Long-term follow-up of a patient with type 2 Timothy syndrome and the partial efficacy of mexiletine

Gene. 2021 Apr 20:777:145465. doi: 10.1016/j.gene.2021.145465. Epub 2021 Jan 29.

Abstract

We report a detailed case of type 2 TS due to a p.(Gly402Ser) mutation in exon 8 of the CACNA1C gene. The patient shows a marked prolongation of repolarization with a mean QTc of 540 ms. He shows no structural heart disease, syndactyly, or cranio-facial abnormalities. However, he shows developmental delays, without autism, and dental abnormalities. The cardiac phenotype is very severe, with a resuscitated cardiac arrest at 2.5 years of age, followed by 26 appropriate shocks during nine years of follow-up. Adding mexiletine to nadolol resulted in a reduction of the QTc and a slight decrease in the number of appropriate shocks.

Keywords: Left cardiac sympathetic denervation; Long QT Syndrome; Mexiletine; Timothy syndrome.

Publication types

  • Case Reports

MeSH terms

  • Autistic Disorder / drug therapy*
  • Autistic Disorder / physiopathology*
  • Autistic Disorder / therapy
  • Calcium Channels, L-Type / genetics
  • Child
  • Electrocardiography / methods
  • Exons / genetics
  • Follow-Up Studies
  • Humans
  • Long QT Syndrome / drug therapy*
  • Long QT Syndrome / physiopathology*
  • Long QT Syndrome / therapy
  • Male
  • Mexiletine / metabolism
  • Mexiletine / pharmacology*
  • Mutation / genetics
  • Syndactyly / drug therapy*
  • Syndactyly / genetics
  • Syndactyly / physiopathology*
  • Syndactyly / therapy
  • Treatment Outcome

Substances

  • CACNA1C protein, human
  • Calcium Channels, L-Type
  • Mexiletine

Supplementary concepts

  • Timothy syndrome