| Congenital insensitivity to pain with anhidrosis |
| Classification and external resources |
| OMIM |
256800 |
| DiseasesDB |
32097 |
| MeSH |
D009477 |
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" means that the condition is present from birth.
Contents
- 1 Clinical description
- 2 Differential diagnosis
- 3 Cause
- 4 In the media
- 5 See also
- 6 References
- 7 External links
Clinical description
Charcot joints are demonstrated in this boy with HSAN IV or congenital insensitivity to pain with anhidrosis (CIPA). The right knee and right ankle (on the left of the picture) 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.
Patients with this disorder are very likely to injure themselves in ways that would normally be prevented by feeling pain. 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]
Differential diagnosis
Congenital insensitivity to pain with anhidrosis may be misdiagnosed for leprosy, based on similar symptoms of severe injuries to the hands and feet.
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 (NTRK1 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]
In the media
The manga and anime series Loveless features 4 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.
In the seventh season of the TV series Criminal Minds in the episode "Painless" (4th episode), the unknown subject of the episode suffers from the condition.
Baby Carson was featured on Discovery Health Channel's Mystery Diagnosis episode "The Boy Who Never Cried", which aired on 21 November 2009. Dr. David Christopher of Valley Children's Clinic, Renton, Washington is his doctor.
In Stieg Larsson's novel The Girl Who Played with Fire, one of the villains, known through most of the book as the "blonde giant", suffers from the disorder.
In the 2010 film Bereavement, 6 year old Martin Bristol, one of the main characters, suffers from CIPA.
In the BBC1 hospital drama Holby City, in the episode entitled "Wolf's Clothing", first broadcast on 15 May 2012, a teenage girl called Kitty is found to have CIPA, which is responsible for her heart condition having been undiagnosed.
In the Show TV drama Sleepers, one of the main characters, Gazanfer Bircan, had CIPA when he was a child. Symptoms of the disease continue when he is 30 years old. Because of CIPA, he harms and injures people around him.
In the book The Rook by Steven James, the character Creighton Malice suffers from this condition.
In the Japanese BL game DRAMAtical Murder one of the main characters, Noiz, is unable to feel pain.
In the first season of the TV series The Blacklist in the fifth episode "The Courier (No. 85)", The Courier utilizes the condition to hide objects, such as the chip the FBI needs, underneath his skin. Within this episode, it is simply referred to as Congenital Anhidrosis, not by its full name.
The light novel and anime series Kara no Kyoukai, in Remaining Sense of Pain, features Asagami Fujino, a girl whose magic-supressing medication had the side effect of destroying her ability to feel pain.
See also
- Hereditary sensory and autonomic neuropathy
- Congenital insensitivity to pain
- Nociception
References
- ^ Abdel-Hafez, Hisham; Sarah Mohamed Awad (June 2007). "Congenital Insensitivity to Pain with Anhidrosis (CIPA)". Egyptian Dermatology Online Journal 3 (1). Retrieved 7 December 2011.
- ^ Mardy, Sek; Yuichi Miura, Fumio Endo, Ichiro Matsuda, Yasuhiro Indo (2001). "Congenital Insensitivity to pain with anhidrosis (CIPA): effect of TRKA (NTRK1) missense mutations on autophosphorylation of the receptor tyrosine kinase for nerve growth factor". Human Molecular Genetics 10 (3): 179–188. Retrieved 7 December 2011.
- ^ Shatzky S, Moses S, Levy J, et al. (June 2000). "Congenital insensitivity to pain with anhidrosis (CIPA) in Israeli-Bedouins: genetic heterogeneity, novel mutations in the TRKA/NGF receptor gene, clinical findings, and results of nerve conduction studies". Am. J. Med. Genet. 92 (5): 353–60. doi:10.1002/1096-8628(20000619)92:5<353::AID-AJMG12>3.0.CO;2-C. PMID 10861667.
- ^ Indo, Yasuhiro. "Mutations in the TRKA/NGF Receptor Gene in Patients with Congenital Insensitivity to Pain with Anhidrosis". Kumamoto University. Retrieved 7 December 2011.
External links
- The Facts of Painless People The website of two adults on separate sides of the world who were born with CIPA.
- Help Roberto The website of young boy with CIPA. Features Roberto's specific case, information about CIPA, and links to videos on CNN and the Discovery Channel. (Site has ended, link from Archive.org)
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Autonomic diseases, Dysautonomia, autonomic- neuropathy (G90, 337)
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| HSAN |
- I
- II
- III/Familial dysautonomia
- IV/Congenital insensitivity to pain with anhidrosis
- V
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| Orthostatic intolerance |
- Postural orthostatic tachycardia syndrome
- Orthostatic hypotension
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| Other |
- Horner's syndrome
- Multiple system atrophy
- Pure autonomic failure
- Autonomic dysreflexia
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|
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anat (h/r/t/c/b/l/s/a)/phys (r)/devp/prot/nttr/nttm/ntrp
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noco/auto/cong/tumr, sysi/epon, injr
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|
|
|
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Genetic disorder, membrane: cell surface receptor deficiencies
|
|
G protein-coupled receptor
(including hormone) |
| Class A |
- TSHR (Congenital hypothyroidism 1)
- LHCGR (Male-limited precocious puberty)
- FSHR (XX gonadal dysgenesis)
- EDNRB (ABCD syndrome, Waardenburg syndrome 4a, Hirschsprung's disease 2)
- AVPR2 (Nephrogenic diabetes insipidus 1)
- PTGER2 (Aspirin-induced asthma)
|
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| Class B |
- PTH1R (Jansen's metaphyseal chondrodysplasia)
|
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| Class C |
- CASR (Familial hypocalciuric hypercalcemia)
|
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| Class F |
- FZD4 (Familial exudative vitreoretinopathy 1)
|
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Enzyme-linked receptor
(including
growth factor) |
| RTK |
- ROR2 (Robinow syndrome)
- FGFR1 (Pfeiffer syndrome, KAL2 Kallmann syndrome)
- FGFR2 (Apert syndrome, Antley–Bixler syndrome, Pfeiffer syndrome, Crouzon syndrome, Jackson–Weiss syndrome)
- FGFR3 (Achondroplasia, Hypochondroplasia, Thanatophoric dysplasia, Muenke syndrome)
- INSR (Donohue syndrome
- Rabson–Mendenhall syndrome)
- NTRK1 (Congenital insensitivity to pain with anhidrosis)
- KIT (KIT Piebaldism, Gastrointestinal stromal tumor)
|
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| STPK |
- AMHR2 (Persistent Mullerian duct syndrome II)
- TGF beta receptors: Endoglin/Alk-1/SMAD4 (Hereditary hemorrhagic telangiectasia)
- TGFBR1/TGFBR2 (Loeys-Dietz syndrome)
|
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| GC |
- GUCY2D (Leber's congenital amaurosis 1)
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| JAK-STAT |
- Type I cytokine receptor: GH (Laron syndrome)
- CSF2RA (Surfactant metabolism dysfunction 4)
- MPL (Congenital amegakaryocytic thrombocytopenia)
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| TNF receptor |
- TNFRSF1A (TNF receptor associated periodic syndrome)
- TNFRSF13B (Selective immunoglobulin A deficiency 2)
- TNFRSF5 (Hyper-IgM syndrome type 3)
- TNFRSF13C (CVID4)
- TNFRSF13B (CVID2)
- TNFRSF6 (Autoimmune lymphoproliferative syndrome 1A)
|
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| Lipid receptor |
- LRP: LRP2 (Donnai–Barrow syndrome)
- LRP4 (Cenani–Lenz syndactylism)
- LRP5 (Worth syndrome, Familial exudative vitreoretinopathy 4, Osteopetrosis 1)
- LDLR (LDLR Familial hypercholesterolemia)
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| Other/ungrouped |
- Immunoglobulin superfamily: AGM3, 6
- Integrin: LAD1
- Glanzmann's thrombasthenia
- Junctional epidermolysis bullosa with pyloric atresia
EDAR (EDAR Hypohidrotic ectodermal dysplasia)
- PTCH1 (Nevoid basal cell carcinoma syndrome)
- BMPR1A (BMPR1A Juvenile polyposis syndrome)
- IL2RG (X-linked severe combined immunodeficiency)
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- See also
- cell surface receptors
- B structural
- perx
- skel
- cili
- mito
- nucl
- sclr
- DNA/RNA/protein synthesis
- membrane
- transduction
- trfk
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Pain and nociception
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| By region/system |
| HEENT |
- Headache
- Neck
- Odynophagia (swallowing)
- Otalgia (ear)
- Toothache
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| Chest pain |
| Cardiovascular system |
|
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| Respiratory system |
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| Breast |
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| Musculoskeletal |
- Arthralgia (joint)
- Bone pain
- Myalgia (muscle)
- Muscle soreness: Acute / Delayed onset
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| Neurologic |
- Congenital insensitivity to pain
- HSAN
- Type I
- II congenital sensory neuropathy
- III familial dysautonomia
- IV congenital insensitivity to pain with anhidrosis
- V congenital insensitivity to pain with partial anhidrosis
- Neuralgia
- Pain asymbolia
- Pain disorder
- Paroxysmal extreme pain disorder
- Allodynia
- Chronic pain
- Hyperalgesia
- Hypoalgesia
- Hyperpathia
- Phantom pain
- Referred pain
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| Abdominal pain |
| Urogenital |
- Dysuria
- Pelvic pain
- Dyspareunia
- Testicular pain
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| Gastrointestinal |
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| Back |
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| Tests |
- Cold pressor test
- Dolorimeter
- Hot plate test
- Tail flick test
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| Related concepts |
- Anterolateral system
- Pain management
- Pain scale
- Pain threshold
- Pain tolerance
- Posteromarginal nucleus
- Substance P
- Suffering
- OPQRST
- Philosophy of pain
- Cancer pain
- Drug-seeking behavior
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anat (n/s/m/p/4/e/b/d/c/a/f/l/g)/phys/devp
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noco (m/d/e/h/v/s)/cong/tumr, sysi/epon, injr
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proc, drug (N1A/2AB/C/3/4/7A/B/C/D)
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anat (h/r/t/c/b/l/s/a)/phys (r)/devp/prot/nttr/nttm/ntrp
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noco/auto/cong/tumr, sysi/epon, injr
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