title: A multicentre study of patients with Timothy syndrome.
abstract: Timothy syndrome (TS) is an extremely rare multisystem disorder characterized by marked QT prolongation, syndactyly, seizures, behavioural abnormalities, immunodeficiency, and hypoglycaemia. The aim of this study was to categorize the phenotypes and examine the outcomes of patients with TS.
  
  
  
  All patients diagnosed with TS in the United Kingdom over a 24-year period were reviewed. Fifteen centres in the British Congenital Arrhythmia Group network were contacted to partake in the study. Six patients with TS were identified over a 24-year period (4 boys and 2 girls). Five out of the six patients were confirmed to have a CACNA1C mutation (p.Gly406Arg) and the other patient was diagnosed clinically. Early presentation with heart block, due to QT prolongation was frequently seen. Four are still alive, two of these have a pacemaker and two have undergone defibrillator implantation. Five out of six patients have had a documented cardiac arrest with three occurring under general anaesthesia. Two patients suffered a cardiac arrest while in hospital and resuscitation was unsuccessful, despite immediate access to a defibrillator. Surviving patients seem to have mild developmental delay and learning difficulties.
  
  
  
  Timothy syndrome is a rare disorder with a high attrition rate if undiagnosed. Perioperative cardiac arrests are common and not always amenable to resuscitation. Longer-term survival is possible, however, patients invariably require pacemaker or defibrillator implantation.
authors.affiliation: Bristol Royal Hospital for Children, University Hospital Bristol, Bristol, UK.|Bristol Heart Institute, University Hospital Bristol, Bristol, UK.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Walsh
authors.affiliation: Department of Congenital Cardiology, Freeman Hospital, Newcastle upon Tyne, UK.|Children's Hospital at Westmead, Sydney, Australia.
authors.forename: Christian
authors.initials: C
authors.lastname: Turner
authors.affiliation: Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
authors.forename: Katherine W
authors.initials: KW
authors.lastname: Timothy
authors.affiliation: Department of Congenital Cardiology, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Neil
authors.initials: N
authors.lastname: Seller
authors.affiliation: Department of Cardiology, The Yorkshire Heart Centre, Leeds General Infirmary, Leeds, UK.
authors.forename: Dominic L
authors.initials: DL
authors.lastname: Hares
authors.affiliation: School of Physiology, Pharmacology and Neuroscience Cardiovascular Research Laboratories, University of Bristol, Bristol, UK.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: James
authors.affiliation: School of Physiology, Pharmacology and Neuroscience Cardiovascular Research Laboratories, University of Bristol, Bristol, UK.
authors.forename: Jules C
authors.initials: JC
authors.lastname: Hancox
authors.affiliation: Department of Cardiology, University Hospital Wales, Cardiff, UK.
authors.forename: Orhan
authors.initials: O
authors.lastname: Uzun
authors.affiliation: Department of Plastic Surgery, University Hospital Wales, Cardiff, UK.
authors.forename: Dean
authors.initials: D
authors.lastname: Boyce
authors.affiliation: Bristol Royal Hospital for Children, University Hospital Bristol, Bristol, UK.|Bristol Heart Institute, University Hospital Bristol, Bristol, UK.
authors.forename: Alan G
authors.initials: AG
authors.lastname: Stuart
authors.affiliation: Department of Clinical Genetics, Freeman Hospital, Newcastle upon Tyne, UK.
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.affiliation: Oxford Medical Genetics Laboratories, Cardiac Service, Oxford University Hospitals NHS Trust, The Churchill Hospital, Oxford, UK.
authors.forename: Caroline
authors.initials: C
authors.lastname: Sarton
authors.affiliation: Oxford Medical Genetics Laboratories, Cardiac Service, Oxford University Hospitals NHS Trust, The Churchill Hospital, Oxford, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: McGuire
authors.affiliation: Department of Clinical Genetics, University Hospital Bristol, Bristol, UK.
authors.forename: Ruth A
authors.initials: RA
authors.lastname: Newbury-Ecob
authors.affiliation: Department of Cardiology, Royal Hospital for Sick Children, Glasgow, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Mcleod
mesh_terms: D001321:Autistic Disorder / Q000150:complications / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D020746:Calcium Channels, L-Type / Q000235:genetics; D002304:Cardiac Pacing, Artificial; D017147:Defibrillators, Implantable; D004554:Electric Countershock / Q000295:instrumentation; D004562:Electrocardiography; D005260:Female; D020022:Genetic Predisposition to Disease; D006323:Heart Arrest / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D006327:Heart Block / Q000209:etiology / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008133:Long QT Syndrome / Q000150:complications / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D008297:Male; D009154:Mutation; D010138:Pacemaker, Artificial; D010641:Phenotype; D011379:Prognosis; D012151:Resuscitation; D013576:Syndactyly / Q000150:complications / Q000235:genetics / Q000503:physiopathology / Q000628:therapy; D013997:Time Factors; D006113:United Kingdom
chemical_list: C079146:CACNA1C protein, human; D020746:Calcium Channels, L-Type
keywords: Cardiac arrest; Defibrillator; Long QT; Paediatrics; Timothy syndrome