Genotype-phenotype correlation in a cohort of paroxysmal kinesigenic dyskinesia cases

J Neurol Sci. 2014 May 15;340(1-2):91-3. doi: 10.1016/j.jns.2014.02.034. Epub 2014 Mar 3.


Background: Recently, PRRT2 gene mutations have been identified as a causative factor of paroxysmal kinesigenic dyskinesia (PKD). However, evidence is still lacking with respect to the genotype to phenotype correlation in PKD patients.

Methods: We recruited a cohort of PKD patients with or without PRRT2 mutations for the study, and followed them for 6 months to observe the response to carbamazepine treatment.

Results: Thirty-four participants were included in this study; 16 patients were positive for a hot-spot p.R217Pfs 8 heterozygous PRRT2 gene mutation, while the other 18 patients were negative for PRRT2 gene mutations. PRRT2 mutations were found to be associated with a younger age of onset, bilateral presence and a higher frequency of attacks. Furthermore, the follow-up study revealed that p.R217Pfs 8-positive patients showed dramatic improvement with complete abolition of dyskinetic episodes with carbamazepine treatment, while only 7 of the 18 patients without PRRT2 mutations showed a response to the antiepileptic drug.

Conclusions: Our study indicated that positivity for PRRT2 mutation is a predictor of younger age of onset and more frequent of attacks in PKD patients. Interestingly, the presence of PRRT2 mutations also predicted a good response to carbamazepine therapy, especially at low dose. Therefore, genetic testing shows potential clinical significance for guiding the choice of medication for individual PKD cases.

Keywords: Carbamazepine; Drug response; Genotype; PRRT2; Paroxysmal kinesigenic dyskinesia; Phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Chorea / genetics*
  • Chorea / physiopathology*
  • Cohort Studies
  • Dystonia
  • Female
  • Genotype*
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Mutation / genetics*
  • Nerve Tissue Proteins / genetics*
  • Phenotype*
  • Young Adult


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

Supplementary concepts

  • Familial paroxysmal dystonia