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 HSAN2A 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 HSAN2A have a reduction in the number of sensory neurons; however, the role that WNK1/HSN2 mutations play in that loss is unclear. HSAN2B is caused by mutations in the RETREG1 gene. These mutations may lead to an abnormally short and nonfunctional protein. The RETREG1 protein is found in sensory and autonomic neurons. It is involved in the survival of neurons, particularly those that transmit pain signals, which are called nociceptive neurons. When the RETREG1 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 autonomic nervous system seen in people with HSAN2. 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 autonomic 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.
In some affected people, the condition may also cause mild abnormalities of the autonomic nervous system, which controls involuntary body functions such as heart rate, digestion, and breathing. The signs and symptoms of HSAN2 typically begin in infancy or early childhood. The first sign of HSAN2 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 HSAN2 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 HSAN2, 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 HSAN2 on the autonomic nervous system are more variable. Some infants with HSAN2 have trouble sucking, which makes it difficult for them to eat. People with HSAN2 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.