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

This disease is grouped under:

Hereditary sensory and autonomic neuropathy

Summary Summary

Congenital insensitivity to pain with anhidrosis (CIPA) also known as hereditary sensory and autonomic neuropathy type IV, is an inherited disease where there is an 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 dental caries, difficulty controlling urine and defecating (urine and fecal incontinence), behavioral or emotional problems and intellectual disability.^[1]^[2] CIPA is caused by changes (mutations) in the NTRK1 gene. Inheritance is autosomal recessive.^[2] There is still no cure for CIPA. Treatment is aimed at controlling body temperature, preventing self-injury, and treating orthopedic problems, as soon as possible. It is very important to control the body temperature during surgery.^[1]^[3]

Last updated: 12/8/2017

Symptoms Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Global developmental delay		0001263
Impaired pain sensation	Decreased pain sensation	0007328
Intellectual disability	Mental deficiency Mental retardation Mental retardation, nonspecific Mental-retardation [ more ]	0001249
Irritability	Irritable	0000737
Osteomyelitis	Bone infection	0002754
Self-injurious behavior	Self-injurious behaviour	0100716
Skin ulcer	Open skin sore	0200042
30%-79% of people have these symptoms
Emotional lability	Emotional instability	0000712
Hyperactivity	More active than typical	0000752
5%-29% of people have these symptoms
Abnormality of dental color	Abnormality of tooth color Abnormality of tooth shade [ more ]	0011073
Lack of skin elasticity		0100679
Thickened skin	Thick skin	0001072
Percent of people who have these symptoms is not available through HPO
Acral ulceration		0006121
Anhidrosis	Lack of sweating Sweating dysfunction [ more ]	0000970
Autoamputation of digits		0007460
Autosomal recessive inheritance		0000007
Corneal scarring		0000559
Corneal ulceration		0012804
Decreased number of small peripheral myelinated nerve fibers		0007249
Hypotrichosis of the scalp	Reduced/lack of hair on scalp	0004782
Infantile onset	Onset in first year of life Onset in infancy [ more ]	0003593
Keratitis	Corneal inflammation	0000491
Lichenification		0100725
Nail dysplasia	Atypical nail growth	0002164
Nail dystrophy	Poor nail formation	0008404
Neuropathic arthropathy		0002821
Opacification of the corneal stroma		0007759
Pain insensitivity		0007021
Poor wound healing		0001058
Postural hypotension with compensatory tachycardia		0005307
Recurrent corneal erosions	Recurrent breakdown of clear protective layer of eye	0000495
Recurrent fever	Episodic fever Increased body temperature, episodic Intermittent fever [ more ]	0001954
Self-mutilation	Deliberate self-harm Self mutilation [ more ]	0000742

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 7/1/2019

Do you have updated information on this disease? We want to hear from you.

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.^[4]

Studies of brain belonging to people with CIPA have shown abnormalities in the parts of the brain responsible for pain and temperature sensations such as absence of small neurons and fibers in the dorsal ganglia and dorsal roots that contains the cell bodies of sensory neurons that bring information from the periphery to the spinal cord, absence of Lissauer’s tract, made up of fibers convey primarily pain, temperature and light touch information, and reduction in size of the spinal tract of the trigeminal nerve that receives information about deep/crude touch, pain, and temperature from the same side of the face.^[5]

Last updated: 12/8/2017

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.^[6] The prognosis appears to depend on the degree of severity in each person, and the ability to control the complications of the disease.^[3] However, with careful medical attention, people with CIPA can live into adulthood.^[2]^[7]

The main problems are related to the high temperature and the bone problems that are present in CIPA. The disease may be fatal in the first years of life if hyperpyrexia (very high fever) is not properly managed, and it is the most frequently reported cause of death.^[8]^[9]

Orthopedic problems are also one of the most characteristic and serious complications of CIPA.^[10] In older children, osteomyelitis and bone and/or joint deformities require surgeries, which sometimes may need amputations.^[9]

Last updated: 12/8/2017

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare 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 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.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis includes other HSAN disorders. What distinguishes HSAN4 is the extensive involvement of ectodermal structures including skin, bone and nervous system, and especially absent or markedly decreased sweating. Visit the Orphanet disease page for more information.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s 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.
401 Park Avenue, 10th Floor
New York, NY 10016
Toll-free: 1-855-435-7268
Telephone: +1-212-722-8396
Fax: +1-917-591-2758
E-mail: info@hnf-cure.org
Website: https://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: https://www.foundationforpn.org/contact-us/
Website: https://www.foundationforpn.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? We want to hear from you.

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

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.
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.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

References References

Pérez-López LM, Cabrera-González M, Gutiérrez-de la Iglesia D, Ricart S & Knörr-Gim G. Update Review and Clinical Presentation in Congenital Insensitivity to Pain and Anhidrosis. Case Reports in Pediatrics. 2015; 2015:
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.
Iijima M & Haga N. Evaluation of nonnociceptive sensation in patients with congenital insensitivity to pain with anhidrosis. Childs Nerv Syst. August, 2010; 26(8):1742-6. https://www.ncbi.nlm.nih.gov/pubmed/20013280.
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.
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.
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.
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.
Indo Y. Congenital Insensitivity to Pain with Anhidrosis. GeneReviews. April 17, 2014; http://www.ncbi.nlm.nih.gov/books/NBK1769/.