Características clínicas y pronóstico de la enfermedad de Danon. Análisis del registro multicéntrico español / Clinical findings and prognosis of danon disease. An analysis of the Spanish multicenter danon registry

Introducción y objetivos: La enfermedad de Danon (ED) es una enfermedad producida por mutaciones en el gen LAMP2. Se la considera una enfermedad multisistémica caracterizada por miocardiopatía hipertrófica con preexcitación e hipertrofia extrema, discapacidad intelectual, miopatía, presentación infantil y peor pronóstico en varones. Hay pocas series que permitan conocer las características clínicas y el pronóstico de la ED. Métodos: Se analizaron los registros clínicos de los pacientes con ED de 10 hospitales españoles. Resultados: Se incluyó a 27 pacientes (edad, 31 +/- 19 años; el 78% mujeres). Los varones mostraron una elevada prevalencia de manifestaciones extracardiacas -miopatía (80%), trastornos del aprendizaje (83%) y alteraciones visuales (60%)- que eran infrecuentes en las mujeres (el 5, el 0 y el 27% respectivamente). Aunque la miocardiopatía hipertrófica era la cardiopatía más habitual (61%), el grosor ventricular máximo fue 15 +/- 7 mm y 12 pacientes (10 mujeres) presentaron miocardiopatía dilatada. Solo 11 pacientes (49%) mostraron preexcitación y en 16 (65%) la enfermedad se inició después de los 20 años. Tras una mediana de seguimiento de 4 años [intervalo intercuartílico, 2-9], 4 varones (67%) y 9 mujeres (43%) fallecieron o se sometieron a trasplante. El daño cardiaco y los eventos adversos ocurrieron más tardíamente en las mujeres (37 +/- 9 frente a 23 +/- 16 años y 36 +/- 20 frente a 20 +/- 11 años). Conclusiones: Las características clínicas de la ED difieren sustancialmente de lo considerado tradicionalmente. La edad de presentación de la ED es más tardía, no se expresa como una enfermedad multisistémica en las mujeres y la preexcitación es poco frecuente

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

Clinical Findings and Prognosis of Danon Disease. An Analysis of the Spanish Multicenter Danon Registry.

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.