Paroxysmal extreme pain disorder: a molecular lesion of peripheral neurons

Nat Rev Neurol. 2011 Jan;7(1):51-5. doi: 10.1038/nrneurol.2010.162. Epub 2010 Nov 16.

Abstract

Background: a 3-month-old male infant presented, beginning on the second day of life, with paroxysmal painful events that started with tonic contraction of the whole body followed by erythematous harlequin-type color changes.

Investigations: screening of the SCN9A gene, which encodes the voltage-gated sodium channel Na(V)1.7, identified a new mutation, Gly1607Arg, located within the domain IV S4 voltage sensor. Whole-cell patch-clamp analysis demonstrated functional effects of the mutant channel that included impaired inactivation-a hallmark of paroxysmal extreme pain disorder (PEPD).

Diagnosis: the patient was diagnosed as having PEPD, an autosomal dominant disorder characterized by severe rectal pain triggered by defecation or perineal stimulation, usually followed by ocular or submaxillary pain. Erythematous flushing, sometimes in a harlequin pattern, can be a prominent feature of this condition.

Management: treatment with carbamazepine (10 mg/kg/day) for approximately 3 months was ineffective in this case, and the parents made a decision to discontinue the drug. The mother was instructed to avoid painful stimuli that could trigger an episode.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Chromosome Disorders
  • Humans
  • Infant
  • Male
  • Mutation
  • NAV1.7 Voltage-Gated Sodium Channel
  • Neuralgia / genetics*
  • Neuralgia / physiopathology
  • Sodium Channels / genetics*

Substances

  • NAV1.7 Voltage-Gated Sodium Channel
  • SCN9A protein, human
  • Sodium Channels