Congenital insensitivity to pain

Congenital insensitivity to pain is most commonly caused by changes (mutations) in the SCN9A gene. This gene provides instructions for making one part (the alpha subunit) of a sodium channel called NaV1.7. Sodium channels play an important role in making and sending electrical signals. The NaV1.7 sodium channels are found in nerve cells called nociceptors that transmit pain signals to the spinal cord and brain.

In people affected with congenital insensitivity to pain, the gene changes (mutations) in SCN9A cause the alpha subunits to be nonfunctional; therefore, the NaV1.7 channels cannot be formed. The absence of NaV1.7 channels means that pain signals cannot be sent from the injury site to the brain, causing those affected to be insensitive to pain.

In rare cases, congenital insensitivity to pain may be caused by changes (mutations) in the PRDM12 gene. This gene is involved in the formation of sensory neurons.

Siblings of an individual affected with congenital insensitivity to pain (CIP) have a 25% (1 in 4) chance of being affected if the gene responsible is inherited in an autosomal recessive pattern. Genetic testing is recommended for siblings of a child with CIP. Genetic testing should also be considered by siblings of the affected person’s parents (aunts and uncles), since they can be carriers. Carriers have one abnormal copy of a gene associated with CIP, whereas those who are affected have two abnormal copies. Carriers do not typically show symptoms of this condition, but they may have a chance of having children with CIP if their partner is also a carrier.

If a parent is affected, the other parent should have genetic testing to determine whether he or she is a carrier. If the other parent is a carrier for an abnormal copy of a gene for CIP, then their children could either be carriers or affected with CIP. If the other parent is not a carrier, then all of the couple’s children will still be carriers.

In rare cases where CIP is inherited in an autosomal dominant manner, the siblings of an affected individual are at 50% risk to have also inherited the mutation.

A genetic counselor can discuss the inheritance of CIP in your family, the chances of this condition being passed on in a family, and help determine who else in your family should be tested. Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

Individuals with congenital indifference to pain (CIP) should avoid the following.

Congenital insensitivity to pain is a condition, present from birth, that inhibits the ability to perceive physical pain. Affected individuals are unable to feel pain in any part of their body. Over time this lack of pain awareness can lead to an accumulation of injuries and health issues that may affect life expectancy. Congenital insensitivity to pain is caused by mutations (harmful changes) in one of at least 6 genes known to cause pain insensitivity. It is inherited in an autosomal recessive pattern. Congenital insensitivity to pain is considered a form of peripheral neuropathy because it affects the peripheral nervous system, which connects the brain and spinal cord to muscles and to cells that detect sensations such as touch smell and pain. It is part of a group known as hereditary sensory and autonomic neuropathies.

Congenital insensitivity to pain is most commonly caused by abnormal changes (mutations) in the SCN9A gene and PRDM12 gene. There are other genes that are associated with insensitivity to pain. The genes and possible symptoms include the following.

Congenital insensitivity to pain is characterized by the inability to perceive physical pain. People with this condition can feel the difference between sharp and dull and hot and cold but cannot sense for example that a hot beverage is burning their tongue. This condition which is present from birth can lead to an accumulation of wounds, bruises, broken bones and other health issues that may go undetected over time and can lead to a reduction in life expectancy. Young children with congenital insensitivity to pain may have mouth or finger wounds due to self-biting and may also experience multiple burn-related injuries. Many people with this condition also have a complete loss of the sense of smell (anosmia). In cases of congenital insensitivity to pain caused by mutations in the PRDM12 gene the patients have a normal sense of smell, predisposition to infections, and a greater incidence of corneal abrasions due to a lack of tear production. Visit GeneReviews for a table that shows some of the symptoms a person with a gene mutation in these or other genes that cause congenital insensitivity to pain may have.

There is no formal criteria for the diagnosis of congenital insensitivity to pain (CIP). A detailed history should be gathered to understand if a person has an altered perception to pain. In some cases, CIP may be suspected as early as infancy when painful stimuli like the pin prick from blood draw does not provoke a response. It can also be suspected after the first teeth erupt and biting the tongue, lips, or fingers does not seem to cause pain. In older individuals, CIP may be suspected after repeated injuries with no associated pain. Many people with CIP also have complete loss of smell (anosmia).

A clinical exam where a stimulus is applied to test for pain perception is completed. When CIP is suspected based on clinical and history, genetic testing of the genes known to cause CIP also can be performed. Genetic testing involves a simple blood test typically ordered by a medical geneticist or a genetic counselor after an assessment is done to determine if an individual has health problems that sounds like CIP or another genetic condition. A primary care provider may assist in making a referral to a medical geneticist/genetic counselor. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website . Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

Genetic testing of the genes known to cause congenital insensitivity to pain (CIP) can confirm a diagnosis. Genetic testing involves a simple blood test typically ordered by a medical geneticist or a genetic counselor after an assessment is done to determine if an individual has health problems that sounds like CIP or another genetic condition. A primary care provider may assist in making a referral to a medical geneticist/genetic counselor. A medical geneticist can be found by asking your doctor for a referral or looking on the American College of Medical Geneticists website . Genetic counselors in the United States can be found on the National Society of Genetic Counselors website. Genetic counselors in Canada can be found at the Canadian Association of Genetic Counselors website.

The following resources can help you find the most current clinical research studies.

Through CenterWatch, you can find clinical trials for neuropathies at http://www.centerwatch.com/clinical-trials/listings/condition/215/neuropathy

Through Clinical Connection, you can search for clinical trials at http://www.neuropathyaction.org/. Type "Neuropathy" in the keyword box.

Through [link url="clinicaltrials.gov” target=”_blank”>clinicaltrials.gov, you can search for clinical trials. Go to https://clinicaltrials.gov/ct2/home, and in the box where it says "Search for Studies", type in "neuropathy"

A medicine called naloxone may temporarily cause pain (CIP) sensation has been suggested for some cases. This can be used to help detect the source of injury or illness in someone with CIP. The risk of this medication is that the person with CIP may suffer widespread pain from multiple accumulated injuries.

Congenital insensitivity to pain cannot be cured. Because affected people do not feel pain, preventing injuries and finding injuries quickly is important. To encourage prompt detection of injuries, patient/parents should conduct daily self-checks particularly of vulnerable regions such as their feet, hands and joints. Doctors should look for broken bones, even if the patient feels no pain. Performing X-rays and other imaging tests at sites of possible injury is recommended. An annual skeletal MRI may also be recommended.

Patients are at increased risk of repeated Staphylococcal infections that arise without an obvious external cause. The early use of topical antibacterial creams until all signs of inflammation or infection have resolved has shown to be highly effective in preventing chronic infection.

Some individuals with CIP have a greater incidence of corneal abrasions (eye problem). Management includes at least yearly ophthalmological assessments, regular use of eye lubricants during the day and at night, eye protection in windy or dusty conditions and the avoidance of irritants and chemicals.

Since 1932, about 50 cases of congenital indifference to pain have been reported. Fewer than 1 in 1,000,000 are affected.

Congenital insensitivity to pain (CIP) is inherited within families in an autosomal recessive pattern in most cases, which means that both copies of the gene responsible for CIP in a person need to be changed or mutated. The parents of an individual with CIP each carry one copy of the changed or mutated gene and one normal copy, so they typically do not show signs of the disease. A person with CIP inherits the changed or mutated gene from each parent, so that both copies of their CIP gene do not work properly.
If parents have one child with CIP, there is a 1 in 4 or 25% risk that each future child will also have CIP.

One exception is mutations in the SCN11A gene, which is inherited in an autosomal dominant manner. In autosomal dominant inheritance, only one copy a the gene has to have a mutation to cause CIP. The risk that a person with CIP would have a child with CIP is 1 in 2 or 50% in these cases.

Giving money to help research congenital insensitivity to pain happens through supporting the larger group of conditions called neuropathies (conditions that affect nerves).

You can donate to the Foundation for Peripheral Neuropathy at https://www.foundationforpn.org/. Click on "Donate Now!" on the right side of the page.

You can donate to the Neuropathy Action Foundation at http://www.neuropathyaction.org/. Click on "Support NAF" on the top. Then, on the left side, there are different ways listed to support the Neuropathy Action Foundation.

People with congenital insensitivity to pain may be under the care of several specialists, depending upon their symptoms. Following is a list of some of the specialists that may be needed.

Other names for congenital insensitivity to pain include:

Congenital insensitivity to pain falls in a family of conditions called Hereditary Sensory and Autonomic Neuropathies. Congenital insensitivity to pain can look similar to congenital insensitivity to pain with anhidrosis and hereditary sensory and autonomic neuropathy type 2D (HSAN2D). Congenital insensitivity to pain with anhidrosis is a more severe condition that causes brain damage, mental retardation, and fevers in addition to not feeling pain. Patients with HSAN2D tend not to feel pain only in hands, feet, and parts of the legs. Hearing loss also occurs, as well as reduced senses of smell and taste.

There are no support groups specific to congenital insensitivity to pain. However, there are groups that work with people affected by many different types of neuropathies (conditions that affect nerves).