Disease Information for Pain, indifference, congenital

INDIFFERENCE TO PAIN, CONGENITAL, AUTOSOMAL RECESSIVE;

INSENSITIVITY TO PAIN, CHANNELOPATHY-ASSOCIATED;

CONGENITAL ANALGESIA, AUTOSOMAL RECESSIVE; ASYMBOLIA FOR PAIN; Gene map locus 2q24; autosomal recessive congenital indifference to pain can be caused by loss-of-function mutations in the SCN9A gene Autosomal dominant primary erythermalgia is caused by gain-of-function mutations in the same gene; there is a possible autosomal dominant form of congenital indifference to pain;

Many cases reported as congenital indifference to pain or congenital analgesia were reported before the development of methods to assess the physiologic function of nerve fibers; Cox suggested that congenital indifference to pain due to mutations in the SCN9A gene is actually a form of insensitivity to pain since the defect is due to a channelopathy that is not normally detected by routine histopathology; The authors proposed the term "channelopathy-associated insensitivity to pain" for the disorder described here; Individuals with congenital indifference to pain have painless injuries beginning in infancy but otherwise normal sensory modalities; Perception of passive movement, joint position, and vibration are normal, as are tactile thresholds and light touch perception; Reflexes and autonomic responses are also normal; The axonal flare response after intradermal injection of histamine is normal, a finding that is in contrast to HSAN; Cases from consanguineous parents, and parental consanguinity has been noted in other cases suggesting autosomal recessive inheritance;

Gilly et al (1964) described 2 affected sibs who were born of normal parents and were of normal intelligence; Osuntokun et al (1968) described brother and half sister with congenital indifference to pain, who presumably had different fathers, both normal; They referred to the condition as "pain asymbolia" and noted the association of auditory imperception; Cox et al (2006) described individuals from 3 Pakistani families with congenital inability to perceive any form of pain, in whom all other sensory modalities were preserved and the peripheral and central nervous systems were apparently otherwise intact; The trait was segregating as an autosomal recessive in the family; All affected individuals had injuries to their lips (some requiring plastic surgery) and/or tongue (with loss the distal third in 2 cases), caused by biting themselves in the first 4 years of life; The children were considered of normal intelligence by their parents and teachers; All could correctly perceive sensations of touch, warm and cold temperature, propioception, tickle and pressure, but not painful stimuli; MAPPING: In 3 northern Pakistani families segregating autosomal recessive "channelopathy-associated insensitivity to pain," Cox et al (2006) mapped the trait to 2q24_3, a region containing the SCN9A gene, which encodes the alpha subunit of the voltage-gated sodium channel, Nav1_7

MOLECULAR GENETICS: By sequence analysis of the SCN9A gene in 3 northern Pakistani families segregating autosomal recessive "channelopathy-associated insensitivity to pain,"

(Edit)