Congenital insensitivity to pain with anhidrosis

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disorder of the nervous system which prevents the feeling of pain or temperature, and prevents a person from sweating. Cognitive disorders are commonly coincident. CIPA is the fourth type of hereditary sensory and autonomic neuropathy (HSAN), and is also known as HSAN IV.

Charcot joints are shown in this boy with CIPA. His right knee and right ankle 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.
Congenital insensitivity to pain with anhidrosis
Other nameshereditary sensory and autonomic neuropathy type IV
SpecialtyNeurology

Signs and symptoms

Signs of CIPA are present from infancy. Infants may present with seizures related to hyperthermia. Because people with this condition are unable to sweat, they are unable to regulate their body temperature.[1] Those affected are unable to feel pain and temperature, but retain the ability to feel touch.

Lack of pain puts those with CIPA at a high risk for accidental self-mutilation. Corneal ulceration occurs due to lack of protective impulses.[2] Joint and bone problems are common due to repeated injuries, and wounds heal poorly.[3]

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 is caused by a mutation in NTRK1, a gene encoding the neurotrophic tyrosine kinase receptor.[4] 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.[5]

Mitochondrial abnormalities in muscle cells have been found in people with CIPA. Skin biopsies show a lack of innervation of the eccrine glands[2] and nerve biopsies show a lack of small myelinated and unmyelinated fibers.[2][6]

Diagnosis

Diagnosis is made based on clinical criteria and can be confirmed with genetic testing.[1]

Treatment

There is no treatment for CIPA. Attention to injuries to prevent infection and worsening is necessary.[1]

Epidemiology

The condition is inherited and is most common among Israeli Bedouins.[2]

Approximately 20% of people with CIPA die of hyperthermia by age 3.[2]

References
  1. Fenichel's Clinical Pediatric Neurology (6 ed.). Elsevier. 2013. pp. 207–214.
  2. Tachdjian's Pediatric Orthopaedics (5 ed.). Saunders Elsevier. 2014. pp. 285–319.
  3. Swaiman's Pediatric Neurology (6 ed.). Elsevier. 2017. pp. e2652–e2669.
  4. 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.
  5. Indo, Yasuhiro. "Mutations in the TRKA/NGF Receptor Gene in Patients with Congenital Insensitivity to Pain with Anhidrosis" (PDF). Kumamoto University. Retrieved 7 December 2011.
  6. Volpe's Neurology of the Newborn (6 ed.). Elsevier. 2018. pp. 887–921.

Further reading
  • Indo, Y; Pagon, RA; Adam, MP; Ardinger, HH; Wallace, SE; Amemiya, A; Bean, LJH; Bird, TD; Ledbetter, N; Mefford, HC; Smith, RJH; Stephens, K (1993). "Congenital Insensitivity to Pain with Anhidrosis". University of Washington, Seattle. PMID 20301726. Retrieved 8 July 2017. Cite journal requires |journal= (help)
Classification
External resources
This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.