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Título

Heart Failure in LMNA-related Emery Dreifuss Muscular Dystrophy

RESUMO

Case presentation: A 26-year-old female patient was admitted to the Cardiovascular Intensive Care Unit due to acute shortness of breath and hypoxia at rest, reporting exertional dyspnea over the past years. She was accompanied at the Neuromuscular Disorders outpatient clinic due to a past medical history of worsening muscle weakness and contractures beginning at the age of 3. These complaints were associated progressively with inability to walk without support and dysphagia. Her birth and family history, as well as her developmental milestones, were unremarkable. Examination revealed weakness affecting the proximal arms and distal legs with sparing of facial muscles, associated with scoliosis and contractures involving elbow and heel. Cardiorespiratory exam showed bilateral jugular vein distension and an irregular pulse. A through diagnostic work-up was conducted and a diagnosis of acute decompensated heart failure (HF) with reduced ejection fraction was made, associated with atrial fibrillation and bilateral pleural effusion. Laboratory assessment disclosed a serum creatine kinase level of 478 IU/L. Previous investigation was remarkable for a muscle biopsy with myopathic features and immunohistochemistry revealing deficiency of every tested protein (dystrofin, sarcoglycan, dysferlin, destroglycan and emerin). A genetic analysis was performed, disclosing one pathogenic variant in LMNA gene [c.83G>A (p.Arg28Gln)] shortly after the patient’s death due to refractory respiratory insufficiency, confirming a diagnosis of autosomal dominant Emery-Dreifuss muscular dystrophy (EDMD).

Discussion: EDMD commonly results from a defect of one or more proteins comprising the cell nuclear envelope. The classic clinical triad consists of early contractures, progressive muscle weakness and cardiac abnormalities. The two most common associated genes are EMD and LMNA. Mutations in LMNA most typically display an autosomal dominant inheritance pattern and de novo mutations are common. Mostly, these patients have a more severe disease course, and the incidence of cardiac involvement increases in an age-dependent manner. LMNA-related cardiomyopathy also carries a substantial risk of end-stage HF development, as seen in our patient.

Final Considerations: Despite its rareness, early diagnosis of LMNA-related muscular dystrophy is important for the detection of potentially fatal cardiac abnormalities. Thus, routine cardiac surveillance may prevent mortality in these young patients.

Palavras Chave

Emery-Dreifuss, Muscular Dystrophy, Heart Failure, Contractures