A loss-of-function CACNA1A mutation causing benign paroxysmal torticollis of infancy

Eur J Paediatr Neurol. 2014 May;18(3):430-3. doi: 10.1016/j.ejpn.2013.12.011. Epub 2014 Jan 8.

Abstract

Benign paroxysmal torticollis of infancy (BPTI) is a rare paroxysmal disorder characterized by recurrent episodes of head tilt and accompanying general symptoms which remit spontaneously. The rare association with gain-of-function CACNA1A mutations, similar to hemiplegic migraine, has been reported. We report here two new BPTI patients from the same family carrying a heterozygous mutation in the CACNA1A gene leading to the change p.Glu533Lys. Functional analysis revealed that this mutation induces a loss of channel function due to impaired gating by voltage and much lower current density. Our data suggest that BPTI, a periodic syndrome commonly considered a migraine precursor, constitutes an age-specific manifestation of defective neuronal calcium channel activity.

Keywords: Benign paroxysmal torticollis of infancy; CACNA1A; Genetics; P/Q channel; Patch clamp.

Publication types

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

MeSH terms

  • Calcium Channels / genetics*
  • Child, Preschool
  • Humans
  • Male
  • Migraine Disorders / diagnosis
  • Migraine Disorders / etiology
  • Migraine Disorders / genetics
  • Mutation / genetics*
  • Pedigree
  • Torticollis / complications
  • Torticollis / diagnosis
  • Torticollis / genetics*

Substances

  • CACNA1A protein, human
  • Calcium Channels