PMP22 Gene

Guillain-Barré syndrome is an autoimmune disorder that affects the nerves. Autoimmune disorders occur when the immune system malfunctions and attacks the body's own tissues and organs. In Guillain-Barré syndrome, the immune response damages peripheral nerves, which are the nerves that connect the central nervous system (the brain and spinal cord) to the limbs and organs. Specifically, the immune response affects a particular part of peripheral nerves called axons, which are the extensions of nerve cells (neurons) that transmit nerve impulses. Guillain-Barré syndrome can affect the neurons that control muscle movement (motor neurons); the neurons that transmit sensory signals such as pain, temperature, and touch (sensory neurons); or both. As a result, affected individuals can experience muscle weakness or lose the ability to feel certain sensations.

Muscle weakness or paralysis are the characteristic features of Guillain-Barré syndrome. The weakness often begins in the legs and spreads to the arms, torso, and face and is commonly accompanied by numbness, tingling, or pain. Additional signs and symptoms of the condition include difficulty swallowing and difficulty breathing. Occasionally, the nerves that control involuntary functions of the body such as blood pressure and heart rate are affected, which can lead to fluctuating blood pressure or an abnormal heartbeat (cardiac arrhythmia).

There are several types of Guillain-Barré syndrome, classified by the part of the peripheral nerve involved in the condition. The most common type of Guillain-Barré syndrome is acute inflammatory demyelinating polyradiculoneuropathy (AIDP). In AIDP, the immune response damages myelin, which is the covering that protects axons and promotes the efficient transmission of nerve impulses. In two other types of Guillain-Barré syndrome, acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal neuropathy (AMSAN), the axons themselves are damaged by the immune response. In AMAN, only the axons of motor neurons are damaged. In AMSAN, the axons of sensory neurons are also damaged. Because of sensory nerve damage, affected individuals can lose the ability to sense the position of their limbs and can have abnormal or absent reflexes (areflexia).

Miller Fisher syndrome, another type of Guillain-Barré syndrome, involves cranial nerves, which extend from the brain to various areas of the head and neck. Miller Fisher syndrome is characterized by three features: weakness or paralysis of the muscles that move the eyes (ophthalmoplegia), problems with balance and coordination (ataxia), and areflexia. People with this condition can have other signs and symptoms common in Guillain-Barré syndrome, such as muscle weakness.

Guillain-Barré syndrome occurs in people of all ages. The development of the condition usually follows a pattern. Prior to developing the condition, most people with Guillain-Barré syndrome have a bacterial or viral infection. The first phase of Guillain-Barré syndrome, during which signs and symptoms of the condition worsen, can last up to four weeks, although the peak of the illness is usually reached in one to two weeks. During the second phase, called the plateau, signs and symptoms of Guillain-Barré syndrome stabilize. This phase can last weeks or months. During the recovery phase, symptoms improve. However, some people with Guillain-Barré syndrome never fully recover and can still experience excessive tiredness (fatigue), muscle weakness, or muscle pain.

Hereditary neuropathy with liability to pressure palsies is a disorder that affects peripheral nerves. These nerves connect the brain and spinal cord to muscles and sensory cells that detect touch, pain, and temperature. In people with this disorder, the peripheral nerves are unusually sensitive to pressure, such as the pressure that occurs when carrying heavy grocery bags, leaning on an elbow, or sitting without changing position, particularly with crossed legs. These activities would not normally cause sensation problems in people without the disorder.

Hereditary neuropathy with liability to pressure palsies is characterized by recurrent episodes of numbness, tingling, and loss of muscle function (palsy) in the region associated with the affected nerve, usually an arm, hand, leg, or foot. An episode can last from several minutes to several months, but recovery is usually complete. Repeated incidents, however, can cause permanent muscle weakness or loss of sensation. This disorder is also associated with pain in the limbs, especially the hands.

A pressure palsy episode results from pressure on a single nerve, and any peripheral nerve can be affected. Although episodes often recur, they can affect different nerves. The most common problem sites involve nerves in the wrists, elbows, and knees. The fingers, shoulders, hands, feet, and scalp can also be affected. Many people with this disorder experience carpal tunnel syndrome, which occurs when a nerve in the wrist (the median nerve) is involved. Carpal tunnel syndrome is characterized by numbness, tingling, and weakness in the hand and fingers. An episode in the hand may affect fine motor activities such as writing, opening jars, and fastening buttons. An episode of nerve compression in the knee can lead to a condition called foot drop, which makes walking, climbing stairs, or driving difficult or impossible.

The symptoms of hereditary neuropathy with liability to pressure palsies usually begin during adolescence or early adulthood but may develop anytime from childhood to late adulthood. Symptoms vary in severity; many people never realize they have the disorder, while some people experience prolonged disability. Hereditary neuropathy with liability to pressure palsies does not affect life expectancy.

Charcot-Marie-Tooth disease encompasses a group of disorders called hereditary sensory and motor neuropathies that damage the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound. Damage to the peripheral nerves that worsens over time can result in alteration or loss of sensation and wasting (atrophy) of muscles in the feet, legs, and hands.

Charcot-Marie-Tooth disease usually becomes apparent in adolescence or early adulthood, but onset may occur anytime from early childhood through late adulthood. Symptoms of Charcot-Marie-Tooth disease vary in severity and age of onset even among members of the same family. Some people never realize they have the disorder because their symptoms are so mild, but most have a moderate amount of physical disability. A small percentage of people experience severe weakness or other problems which, in very rare cases, can be life-threatening. In most affected individuals, however, Charcot-Marie-Tooth disease does not affect life expectancy.

Typically, the earliest symptoms of Charcot-Marie-Tooth disease result from muscle atrophy in the feet. Affected individuals may have foot abnormalities such as high arches (pes cavus), flat feet (pes planus), or curled toes (hammer toes). They often have difficulty flexing the foot or walking on the heel of the foot. These difficulties may cause a higher than normal step (steppage gait) and increase the risk of ankle injuries and tripping. As the disease worsens, muscles in the lower legs usually weaken, but leg and foot problems rarely require the use of a wheelchair.

Affected individuals may also develop weakness in the hands, causing difficulty with daily activities such as writing, fastening buttons, and turning doorknobs. People with Charcot-Marie-Tooth disease typically experience a decreased sensitivity to touch, heat, and cold in the feet and lower legs, but occasionally feel aching or burning sensations. In rare cases, affected individuals have loss of vision or gradual hearing loss that sometimes leads to deafness.

There are several types of Charcot-Marie-Tooth disease, which are differentiated by their effects on nerve cells and patterns of inheritance. Type 1 (CMT1) is characterized by abnormalities in myelin, the fatty substance that covers nerve cells, protecting them and helping to transmit nerve impulses. These abnormalities slow the transmission of nerve impulses and can affect the health of the nerve fiber. Type 2 (CMT2) is characterized by abnormalities in the fiber, or axon, that extends from a nerve cell body to muscles or to sense organs. These abnormalities reduce the strength of the nerve impulse. In forms of Charcot-Marie-Tooth disease classified as intermediate type, the nerve impulses are both slowed and reduced in strength, probably due to abnormalities in both myelin and axons. Type 4 (CMT4) is distinguished from the other types by its pattern of inheritance; it can affect either the axons or the myelin. Type X Charcot-Marie-Tooth disease (CMTX) is caused by mutations in genes on the X chromosome, one of the two sex chromosomes. Within the various types of Charcot-Marie-Tooth disease, subtypes (such as CMT1A, CMT1B, CMT2A, CMT4A, and CMTX1) indicate different genetic causes.

Sometimes other, historical names are used to refer to particular forms of Charcot-Marie-Tooth disease. For example, Roussy-Levy syndrome is a form of CMT11 with the additional feature of rhythmic shaking (tremors). Dejerine-Sottas syndrome is a term sometimes used to describe a severe, early childhood form of Charcot-Marie-Tooth disease; it is also sometimes called type 3 (CMT3). Depending on the specific gene that is altered, this severe, early-onset form of the disorder may also be classified as CMT1 or CMT4. CMTX5 is also known as Rosenberg-Chutorian syndrome.