Congenital insensitivity to pain with anhidrosis (CIPA) is a rare genetic disorder characterized by a complete inability to feel pain or temperature, coupled with a decreased or absent ability to sweat. It is also known as hereditary sensory and autonomic neuropathy type IV (HSAN IV). Signs of CIPA emerge early in life, often at birth or during infancy. The condition has an estimated incidence of 1 in 25,000 in some populations.
The Nature of CIPA: Absence of Pain and Sweat
Individuals with CIPA experience a loss of pain and temperature sensation, which can lead to repeated injuries. They cannot feel the warning signals that protect most people from harm, such as the pain from cuts, burns, or fractures. This lack of pain perception means injuries often go unnoticed for prolonged periods, leading to complications like chronic bone infections (osteomyelitis) or joint destruction, known as Charcot joints. Unintentional self-injury is also common, with affected individuals sometimes biting their tongue, lips, or fingers, which can result in spontaneous amputation.
Anhidrosis, the inability to sweat, prevents the body from cooling itself effectively. This impairment in temperature regulation leads to recurrent episodes of high fevers, a condition called hyperpyrexia. These high body temperatures can trigger seizures, known as febrile seizures, posing a significant risk, especially in young children. The combination of pain insensitivity and anhidrosis creates a dangerous environment, as the body lacks its natural defense mechanisms against both external harm and internal overheating.
The Genetic Roots of CIPA
CIPA is an inherited disorder, passed down in an autosomal recessive pattern. This means a child must inherit two copies of the mutated gene—one from each parent—to develop the condition. If a child inherits only one copy, they are a carrier but do not show symptoms.
The underlying cause of CIPA is a mutation in the NTRK1 gene. This gene provides instructions for making a receptor protein that binds to nerve growth factor beta (NGFβ). Mutations in the NTRK1 gene result in a protein that cannot transmit these signals properly, leading to the self-destruction (apoptosis) of sensory neurons and nerves leading to sweat glands. This causes the inability to feel pain and temperature, and anhidrosis.
Navigating Life with CIPA
Living with CIPA presents ongoing challenges that require constant vigilance and a multidisciplinary approach. The absence of pain sensation necessitates continuous monitoring to prevent unnoticed injuries, such as burns, deep cuts, or fractures. Caregivers must regularly inspect the individual’s body for any signs of injury. Injuries that do occur often heal slowly, increasing the risk of chronic infections and long-term damage to bones and joints.
Managing body temperature is a primary concern due to anhidrosis. Individuals with CIPA can quickly overheat in warm environments or during physical activity, leading to fevers. Strategies include wearing light clothing, staying in cool environments, and using cooling vests or other methods to regulate body temperature. Regular medical check-ups are important to address common complications such as dental problems, given the risk of self-mutilation of the mouth, and to monitor for recurrent infections.
Beyond physical challenges, about half of individuals with CIPA exhibit hyperactivity or emotional instability, and many also have intellectual disability. These neurological aspects further complicate daily life and necessitate specialized educational adaptations and behavioral support. The comprehensive care team for a person with CIPA often includes pediatricians, neurologists, orthopedic surgeons, dentists, physical therapists, and occupational therapists, working together to manage symptoms, prevent complications, and improve quality of life.