, a narrow mouth and facial asymmetry.
This process has been linked to mutations in the gene SEPT9, located on the long arm of chromosome 17 (17q25). This gene encodes a protein called Septin-9, part of a group of proteins called Septins. Septins are involved in the process of cytokinesis (cell division stage). Septin-9 also appears to act as a tumor suppressor, that is, regulates cell growth and prevents cells from dividing too rapidly or uncontrollably. The SEPT9 gene appears to be active in cells throughout the body. They can be coded about 15 isoforms septin-9 protein by this gene. Some types of cells produce certain isoforms, while other types of cells produce other isoforms. However, the specific distribution of these isoforms in body tissues is not well known. Isoforms septin-9 interact with other proteins group Septins to perform some functions.
They have identified several genetic mutations in individuals with hereditary SEPT9 neuralgic amyotrophy. The most common mutation involves the replacement of the amino acid arginine to the amino acid tryptophan at position 88 in the sequence of the Septin-9 protein (Arg88Trp or R88W). This mutation has been identified in several unrelated families from around the world. Duplication of genetic material in the SEPT9 gene has also been identified in affected individuals. Changes in this gene can alter the amino acid sequence in certain isoforms septin-9 so that interfere with its function. These mutations can also change the distribution of isoforms septin-9 and its interactions with other Septins in some of the tissues. This change in the functioning of proteins Septins group seems particularly affect the nerve network that controls movement and sensation in the shoulders and arms (brachial plexus), but the reason is unknown. Because many of the triggers of episodes of hereditary neuralgic amyotrophy also affect the immune system is believed to be an autoimmune reaction step. However, the relationship between mutations of SEPT9 and immune function is unclear. Autoimmune phenomena in the brachial plexus nerves could be responsible for the signs and symptoms of hereditary neuralgic amyotrophy.
Alterations in gene expression SEPT9 are also associated with certain cancers. Thus, the increased production of some isoforms of the Septin-9 protein, has been associated with breast and prostate. This altered expression of genes SEPT9, has also been found in many other cancers, including ovarian tumors, pancreas, lung, kidney, liver, thyroid and esophagus.
This disease is inherited as an autosomal dominant inheritance, which means that a copy of the altered gene in each cell is sufficient to express the alteration.
Tests performed in IVAMI: in IVAMI perform detection of mutations associated with hereditary neuralgic amyotrophy, by complete PCR amplification of exons SEPT9 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).