Congenital insensitivity to pain with anhidrosis

Información en español Title

Other Names:

Neuropathy, congenital sensory, with anhidrosis; CIPA; Hereditary sensory and autonomic neuropathy 4; Neuropathy, congenital sensory, with anhidrosis; CIPA; Hereditary sensory and autonomic neuropathy 4; HSAN 4; Familial dysautonomia, type 2; Insensitivity to pain, congenital, with anhidrosis; Hereditary sensory neuropathy type IV; HSNAN4; HSAN IV; Familial dysautonomia, type II See More

Categories:

Congenital and Genetic Diseases; Nervous System Diseases

Summary Summary

Congenital insensitivity to pain with anhidrosis (CIPA) also known as hereditary sensory and autonomic neuropathy type IV, is an inherited condition characterized by the inability to feel pain and temperature, and decreased or absent sweating (anhidrosis). The signs and symptoms of CIPA usually appear at birth or during infancy. The inability to feel pain and temperature often leads to repeated, severe injuries and unintentional self-injury is common. People with CIPA may also heal slowly from skin and bone injuries, which can lead to chronic bone infections (osteomyelitis) or a condition called Charcot joints. Absent sweating can cause recurrent, high fevers (hyperpyrexia) and seizures brought on by high temperature (febrile seizures). Other features may include behavioral or emotional problems and intellectual disability. CIPA is caused by mutations in the NTRK1 gene and is inherited in an autosomal recessive manner.^[1] Management is supportive and is aimed at controlling body temperature, preventing self-injury, and treating orthopedic problems.^[2]

Last updated: 1/16/2016

Symptoms Symptoms

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Behavioral abnormality	90%
Cognitive impairment	90%
Impaired pain sensation	90%
Increased bone mineral density	90%
Skin ulcer	90%
Emotional lability	50%
Hyperactivity	50%
Abnormality of dental color	7.5%
Lack of skin elasticity	7.5%
Thickened skin	7.5%
Acral ulceration and osteomyelitis leading to autoamputation of digits	-
Anhidrosis	-
Autosomal recessive inheritance	-
Corneal scarring	-
Corneal ulceration	-
Decreased number of small peripheral myelinated nerve fibers	-
Dysautonomia	-
Episodic fever	-
Hypotrichosis of the scalp	-
Infantile onset	-
Intellectual disability	-
Keratitis	-
Nail dysplasia	-
Nail dystrophy	-
Neuropathic arthropathy	-
Opacification of the corneal stroma	-
Osteomyelitis	-
Pain insensitivity	-
Postural hypotension with compensatory tachycardia	-
Recurrent corneal erosions	-
Self-mutilation	-

Last updated: 10/1/2016

Cause Cause

CIPA is caused by mutations in the NTRK1 gene, which gives the body instructions to make a protein that is important for the development and survival of nerve cells - especially those that carry information about pain, temperature, and touch (sensory neurons). The NTRK1 protein is found on the surface of cells, particularly sensory neurons, and is needed to transmit signals for cell growth and survival. A mutation in the NTRK1 gene can cause it to function abnormally, keeping neurons from receiving proper signaling and causing them to die as a result. This loss of sensory neurons and nerves leading to sweat glands leads to the signs and symptoms of CIPA.^[3]

Last updated: 1/16/2016

Treatment Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

Prognosis Prognosis

The long-term outlook (prognosis) for the hereditary sensory and autonomic neuropathy disorders is improving, and they are no longer considered only as diseases of childhood.^[4] With careful medical attention, people with CIPA can live into adulthood.^[1] The disease may be fatal in the first years of life if hyperpyrexia (exceptionally high fever) is not properly addressed.^[5] Hyperpyrexia is the only persistently related cause of death reported.^[6]

Orthopedic problems are one of the most characteristic and serious complications of CIPA.^[7] In older children, osteomyelitis and bone and/or joint deformities require surgeries, which sometimes involve severe amputations.^[5]

A 2013 article about the epidemiology of CIPA, which included 52 people with CIPA, noted that most were under 40 years of age. However, 4 affected people were over 40. An age distribution chart showed that there was one patient age 40-45, one 50-55, one 55-60, and one 65-70. There were also 2 people whose age was unreported.^[8]

The prognosis for independent functions appears to depend on the degree of severity in each person, and the ability to control the complications of the disease.^[2]

Last updated: 1/16/2016

Do you have updated information on this condition? Let us know.

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Hereditary Neuropathy Foundation Inc.
1751 2nd Avenue, Suite 103
New York, NY 10128
Toll-free: 877-463-1287
Telephone: 212-722-8396
E-mail: info@hnf-cure.org
Website: http://www.hnf-cure.org/
The Center for Peripheral Neuropathy
Department of Neurology
University of Chicago
5841 S. Maryland Ave
MC 2030
Chicago, IL 60637
Website: http://peripheralneuropathycenter.uchicago.edu/
The Foundation for Peripheral Neuropathy
485 Half Day Road
Suite 350
Buffalo Grove, IL 60089
Telephone: +1-877-883-9942
Fax: +1-847-883-9960
E-mail: info@tffpn.org
Website: https://www.foundationforpn.org
The Neuropathy Association
110 W. 40th
Suite #1804
New York, NY 10018
Telephone: 212-692-0662
Fax: 212-692-0668
E-mail: info@neuropathy.org
Website: http://www.neuropathy.org

Organizations Providing General Support

Neuropathy Association
60 East 42nd Street
Suite 942
New York, NY 10165
Telephone: 212-692-0662
E-mail: info@neuropathy.org
Website: http://www.neuropathy.org/

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

Genetics Home Reference (GHR) contains information on Congenital insensitivity to pain with anhidrosis. This website is maintained by the National Library of Medicine.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Congenital insensitivity to pain with anhidrosis. Click on the link to view a sample search on this topic.

Related Diseases Related Diseases

The following diseases are related to Congenital insensitivity to pain with anhidrosis. If you have a question about any of these diseases, you can contact GARD.

Hereditary sensory and autonomic neuropathy

GARD Answers GARD Answers

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Why don't people with CIPA live longer than 25 years old? Why does CIPA effect behavior? What part of the brain makes you feel pain? Is it possible to get it after birth? See answer

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References References

Congenital insensitivity to pain with anhidrosis. Genetics Home Reference. May 2011; http://ghr.nlm.nih.gov/condition/congenital-insensitivity-to-pain-with-anhidrosis.
Hereditary sensory and autonomic neuropathy type 4. Orphanet. November, 2007; http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=642.
NTRK1. Genetics Home Reference. May, 2011; http://ghr.nlm.nih.gov/gene/NTRK1.
Axelrod F & Gold-Von Simson G. Hereditary sensory and autonomic neuropathies: types II, III, and IV. Orphanet Journal of Rare Diseases. 2007; 2:39:http://www.ojrd.com/content/2/1/39.
Rosemberg S, Marie SK, Kliemann S. Congenital insensitivity to pain with anhidrosis (hereditary sensory and autonomic neuropathy type IV). Pediatr Neurol. July, 1994; 11(1):50-56.
Haworth AE, Thomas NH, Cook LJ, Ellison DW & Walker J. Hereditary sensory and autonomic neuropathy with anhidrosis (type IV). J R Soc Med. February, 1998; 91(2):84-86.
Indo Y. Congenital Insensitivity to Pain with Anhidrosis. GeneReviews. April 17, 2014; http://www.ncbi.nlm.nih.gov/books/NBK1769/.
Haga N, Kubota M & Miwa Z. Epidemiology of hereditary sensory and autonomic neuropathy type IV and V in Japan. Am J Med Genet A. April, 2013; 161A(4):871-874.