What is 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 a rare genetic disorder characterized by the inability to feel pain or temperature and a total lack of sweat production. Because individuals with Congenital Insensitivity to Pain with Anhidrosis (CIPA) cannot sense physical injury, they are at high risk for recurrent self-mutilation, bone fractures, and life-threatening hyperthermia.

What are the primary symptoms of CIPA?

The clinical presentation of Congenital Insensitivity to Pain with Anhidrosis (CIPA) involves a triad of symptoms: absence of pain perception, anhidrosis (inability to sweat), and intellectual disability. Without the warning signal of pain, patients often suffer from:

• Recurrent skin infections and ulcerations.


• Bone fractures that go unnoticed, leading to joint deformities or osteomyelitis.


• Severe, unexplained fevers due to an inability to regulate body temperature through sweating.


• Self-mutilation, particularly biting of the tongue, lips, or fingertips, often starting in infancy.

What causes Congenital Insensitivity to Pain with Anhidrosis (CIPA)?

Congenital Insensitivity to Pain with Anhidrosis (CIPA) is an autosomal recessive disorder caused by mutations in the NTRK1 gene. This gene is responsible for producing a protein essential for the survival and development of nerve cells (neurons) that transmit pain, temperature, and touch signals. When these neurons fail to develop properly, the body’s sensory pathways are essentially "disconnected."

How rare is this condition and who is affected?

Congenital Insensitivity to Pain with Anhidrosis (CIPA) is extremely rare, with fewer than 100 cases documented in medical literature globally. It affects both males and females equally and is typically present at birth. While it occurs worldwide, it is often identified in infancy when caregivers notice a lack of reaction to vaccinations or injuries and the absence of sweat despite high environmental temperatures.

How does CIPA differ from other sensory neuropathies?

Unlike other forms of Hereditary Sensory and Autonomic Neuropathy (HSAN), Congenital Insensitivity to Pain with Anhidrosis (CIPA) is specifically distinguished by the presence of anhidrosis and the associated cognitive delays. While other neuropathies may involve sensory loss, the complete systemic absence of thermal regulation is the hallmark that defines this specific subtype.

Next steps

• Consult a neurologist or clinical geneticist for formal diagnostic testing, including NTRK1 gene sequencing.


• Implement rigorous daily skin and joint inspections to catch injuries early.


• Connect with the Congenital Insensitivity to Pain with Anhidrosis (CIPA) community at DiseaseMaps.org to share experiences with the 6 members currently registered.


• Work with a multidisciplinary team, including physical therapists and pain management specialists, to create a protective care plan.

Medical disclaimer: This information is for educational purposes only and does not replace professional medical advice, diagnosis, or treatment.

References

• National Institutes of Health (NIH) Genetic and Rare Diseases Information Center (GARD).


• Orphanet: Portal for rare diseases and orphan drugs.


• Online Mendelian Inheritance in Man (OMIM): Entry #256800.


• PubMed: Clinical literature on HSAN type IV pathophysiology.