title: Heterogeneous Phenotype of Long QT Syndrome Caused by the KCNH2-H562R Mutation: Importance of Familial Genetic Testing.
abstract: OBJECTIVE
  Long QT syndrome is an inherited ion channelopathy that leads to syncope and sudden death. Because of the heterogeneous phenotype of this disease, genetic testing is fundamental to detect individuals with concealed long QT syndrome. In this study, we determined the features of a family with 13 carriers of the KCNH2-H562R missense mutation, which affects the pore region of the HERG channel.
  
  
  METHODS
  We identified the KCNH2-H562R mutation in a 65-year-old man with a prolonged QTc interval who had experienced an episode of torsade de pointes. Subsequently, a total of 13 mutation carriers were identified in the family. Carriers (age 48 [26] years; 46% males) underwent clinical evaluation, electrocardiography and echocardiography.
  
  
  RESULTS
  The mean (standard deviation) QTc in carriers was 493 (42) ms (3 [23%] showed normal QTc); 6 (46%) had symptoms (4, syncope; 1, sudden death; 1, aborted sudden death [proband]). While under treatment with beta-blockers, 11 of 12 carriers (92%) remained asymptomatic at 5 years of follow-up (1 patient required left cardiac sympathectomy). The QTc shortening with beta-blockers was 50 (37) ms. There was 1 sudden death in a patient who refused treatment.
  
  
  CONCLUSIONS
  Family study is essential in the interpretation of a genetic testing result. This article describes the heterogeneous and variable phenotype of a large family with the KCNH2-H562R mutation and highlights the role of genetic study for the appropriate identification of at-risk individuals who would benefit from treatment.
authors.affiliation: Servicio de Cardiología, Hospital Clínico Universitario Virgen de la Arrixaca, Universidad de Murcia, IMIB-Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Carmen
authors.initials: C
authors.lastname: Muñoz-Esparza
authors.affiliation: Servicio de Análisis Clínicos, Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Esperanza
authors.initials: E
authors.lastname: García-Molina
authors.affiliation: Servicio de Cardiología, Hospital Clínico Universitario Virgen de la Arrixaca, Universidad de Murcia, IMIB-Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Mariela
authors.initials: M
authors.lastname: Salar-Alcaraz
authors.affiliation: Servicio de Cardiología, Hospital Clínico Universitario Virgen de la Arrixaca, Universidad de Murcia, IMIB-Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Peñafiel-Verdú
authors.affiliation: Servicio de Cardiología, Hospital Clínico Universitario Virgen de la Arrixaca, Universidad de Murcia, IMIB-Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Sánchez-Muñoz
authors.affiliation: Servicio de Cardiología, Hospital Clínico Universitario Virgen de la Arrixaca, Universidad de Murcia, IMIB-Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Martínez Sánchez
authors.affiliation: Servicio de Hematología, Hospital Clínico Universitario Virgen de la Arrixaca, Universidad de Murcia, IMIB-Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Valentín
authors.initials: V
authors.lastname: Cabañas-Perianes
authors.affiliation: Servicio de Cardiología, Hospital Clínico Universitario Virgen de la Arrixaca, Universidad de Murcia, IMIB-Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Mariano
authors.initials: M
authors.lastname: Valdés Chávarri
authors.affiliation: Servicio de Cardiología, Hospital Clínico Universitario Virgen de la Arrixaca, Universidad de Murcia, IMIB-Arrixaca, El Palmar, Murcia, Spain.
authors.forename: Arcadio
authors.initials: A
authors.lastname: García Alberola
authors.affiliation: Servicio de Cardiología, Hospital Clínico Universitario Virgen de la Arrixaca, Universidad de Murcia, IMIB-Arrixaca, El Palmar, Murcia, Spain. Electronic address: jgimeno@secardiologia.es.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Gimeno-Blanes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D000072237:ERG1 Potassium Channel / Q000235:genetics* / Q000378:metabolism; D004562:Electrocardiography; D005260:Female; D005820:Genetic Testing; D006329:Heart Conduction System / Q000503:physiopathology*; D006579:Heterozygote; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D055815:Young Adult
chemical_list: D000072237:ERG1 Potassium Channel; C000606913:KCNH2 protein, human; D004247:DNA
keywords: Gen KCNH2; KCNH2 gene; Long QT syndrome; Muerte súbita; Sudden death; Síndrome de QT largo