title: Long QT, syndactyly, joint contractures, stroke and novel CACNA1C mutation: expanding the spectrum of Timothy syndrome.
abstract: 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.
authors: Maritime Medical Genetics Services, IWK Health Centre, Dalhousie University, Halifax, Nova Scotia, Canada.
authors: Jane
authors: J
authors: Gillis
authors: Elena
authors: E
authors: Burashnikov
authors: Charles
authors: C
authors: Antzelevitch
authors: Susan
authors: S
authors: Blaser
authors: Gil
authors: G
authors: Gross
authors: Lesley
authors: L
authors: Turner
authors: Riyana
authors: R
authors: Babul-Hirji
authors: David
authors: D
authors: Chitayat
mesh_terms: D001321:Autistic Disorder; D020746:Calcium Channels, L-Type / Q000235:genetics*; D002874:Chromosome Mapping; D002881:Chromosomes, Human, Pair 12; D003286:Contracture / Q000235:genetics*; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D008133:Long QT Syndrome / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D009154:Mutation; D020156:Salicylic Acid / Q000627:therapeutic use; D020521:Stroke / Q000235:genetics*; D013576:Syndactyly / Q000235:genetics*
chemical_list: C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type; D020156:Salicylic Acid