Congenital insensitivity to pain with anhidrosis

Congenital insensitivity to pain with anhidrosis (CIPA), also called hereditary sensory and autonomic neuropathy type IV, is an extremely rare inherited disorder of the nervous system which prevents the sensation of pain, heat, cold, or any real nerve-related sensations (including feeling the need to urinate); however, patients can still feel pressure. CIPA is the fourth type of hereditary sensory and autonomic neuropathy (HSAN), known as HSAN IV. (It is also referred to as HSAN Type IV). A person with CIPA cannot feel pain or differentiate even extreme temperatures. "Anhidrosis" means the body does not sweat, and "congenital" indicates that the condition is present from birth.

Clinical description

Charcot joints are shown in this boy with CIPA. His right knee and right ankle are enlarged and distorted. The skin over the medial aspect of the ankle is darkened with a draining wound secondary to superimposed osteomyelitis. There are other areas of trauma and ulcers including a site on the right heel.

People with this disorder are very likely to injure themselves in ways that would normally be prevented by feeling pain. For example, a patient could burn themselves severely and not even notice. The main features of the disorder are lack of pain sensation, painless injuries of the arms, legs, and oral structures, hyperthermia during hot weather because of inability to sweat, syndromic intellectual disability as a result of hyperthermia, infection and scarring of the tongue, lips and gums, chronic infections of bones and joints, bone fractures, multiple scars, osteomyelitis and joint deformities, which may lead to amputation. Other common problems are eye related, such as infection due to the sufferers rubbing them too hard, too frequently or scratching them during sleep. In addition, patients typically lack unmyelinated and small myelinated nerve fibers in the dorsal root ganglion. Both are responsible for transmitting pain signals. In addition, patients' sweat glands are normal in both structure and function, though they lack innervations by small diameter neurons.^[1]

Cause

CIPA is caused by a genetic mutation which prevents the formation of nerve cells which are responsible for transmitting signals of pain, heat, and cold to the brain. The disorder is autosomal recessive. It does not appear to have any particular ethnic distribution, though it is more prevalent in cultures in which intermarriage is an accepted practice.^[2] Overheating kills more than half of all children with CIPA before age 3.

The genetic mutation is in the gene encoding the neurotrophic tyrosine kinase receptor (SCN9A gene).^[3] NTRK1 is a receptor for nerve growth factor (NGF). This protein induces outgrowth of axons and dendrites and promotes the survival of embryonic sensory and sympathetic neurons. The mutation in NTRK1 does not allow NGF to bind properly, causing defects in the development and function of nociceptive reception.^[4]

Diagnosis

Management

CIPA sufferers have to live an extremely cautious life, incorporating numerous controls as part of their daily routine. Every morning it will be necessary to check for bruises, scratches or other injuries that might have taken place during sleeping hours, as it is very common for CIPA patients to injure themselves unknowingly. Temperature measuring must be done constantly, as well as urination control, by setting alarms or other reminders. If any kind of accident is suffered, regardless of its type and severity, CIPA patients must go through a thorough check for compromising injuries. At young ages, permanent surveillance is vital. A lack of awareness of the extreme dangers this condition represents condemns the infant to a complete lack of tools against risk and harmful situations. There are several other procedures a CIPA patient has to undergo in order to live a safe life.

Society

The manga and anime series Loveless features a group of four characters, the Zero, with this condition. Notably, they were genetically engineered to possess it as their creator believed being unable to feel pain would make them better warriors.

In the third season of the TV series House in the episode "Insensitive" (14th episode), the patient (Hannah Morganthal, played by Mika Boorem) suffers from this condition. In the third season of the TV series Grey's Anatomy in the episode "Sometimes a Fantasy", Abigail Breslin's character, Megan Clover, is diagnosed with this condition.

CIPA is examined in an episode of Mystery Diagnosis entitled The Boy Who Never Cried, featuring a boy suffering from the disorder. The boy's condition first emerges after the tip of his tongue ulcerates and is accidentally bitten off by the repeated action of it moving against the his growing incisor teeth.^[5]

In the first season episode "The Courier (No. 85)" of the TV series The Blacklist a criminal transporter (played by Robert Knepper) is diagnosed with congenital anhidrosis.

In the Japanese visual novel Dramatical Murder, the character Noiz suffers from CIPA and participates in the fighting simulation called Rhyme in order to feel the illusion of pain.

Ronald Niedermann is an antagonistic character in Stieg Larsson novel The Girl Who Kicked the Hornets' Nest, a criminal that born with a "rare condition" that makes him unable to feel pain.

In the story Ticci Toby, the title protagonist suffers from multiple diseases he is regularly bullied for, one of them being CIPA.

In a story called "Unique", the main character, Adrian is suffering from CIPA and is bullied for being homosexual as well as having the disorder. As a result of the disorder, he starts to develop low blood cells levels. Being in an extremely unique family and situation, he goes through the story with depression and overcomes being different.

X-Files Episode "Home" 1996, The children of the Peacock family apparently had the disorder as after "playing" outside the mother inspected them of injuries as they did not feel pain. The Peacock family was inbred since around the civil war.

References

Further reading

• Indo, Y; Pagon, RA; Adam, MP; Ardinger, HH; Wallace, SE; Amemiya, A; Bean, LJH; Bird, TD; Ledbetter, N; Mefford, HC; Smith, RJH; Stephens, K (1993). "Congenital Insensitivity to Pain with Anhidrosis". University of Washington, Seattle. PMID 20301726. Retrieved 8 July 2017.

External links