Congenital Insensitivity To Pain With Anhidrosis

Congenital Insensitivity To Pain With Anhidrosis
Congenital insensitivity to pain with anhidrosis (CIPA) is a rare condition characterized by the inability to feel pain and temperature, and decreased or absent sweating (anhidrosis). This condition is also known as hereditary sensory and autonomic neuropathy type IV. The signs and symptoms of CIPA appear early, usually at birth or during infancy, but with careful medical attention, affected individuals can live into adulthood.
 
An inability to feel pain and temperature often leads to repeated severe injuries. Unintentional self-injury is common in people with CIPA, typically by biting the tongue, lips, or fingers, which may lead to spontaneous amputation of the affected area. In addition, people with CIPA heal slowly from skin and bone injuries. Repeated trauma can lead to chronic bone infections (osteomyelitis) or a condition called Charcot joints, in which the bones and tissue surrounding joints are destroyed.
 
Normally, sweating helps cool the body temperature. However, in people with CIPA, anhidrosis often causes recurrent, extremely high fevers (hyperpyrexia) and seizures brought on by high temperature (febrile seizures).
 
In addition to the characteristic features, there are other signs and symptoms of CIPA. Many affected individuals have thick, leathery skin (lichenification) on the palms of their hands or misshapen fingernails or toenails. They can also have patches on their scalp where hair does not grow (hypotrichosis). About half of people with CIPA show signs of hyperactivity or emotional instability, and many affected individuals have intellectual disability. Some people with CIPA have weak muscle tone (hypotonia) when they are young, but muscle strength and tone become more normal as they get older.

Cause

Mutations in the NTRK1 gene cause CIPA. The NTRK1 gene provides instructions for making a receptor protein that attaches (binds) to another protein called NGFβ. The NTRK1 receptor is important for the survival of nerve cells (neurons).
 
The NTRK1 receptor is found on the surface of cells, particularly neurons that transmit pain, temperature, and touch sensations (sensory neurons). When the NGFβ protein binds to the NTRK1 receptor, signals are transmitted inside the cell that tell the cell to grow and divide, and that help it survive. Mutations in the NTRK1 gene lead to a protein that cannot transmit signals. Without the proper signaling, neurons die by a process of self-destruction called apoptosis. Loss of sensory neurons leads to the inability to feel pain in people with CIPA. In addition, people with CIPA lose the nerves leading to their sweat glands, which causes the anhidrosis seen in affected individuals.

Diagnosis

People with CIPA should receive a complete physical exam. During the patient interview, a clinician should focus on the patient's receptiveness to pain and history of injuries. A biopsy from a person with CIPA may reveal decreased numbers of nerve fibers and a lack of sweat glands. DNA tests may also be performed to confirm the presence of a mutated NTRK1 gene. CIPA may also be diagnosed through Amniotic fluid (prenatal) genetic testing or Chorionic villus sampling (CVS).

Treatment

There is currently no known cure for CIPA. Treatment is instead focused on the management of symptoms and prevention of injury and infection.
 
- Antibiotics may be taken to treat infections.
- Several different types of behavioral therapy are available to help people with CIPA improve their communication and social skills, and strengthen learning abilities and adaptive behaviors. Evidence suggests that behavioral therapy is most effective if it is started early in life.
- Patients with CIPA who suffer from intellectual disabilities must have access to education tailored to their specific strengths and weaknesses.
- Patients with CIPA may benefit from occupational therapy. During sessions, a therapist helps the child learn the skills needed to perform basic daily tasks, such as feeding, dressing, and communicating with others.