Description:
<jats:title>Abstract</jats:title>
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<jats:title>Introduction</jats:title>
<jats:p>Danon disease (DD) is a rare multi-systemic disorder firstly described by Danon et al. in 1981 and characterized by a triad consisting with hypertrophic cardiomyopathy, skeletal myopathy, and intellectual disability. It is an inherited dominant X-linked condition, due to mutations in the lysosome-associated membrane protein 2 (LAMP2) gene. Typically, males present a more severe phenotype with earlier onset and rapid heart failure progression with extracardiac manifestations; female patients manifest a milder phenotype with later onset and isolated cardiac involvement. Female carriers may develop dilated cardiomyopathy (DCM). In recent years, it has been described a severe arrhythmogenic phenotype, particularly in women, with a high risk of sudden cardiac death (SCD).</jats:p>
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<jats:title>Case presentation</jats:title>
<jats:p>Case 1 is a 16 y.o. woman referred to our outpatient cardiomyopathies clinic, diagnosed with left ventricle (LV) hypertrophy on the basis of ECG and echocardiography, performed in 2016, in view of cutaneous nevus surgical exeresis. At echocardiographic evaluation we found an asymmetric LV hypertrophy with preserved LV ejection fraction (LVEF 65%). A cMRI was performed, showing mild LV thickening and left ventricular hypertrabeculation morphology, mainly in the LV lateral wall, but not all criteria for LV noncompaction (NC) were satisfied. There was no late gadolinium enhancement (LGE) accumulation. She underwent a genetic screening with inconclusive results, so we started a clinical outpatient follow-up showing no significant arrhythmias at ECG Holter and no limitation of physical activities. In 2021, when she was 21 yo, her father died suddenly and no autoptic examination was performed. A genetic exam was repeated, highlighting a LAMP2 gene mutation. In 2016 her 3 years older sister, Case 2, underwent a familiar screening. She had a long history of mild dyspnea occurring during exertion. Echocardiography showed asymmetric hypertrophy with marked thickening of infero-lateral wall (25 mm,) with normal systolic function (EF 70%). She underwent a cMRI, highlighting diffuse asymmetric hypertrophy (max 24 mm) with LGE in lateral wall and lower septum. First genetic test was nonconclusive but after her father's death another test was performed, demonstrating LAMP2 gene mutation. In 2021 a follow-up cMRI showed markedly reduced myocardial thickness of the apex, with a pattern of noncompaction myocardial. We found a LVEF at lower limits, depressed longitudinal function (MAPSE 8 mm) and manly severe progression of fibrotic degeneration. ECG Holter revealed premature ventricular complex, in absence of nonsustained ventricular tachycardia. Following the evolution of fibrosis, cardioverter defibrillator (ICD) implantation was performed. Case 1 was clinically stable during strict follow-up.</jats:p>
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<jats:title>Conclusion</jats:title>
<jats:p>Cardiac magnetic resonance imaging (cMRI) may be useful in arrhythmic risk stratification, accurate systolic dysfunction evaluation, and proper timing and indication for ICD implantation.</jats:p>
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