Long QT, syndactyly, joint contractures, stroke and novel CACNA1C mutation: expanding the spectrum of Timothy syndrome

Am J Med Genet A. 2012 Jan;158A(1):182-7. doi: 10.1002/ajmg.a.34355. Epub 2011 Nov 21.


Timothy syndrome (TS) is an autosomal dominant condition with the constellation of features including prolonged QT interval, hand and foot abnormalities, and mental retardation or autism. Splawski et al. [2004] previously described two phenotypes associated with TS distinguished by two unique and different mutations within the CACNA1C gene. We report on a newborn who presented with prolonged QT interval and associated polymorphic ventricular tachycardia, dysmorphic facial features, syndactyly of the hands and feet, and joint contractures, suggestive of TS. He developed a stroke, subsequent intractable seizures, and was found to have cortical blindness and later profound developmental delay. Initial targeted mutation analysis did not identify either of the previously described TS associated mutations; however, full gene sequencing detected a novel CACNA1C gene mutation (p.Ala1473Gly). The clinical and genetic findings in our case expand both the clinical and molecular knowledge of TS.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autistic Disorder
  • Calcium Channels, L-Type / genetics*
  • Chromosome Mapping
  • Chromosomes, Human, Pair 12
  • Contracture / genetics*
  • Follow-Up Studies
  • Humans
  • Infant, Newborn
  • Long QT Syndrome / genetics*
  • Magnetic Resonance Imaging
  • Mutation*
  • Salicylic Acid / therapeutic use
  • Stroke / genetics*
  • Syndactyly / genetics*


  • CACNA1C protein, human
  • Calcium Channels, L-Type
  • Salicylic Acid

Supplementary concepts

  • Timothy syndrome