Mutations in PRRT2 result in familial infantile seizures with heterogeneous phenotypes including febrile convulsions and probable SUDEP

Epilepsy Res. 2013 May;104(3):280-4. doi: 10.1016/j.eplepsyres.2012.10.014. Epub 2013 Jan 23.

Abstract

Mutations of PRRT2, which encodes proline-rich transmembrane protein 2, are associated with heterogeneous phenotypes including benign familial infantile seizures (BFIS) and/or familial paroxysmal kinesigenic dystonia (PKD). Here, we performed mutation screening of PRRT2 in six Italian families with BFIS/PKD phenotypes. The mutation, c.649dupC (p.Arg217ProfsX8), was found in two families with BFIS phenotype. In a third BFIS family, a missense mutation, c.718C/T (R240X), was identified. All these mutations co-segregated with the disease and were not observed in 100 controls of matched ancestry. In one BFIS family that carried the c.649dupC mutation, one affected member developed afebrile focal seizures and died at age of 14 years of probable sudden unexpected death in epilepsy, while his brother also had simple febrile convulsions (FC) and performed poorly on complex psychomotor functioning. In another family carrying the c.718C/T mutation, two of three affected members also had simple FC. This study enlarges the clinical spectrum related to PPRT2 mutations and underscores the complexity of the phenotypic consequences of mutations in this gene.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Dystonia / diagnosis
  • Dystonia / genetics*
  • Epilepsy, Benign Neonatal / complications
  • Epilepsy, Benign Neonatal / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Infant
  • Male
  • Membrane Proteins / genetics*
  • Mutation / genetics*
  • Nerve Tissue Proteins / genetics*
  • Pedigree
  • Phenotype
  • Seizures / diagnosis
  • Seizures / etiology
  • Seizures / genetics*
  • Seizures, Febrile / diagnosis
  • Seizures, Febrile / etiology
  • Seizures, Febrile / genetics*

Substances

  • Membrane Proteins
  • Nerve Tissue Proteins
  • PRRT2 protein, human

Supplementary concepts

  • Familial paroxysmal dystonia