Ángela López-Sainz1, Joel Salazar-Mendiguchía2, Ana García-Álvarez3, Oscar Campuzano Larrea4, Miguel Ángel López-Garrido5, Luis García-Guereta6, María Eugenia Fuentes Cañamero7, Vicente Climent Payá8, María Luisa Peña-Peña9, Esther Zorio-Grima10, Paloma Jordá-Burgos3, Carles Díez-López11, Ramón Brugada12, José Manuel García-Pinilla5, Pablo García-Pavía13. 1. Unidad de Insuficiencia Cardiaca y Cardiopatías Familiares, Servicio de Cardiología, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Spain. 2. Servicio de Cardiología, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain; Departamento de Genética, Universidad Autónoma de Barcelona, Barcelona, Spain. 3. Servicio de Cardiología, Institut Clínic Cardiovascular, Hospital Clínic, Universitat de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clínic, Barcelona, Spain. 4. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Spain; Centro Genética Cardiovascular, Institut d'Investigacions Biomèdiques de Girona, Girona, Spain; Departamento Ciencias Médicas, Facultad de Medicina, Universidad de Girona, Girona, Spain. 5. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Spain; Servicio de Cardiología, Hospital Universitario Virgen de la Victoria, Málaga, Spain. 6. Servicio de Cardiología Pediátrica, Hospital Universitario La Paz, Madrid, Spain. 7. Servicio de Cardiología, Hospital Infanta Cristina, Badajoz, Spain. 8. Servicio de Cardiología, Hospital General Universitario de Alicante, Alicante, Spain; Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, Spain. 9. Unidad de Imagen y Cardiopatías Familiares, Servicio de Cardiología, Hospital Universitario Virgen del Rocío, Sevilla, Spain. 10. Unidad de Cardiopatías Familiares, Muerte Súbita y Mecanismos de Enfermedad (CaFaMuSMe), Instituto de Investigación Sanitaria La Fe, Valencia, Spain; Servicio de Cardiología, Hospital Universitario y Politécnico La Fe, Valencia, Spain. 11. Servicio de Cardiología, Hospital Universitari de Bellvitge, L'Hospitalet de Llobregat, Barcelona, Spain. 12. Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Spain; Centro Genética Cardiovascular, Institut d'Investigacions Biomèdiques de Girona, Girona, Spain; Departamento Ciencias Médicas, Facultad de Medicina, Universidad de Girona, Girona, Spain; Unidad Cardiopatías Familiares, Servicio de Cardiología, Hospital Universitari de Girona Dr. Josep Trueta, Girona, Spain. 13. Unidad de Insuficiencia Cardiaca y Cardiopatías Familiares, Servicio de Cardiología, Hospital Universitario Puerta de Hierro Majadahonda, Majadahonda, Madrid, Spain; Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Spain; Facultad de Ciencias de la Salud, Universidad Francisco de Vitoria (UFV), Pozuelo de Alarcón, Madrid, Spain. Electronic address: pablogpavia@yahoo.es.
Abstract
INTRODUCTION AND OBJECTIVES: Danon disease (DD) is caused by mutations in the LAMP2 gene. It is considered a multisystemic disease characterized by hypertrophic cardiomyopathy with pre-excitation and extreme hypertrophy, intellectual disability, myopathy, childhood presentation, and worse prognosis in men. There are scarce data on the clinical characteristics and prognosis of DD. METHODS: We analyzed the clinical records of patients with DD from 10 Spanish hospitals. RESULTS: Twenty-seven patients were included (mean age, 31 ± 19 years; 78% women). Male patients showed a high prevalence of extracardiac manifestations: myopathy (80%), learning disorders (83%), and visual alterations (60%), which were uncommon findings in women (5%, 0%, and 27%, respectively). Although hypertrophic cardiomyopathy was the most common form of heart disease (61%), the mean maximum wall thickness was 15 ± 7 mm and dilated cardiomyopathy was present in 12 patients (10 women). Pre-excitation was found in only 11 patients (49%). Age at presentation was older than 20 years in 16 patients (65%). After a median follow-up of 4 years (interquartile range, 2-9), 4 men (67%) and 9 women (43%) died or required a transplant. Cardiac disease and adverse events occurred later in women (37 ± 9 vs 23 ± 16 and 36 ± 20 vs 20 ± 11 years, respectively). CONCLUSIONS: The clinical characteristics of DD differ substantially from traditional descriptions: age at presentation of DD is older, the disease is not multisystemic in women, and pre-excitation is infrequent.
INTRODUCTION AND OBJECTIVES: Danon disease (DD) is caused by mutations in the LAMP2 gene. It is considered a multisystemic disease characterized by hypertrophic cardiomyopathy with pre-excitation and extreme hypertrophy, intellectual disability, myopathy, childhood presentation, and worse prognosis in men. There are scarce data on the clinical characteristics and prognosis of DD. METHODS: We analyzed the clinical records of patients with DD from 10 Spanish hospitals. RESULTS: Twenty-seven patients were included (mean age, 31 ± 19 years; 78% women). Male patients showed a high prevalence of extracardiac manifestations: myopathy (80%), learning disorders (83%), and visual alterations (60%), which were uncommon findings in women (5%, 0%, and 27%, respectively). Although hypertrophic cardiomyopathy was the most common form of heart disease (61%), the mean maximum wall thickness was 15 ± 7 mm and dilated cardiomyopathy was present in 12 patients (10 women). Pre-excitation was found in only 11 patients (49%). Age at presentation was older than 20 years in 16 patients (65%). After a median follow-up of 4 years (interquartile range, 2-9), 4 men (67%) and 9 women (43%) died or required a transplant. Cardiac disease and adverse events occurred later in women (37 ± 9 vs 23 ± 16 and 36 ± 20 vs 20 ± 11 years, respectively). CONCLUSIONS: The clinical characteristics of DD differ substantially from traditional descriptions: age at presentation of DD is older, the disease is not multisystemic in women, and pre-excitation is infrequent.
Authors: Alessia Argirò; Carolyn Ho; Sharlene M Day; Jolanda van der Velden; Elisabetta Cerbai; Sara Saberi; Jil C Tardiff; Neal K Lakdawala; Iacopo Olivotto Journal: J Am Heart Assoc Date: 2022-04-26 Impact factor: 6.106