Congenital insensitivity to pain

Overview

Congenital Insensitivity to Pain (CIP), also known as congenital analgesia, is a rare genetic disorder in which a person is unable to perceive physical pain from birth. Individuals with CIP can feel touch and pressure but do not experience pain in response to injury, heat, or internal damage. While this might seem advantageous, the inability to sense pain can lead to serious injuries, infections, and even unnoticed life-threatening conditions. People with CIP often experience bone fractures, burns, and joint damage without awareness due to the absence of protective pain responses.

Causes

CIP is caused by mutations in genes involved in pain signal transmission. The most commonly affected genes include:

• SCN9A: This gene encodes a sodium channel (NaV1.7) critical for pain signaling in peripheral nerves. Mutations here prevent the generation of nerve impulses that transmit pain signals.

• NTRK1: Involved in the development of pain-sensing neurons. Mutations can lead to both insensitivity to pain and inability to sweat (HSAN type IV).

• PRDM12: Plays a role in early pain neuron development. Mutations can disrupt proper formation of these neurons.

CIP is inherited in an autosomal recessive pattern, meaning both parents must carry a copy of the mutated gene for a child to be affected.

Symptoms

The hallmark symptom of CIP is the inability to feel physical pain. Additional signs and complications may include:

• Frequent injuries: Cuts, bruises, burns, or broken bones that go unnoticed

• Oral injuries: Tongue and lip biting, especially in young children

• Bone and joint problems: Repeated injuries may lead to joint deformities and bone infections (osteomyelitis)

• Infections: Due to untreated wounds

• Anhidrosis (in some forms): Inability to sweat, leading to overheating and fever

• Delayed motor development: Due to repeated joint injuries or poor proprioception

• Corneal damage: From lack of blinking or rubbing the eyes excessively

Despite the physical challenges, cognitive development is typically normal unless associated with other syndromic features.

Diagnosis

Diagnosis of CIP is based on clinical presentation and confirmed through genetic testing. The diagnostic process includes:

• Medical history and physical exam: Identification of pain insensitivity and unexplained injuries

• Neurological examination: To confirm intact touch and temperature sensation but absent pain perception

• Quantitative sensory testing (QST): Measures responses to pain, pressure, and temperature

• Genetic testing: Confirms the diagnosis by identifying mutations in SCN9A, NTRK1, or PRDM12

• Nerve biopsy (rarely): May be used in complex or atypical cases to assess nerve fiber density

Treatment

There is currently no cure for CIP. Management focuses on preventing injuries and monitoring for complications. Treatment strategies include:

• Protective measures: Use of helmets, padded clothing, and safe environments to reduce injury risk

• Regular check-ups: Frequent examinations to detect injuries, infections, or bone abnormalities

• Orthopedic support: Bracing or surgery may be required to treat bone deformities or joint damage

• Wound care and infection control: Prompt treatment of injuries and infections

• Eye protection: Lubricating drops and glasses to prevent corneal damage

• Parental education and supervision: Vital for young children to ensure safety and early injury detection

• Genetic counseling: For affected families to understand inheritance and future risks

Prognosis

The prognosis for individuals with Congenital Insensitivity to Pain varies. With careful management and preventive care, many can live into adulthood. However, complications such as infections, bone deformities, and overheating (in cases with anhidrosis) can impact quality of life and lead to early mortality if not managed properly. Early diagnosis, education, and a multidisciplinary care team are key to improving outcomes and promoting a safe, active life.