Which are the causes of Congenital Insensitivity To Pain With Anhidrosis (CIPA)?

Congenital Insensitivity to Pain with Anhidrosis (CIPA), also known as Hereditary Sensory and Autonomic Neuropathy type IV (HSAN IV), is caused by specific mutations in the NTRK1 gene. This genetic condition disrupts the development of nerve cells responsible for sensing pain, temperature, and regulating sweat production, meaning the cause is entirely hereditary rather than triggered by environmental or lifestyle factors.

What genetic mutations cause CIPA?

The primary cause of Congenital Insensitivity to Pain with Anhidrosis (CIPA) is an autosomal recessive mutation in the NTRK1 gene located on chromosome 1. This gene provides instructions for creating a protein called high-affinity nerve growth factor receptor. When this protein is dysfunctional, the body fails to properly develop small nerve fibers (nociceptors) that transmit pain and temperature signals, as well as the sympathetic neurons that control sweating.

Is CIPA hereditary?

Yes, Congenital Insensitivity to Pain with Anhidrosis (CIPA) follows an autosomal recessive inheritance pattern. This means an individual must inherit two copies of the mutated gene—one from each parent—to manifest the condition. Parents who are carriers of one mutated gene typically do not show symptoms of Congenital Insensitivity to Pain with Anhidrosis (CIPA) themselves but have a 25% chance of passing the condition to each child.

What are the key biological mechanisms?

The pathophysiology of Congenital Insensitivity to Pain with Anhidrosis (CIPA) involves a failure in the maturation of specific sensory and autonomic neurons. The following systems are critically impacted:

• Nociceptive pathways: The inability to sense pain, leading to high risks of self-mutilation and unrecognized injuries.


• Thermoregulatory pathways: Anhidrosis (the inability to sweat) prevents the body from cooling down, leading to recurrent, life-threatening fevers.


• Sympathetic nervous system: Developmental deficiencies in autonomic neurons that regulate heart rate and blood pressure.

Is the cause of CIPA fully understood?

While the genetic etiology of Congenital Insensitivity to Pain with Anhidrosis (CIPA) is well-mapped to the NTRK1 gene, researchers are still investigating why the severity of symptoms varies between individuals with the same mutation. Current research focuses on how these neurological deficits interact with other developmental pathways to influence cognitive outcomes and bone health.

Next steps

• Consult a clinical geneticist for formal diagnostic testing and family counseling.


• Connect with the 6 members of the DiseaseMaps.org community to share experiences regarding daily management.


• Establish a multidisciplinary care team, including a neurologist and a pediatrician, to monitor for unrecognized injuries and hyperthermia.

Medical disclaimer: This content is for informational purposes only and does not constitute professional medical advice, diagnosis, or treatment.

References

• NIH Genetic and Rare Diseases Information Center (GARD): Congenital insensitivity to pain with anhidrosis.


• Orphanet: Hereditary sensory and autonomic neuropathy type IV.


• OMIM (Online Mendelian Inheritance in Man): #256800 - Neuropathy, Hereditary Sensory and Autonomic, Type IV.