Clinical and genetic aspects of congenital insensitivity to pain with anhidrosis

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive genetic disease, which is characterized by recurrent episodes of fever, anhidrosis, self mutilation, absence of reaction to noxious stimuli, prolonged healing times and mental retardation. The absence of pain sensation combined with mental retardation predisposes the children to recurrent wound infections and deep ulcers that heal at a slower pace than seen in healthy people. The anomalous pain is due to the absence of dorsal root ganglia that are responsible for pain sensation and absence of afferent neurons activated by tissue damaging stimuli. Nerve Growth Factor (NGF) is a growth factor that supports the survival of nociceptive sensory and autonomic sympathetic neurons. Neurotrophin Tyrosine Receptor (NTRK1) encodes a receptor tyrosine kinase that is activated in response to NGF. NTRK1 mutations have been found in mice that presented with clinical signs similar to CIPA, subsequently CIPA patients have been examined for these mutations as well. Currently, 37 different mutations at the NTRK1 are known which cause CIPA. The above syndrome is so rare that until the year 2000 only 84 cases have been reported, not including 28 known cases of CIPA patients from Israeli Bedouins. Since no cure is available, prenatal screening, as conducted in our institution, is the only available preventive option to avoid the birth of an affected child.