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.
This mutation behaves inconsistently, however. Some cells produce near normal amounts of the protein, and other cells—particularly brain cells—have very little of the protein. Critical activities in brain cells are probably disrupted by reduced amounts or the absence of IKAP protein, leading to the signs and symptoms of familial dysautonomia. Type 4, Congenital insensitivity to pain with anhidrosis
Congenital insensitivity to pain with anhidrosis (CIPA), also known as hereditary sensory and autonomic neuropathy type IV (HSAN IV), is characterized by insensitivity to pain, anhidrosis (the inability to sweat), and intellectual disability. The ability to sense all pain (including visceral pain) is absent, resulting in repeated injuries including: oral self-mutilation (biting of tongue, lips, and buccal mucosa); biting of fingertips; bruising, scarring, and infection of the skin; multiple bone fractures (many of which fail to heal properly); and recurrent joint dislocations resulting in joint deformity. Sense of touch, vibration, and position are normal. Anhidrosis predisposes to recurrent febrile episodes that are often the initial manifestation of CIPA. Hypothermia in cold environments also occurs. Intellectual disability of varying degree is observed in most affected individuals; hyperactivity and emotional lability are common. Hereditary sensory neuropathy type IV (HSN4) is a rare genetic disorder characterized by the loss of sensation (sensory loss), especially in the feet and legs and, less severely, in the hands and forearms. The sensory loss is due to abnormal functioning of small, unmyelinated nerve fibers and portions of the spinal cord that control responses to pain and temperature as well as other involuntary or automatic body processes.