Eight different clinical entities have been described under<unk> es – all characterized by progressive loss of function that predominantly affects the peripheral sensory nerves. Their incidence has been estimated to be about 1 in 250,000. Type 1 Hereditary sensory neuropathy type 1 is a condition characterized by nerve abnormalities in the legs and feet (peripheral neuropathy). Many people with this condition have tingling, weakness, and a reduced ability to feel pain and sense hot and cold. Some affected individuals do not lose sensation, but instead feel shooting pains in their legs and feet. As the disorder progresses, the sensory abnormalities can affect the hands, arms, shoulders, and abdomen. Affected individuals may also experience muscle wasting and weakness as they get older, but this varies widely within families. Affected individuals typically get open sores (ulcers) on their feet or hands or infections of the soft tissue of the fingertips (whitlows) that are slow to heal. Because affected individuals cannot feel the pain of these sores, they may not seek treatment right away. Without treatment, the ulcers can become infected and may require amputation of the surrounding area. Albeit rarely, people with hereditary sensory neuropathy type 1 may develop hearing loss caused by abnormalities of the inner ear (sensorineural hearing loss). The signs and symptoms of hereditary sensory neuropathy type 1 typically appear during a person's teens or twenties. While the features of this disorder tend to worsen over time, affected individuals have a normal life expectancy if signs and symptoms are properly treated. Type 1 is the most common form among the 5 types of<unk> . Its historical names include mal perforant du pied, ulcero-mutilating neuropathy, hereditary perforating ulcers, familial trophoneurosis, familial syringomyelia, hereditary sensory radicular neuropathy, among others. This type includes a popular disease Charcot-Marie-Tooth type 2B syndrome (HMSN 2B). that is also named as<unk>  sub-type 1C. Type 1 is inherited as an autosomal dominant trait. The disease usually starts during early adolescence or adulthood. The disease is characterized by the loss of pain sensation mainly in the distal parts of the lower limbs; that is, in the parts of the legs farther away from the center of the body. Since the affected individuals cannot feel pain, minor injuries in this area may not be immediately recognized and may develop into extensive ulcerations. Once infection occurs, further complications such as progressive destruction of underlying bones may follow and may necessitate amputation. In rare cases, the disease is accompanied with nerve deafness and muscle wasting.<unk>  disturbance, if present, appears as anhidrosis, a sweating abnormality. Examinations of the nerve structure and function showed signs of neuronal degeneration such as a marked reduction in the number of myelinated fibers and axonal loss. Sensory neurons lose the ability to transmit signals, while motor neurons has reduced ability to transmit signals. Genes related to<unk>  Type 1: Mutations in the SPTLC1 gene cause hereditary sensory neuropathy type 1. The SPTLC1 gene provides instructions for making one part (subunit) of an enzyme called serine palmitoyltransferase (SPT). The SPT enzyme is involved in making certain fats called sphingolipids. Sphingolipids are important components of cell membranes and play a role in many cell functions. SPTLC1 gene mutations reduce the amount of SPTLC1 subunit that is produced and result in an SPT enzyme with decreased function. A lack of functional SPT enzyme leads to a decrease in sphingolipid production and a harmful buildup of certain byproducts. Sphingolipids are found in myelin, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. A decrease in sphingolipids disrupts the formation of myelin, causing nerve cells to become less efficient and eventually die. When sphingolipids are not made, an accumulation of toxic byproducts can also lead to nerve cell death. This gradual destruction of nerve cells results in loss of sensation and muscle weakness in people with hereditary sensory neuropathy type 1. Type 2, Congenital sensory neuropathy<unk>  type II <unk> 2) is a condition that primarily affects the sensory nerve cells (sensory neurons) which transmit information about sensations such as pain, temperature, and touch. These sensations are impaired in people with<unk> 2. In some affected people, the condition may also cause mild abnormalities of the<unk>  nervous system, which controls involuntary body functions such as heart rate, digestion, and breathing. The signs and symptoms of<unk> 2 typically begin in infancy or early childhood. The first sign of<unk> 2 is usually numbness in the hands and feet. Soon after, affected individuals lose the ability to feel pain or sense hot and cold. People with<unk> 2 often develop open sores (ulcers) on their hands and feet. Because affected individuals cannot feel the pain of these sores, they may not seek treatment right away. Without treatment, the ulcers can become infected and may lead to amputation of the affected area. Unintentional self-injury is common in people with<unk> 2, typically by biting the tongue, lips, or fingers. These injuries may lead to spontaneous amputation of the affected areas. Affected individuals often have injuries and fractures in their hands, feet, limbs, and joints that go untreated because of the inability to feel pain. Repeated injury can lead to a condition called Charcot joints, in which the bones and tissue surrounding joints are destroyed. The effects of<unk> 2 on the<unk>  nervous system are more variable. Some infants with<unk> 2 have trouble sucking, which makes it difficult for them to eat. People with<unk> 2 may experience episodes in which breathing slows or stops for short periods (apnea); digestive problems such as the backflow of stomach acids into the esophagus (gastroesophageal reflux); or slow eye blink or gag reflexes. Affected individuals may also have weak deep tendon reflexes, such as the reflex being tested when a doctor taps the knee with a hammer. Some people with<unk> 2 experience a diminished sense of taste due to the loss of a type of taste bud on the tip of the tongue called lingual fungiform papillae. Type 2, congenital sensory neuropathy (also historically known as Morvan's disease), is characterized by onset of symptoms in early infancy or childhood. Upper & lower extremities are affected with chronic ulcerations and multiple injuries to fingers and feet. Pain sensation is affected predominantly and deep tendon reflexes are reduced. Autoamputation of the distal phalanges is common and so is neuropathic joint degeneration. The NCV shows reduced or absent sensory nerve action potentials and nerve biopsy shows total loss of myelinated fibers and reduced numbers of unmyelinated fibers. It is inherited as an autosomal recessive condition. Genes related to<unk>  Type 2: There are two types of<unk> 2, called<unk> 2A and<unk> 2B, each caused by mutations in a different gene.<unk> 2A is caused by mutations in the WNK1 gene, and<unk> 2B is caused by mutations in the FAM134B gene. Although two different genes are involved, the signs and symptoms of<unk> 2A and<unk> 2B are the same. The WNK1 gene provides instructions for making multiple versions (isoforms) of the WNK1 protein.<unk> 2A is caused by mutations that affect a particular isoform called the WNK1/HSN2 protein. This protein is found in the cells of the nervous system, including nerve cells that transmit the sensations of pain, temperature, and touch (sensory neurons). The mutations involved in<unk> 2A result in an abnormally short WNK1/HSN2 protein. Although the function of this protein is unknown, it is likely that the abnormally short version cannot function properly. People with<unk> 2A have a reduction in the number of sensory neurons; however, the role that WNK1/HSN2 mutations play in that loss is unclear.<unk> 2B is caused by mutations in the FAM134B gene. These mutations may lead to an abnormally short and nonfunctional protein. The FAM134B protein is found in sensory and<unk>  neurons. It is involved in the survival of neurons, particularly those that transmit pain signals, which are called nociceptive neurons. When the FAM134B protein is nonfunctional, neurons die by a process of self-destruction called apoptosis. The loss of neurons leads to the inability to feel pain, temperature, and touch sensations and to the impairment of the<unk>  nervous system seen in people with<unk> 2. Type 3, Familial dysautonomia Familial dysautonomia is a genetic disorder that affects the development and survival of certain nerve cells. The disorder disturbs cells in the<unk>  nervous system, which controls involuntary actions such as digestion, breathing, production of tears, and the regulation of blood pressure and body temperature. It also affects the sensory nervous system, which controls activities related to the senses, such as taste and the perception of pain, heat, and cold. Familial dysautonomia is also called<unk> , type III. Problems related to this disorder first appear during infancy. Early signs and symptoms include poor muscle tone (hypotonia), feeding difficulties, poor growth, lack of tears, frequent lung infections, and difficulty maintaining body temperature. Older infants and young children with familial dysautonomia may hold their breath for prolonged periods of time, which
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