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Disease Profile

Congenital insensitivity to pain with anhidrosis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Infancy

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ICD-10

G60.8

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Neuropathy, congenital sensory, with anhidrosis; CIPA; Hereditary sensory and autonomic neuropathy 4;

Categories

Congenital and Genetic Diseases; Nervous System Diseases

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]

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.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormality of peripheral nerve conduction
0003134
Anhidrosis
Lack of sweating
Sweating dysfunction

[ more ]

0000970
Aplasia of the sweat glands
Absent sweat glands
Lack of sweat glands

[ more ]

0011136
Impaired temperature sensation
Abnormality of temperature sensation
Loss of temperature sensation

[ more ]

0010829
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249
Osteomyelitis
Bone infection
0002754
Pain insensitivity
0007021
Recurrent Staphylococcus aureus infections
0002726
Self-mutilation
Deliberate self-harm
Self mutilation

[ more ]

0000742
30%-79% of people have these symptoms
Abnormality of humoral immunity
0005368
Atypical scarring of skin
Atypical scarring
0000987
Difficulty walking
Difficulty in walking
0002355
Dry skin
0000958
Emotional lability
Emotional instability
0000712
Fasciitis
Inflammation of the fascia
0100537
Hyperactivity
More active than typical
0000752
Lichenification
0100725
Nail-biting
0012170
Neuropathic arthropathy
0002821
Painless fractures due to injury
0002661
Premature loss of teeth
Early tooth loss
Loss of teeth
Premature teeth loss
Premature tooth loss

[ more ]

0006480
Recurrent fever
Episodic fever
Increased body temperature, episodic
Intermittent fever

[ more ]

0001954
Specific learning disability
0001328
Trophic limb changes
0003091
5%-29% of people have these symptoms
Abnormal lumbar spine morphology
0100712
Abnormality of the ankles
0003028
Abnormality of the hip bone
Abnormality of the hips
0003272
Alveolar ridge overgrowth
Overgrowth of gum ridge
0009085
Anemia
Low number of red blood cells or hemoglobin
0001903
Avascular necrosis
Death of bone due to decreased blood supply
0010885
Bruising susceptibility
Bruise easily
Easy bruisability
Easy bruising

[ more ]

0000978
Decreased corneal reflex
0008000
Distal sensory impairment
Decreased sensation in extremities
0002936
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Growth delay
Delayed growth
Growth deficiency
Growth failure
Growth retardation
Poor growth
Retarded growth

[ more ]

0001510
Impulsivity
Impulsive
0100710
Orthostatic hypotension due to autonomic dysfunction
0004926
Recurrent aspiration pneumonia
0002100
Septic arthritis
0003095
Short attention span
Poor attention span
Problem paying attention

[ more ]

0000736
Syncope
Fainting spell
0001279
Tongue pain
0030811
Tooth abscess
0030757
Unexplained fevers
0001955
1%-4% of people have these symptoms
Chronic kidney disease
0012622
Corneal scarring
0000559
Corneal ulceration
0012804
Hyperesthesia
0100963
Hyperhidrosis
Excessive sweating
Increased sweating
Profuse sweating
Sweating
Sweating profusely
Sweating, increased

[ more ]

0000975
Hypothermia
Abnormally low body temperature
0002045
Percent of people who have these symptoms is not available through HPO
Acral ulceration
0006121
Autoamputation of digits
0007460
Autosomal recessive inheritance
0000007
Decreased number of small peripheral myelinated nerve fibers
0007249
Global developmental delay
0001263
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
Keratitis
Corneal inflammation
0000491
Nail dysplasia
Atypical nail growth
0002164
Nail dystrophy
Poor nail formation
0008404
Opacification of the corneal stroma
0007759
Poor wound healing

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]

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

    Organizations Providing General Support

      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.

          References

          1. 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:
          2. Congenital insensitivity to pain with anhidrosis. Genetics Home Reference. May 2011; https://ghr.nlm.nih.gov/condition/congenital-insensitivity-to-pain-with-anhidrosis.
          3. Hereditary sensory and autonomic neuropathy type 4. Orphanet. November, 2007; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=642.
          4. NTRK1. Genetics Home Reference. May, 2011; https://ghr.nlm.nih.gov/gene/NTRK1.
          5. 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.
          6. Axelrod F & Gold-Von Simson G. Hereditary sensory and autonomic neuropathies: types II, III, and IV. Orphanet Journal of Rare Diseases. 2007; 2:39:https://www.ojrd.com/content/2/1/39.
          7. 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.
          8. 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.
          9. 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.
          10. Indo Y. Congenital Insensitivity to Pain with Anhidrosis. GeneReviews. April 17, 2014; https://www.ncbi.nlm.nih.gov/books/NBK1769/.

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