Appropriate time interval to update ambiguous genetic diagnosis in inherited arrhythmogenic syndromes
Estefanía Martínez-Barrios,
Andrea Greco,
Sergi Cesar,
Carles Díez-López,
José Cruzalegui,
Nuria Díez-Escuté,
Patricia Cerralbo,
Fredy Chipa,
Irene Zschaeck,
Simone Grassi,
Antonio Oliva,
Norma Balderrábano,
Rocío Toro,
Georgia Sarquella-Brugada,
Oscar Campuzano
Affiliations
Estefanía Martínez-Barrios
Pediatric Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain; Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Cardiovascular Diseases in the Development, Institut de Recerca Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, the Netherlands
Andrea Greco
Pediatric Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain; Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Cardiovascular Diseases in the Development, Institut de Recerca Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, the Netherlands
Sergi Cesar
Pediatric Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain; Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Cardiovascular Diseases in the Development, Institut de Recerca Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, the Netherlands
Carles Díez-López
Cardiovascular Diseases Research Group, Bellvitge Biomedical Research Institute (IDIBELL), 08908 Hospitalet de Llobregat, Spain; Advanced Heart Failure and Heart Transplant Unit, Department of Cardiology, Bellvitge University Hospital, 08908 Hospitalet de Llobregat, Spain; Centro de Investigación Biomédica en Red, Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain
José Cruzalegui
Pediatric Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain; Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Cardiovascular Diseases in the Development, Institut de Recerca Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, the Netherlands
Nuria Díez-Escuté
Pediatric Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain; Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Cardiovascular Diseases in the Development, Institut de Recerca Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, the Netherlands
Patricia Cerralbo
Pediatric Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain; Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Cardiovascular Diseases in the Development, Institut de Recerca Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, the Netherlands
Fredy Chipa
Pediatric Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain; Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Cardiovascular Diseases in the Development, Institut de Recerca Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, the Netherlands
Irene Zschaeck
Pediatric Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain; Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Cardiovascular Diseases in the Development, Institut de Recerca Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, the Netherlands
Simone Grassi
Department of Health Sciences, Section of Forensic Medical Sciences, University of Florence, Largo Brambilla 3, 50134 Florence, Italy
Antonio Oliva
Department of Health Surveillance and Bioethics, Section of Legal Medicine, Fondazione Policlinico A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy
Norma Balderrábano
Cardiology Department, Children Hospital of Mexico Federico Gómez, México D.F, Mexico
Rocío Toro
Medicine Department, School of Medicine, University of Cádiz, 11003 Cádiz, Spain
Georgia Sarquella-Brugada
Pediatric Arrhythmias, Inherited Cardiac Diseases and Sudden Death Unit, Hospital Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain; Pediatric Arrhythmias, Genetic Cardiology and Sudden Death, Cardiovascular Diseases in the Development, Institut de Recerca Sant Joan de Déu, 08950 Esplugues de Llobregat, Spain; European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), 1105 AZ Amsterdam, the Netherlands; Medical Science Department, School of Medicine, Universitat de Girona, 17003 Girona, Spain
Oscar Campuzano
Centro de Investigación Biomédica en Red, Enfermedades Cardiovasculares (CIBERCV), 28029 Madrid, Spain; Medical Science Department, School of Medicine, Universitat de Girona, 17003 Girona, Spain; Institut d’Investigació Biomèdiques de Girona (IDIBGI), 17190 Salt, Spain; Corresponding author
Summary: Genetic analysis identified the cause of the disease in inherited arrhythmogenic syndromes. A clinically actionable genetic diagnosis requires an accurate interpretation following the current guidelines. Practically half of the genetic diagnoses remain inconclusive due to the identification of variants of uncertain significance. An update can help shed light on uncertain results. No specific time frame has been set for updating an ambiguous diagnosis. We carried out an analysis of the available reclassification/reinterpretation data concerning genetic diagnosis in inherited arrhythmogenic syndromes. We aim to determine an appropriate interval for updating a conclusive classification. Genetic diagnoses achieved without following current guidelines should be updated immediately. An ambiguous result obtained following the current guidelines should be updated no more than 5 years after the first analysis. There are still questions to be resolved regarding the legal responsibility or who should assume the economic cost of updating a genetic diagnosis.
