Background: Mutations in the LMNA (lamin A/C) gene have been associated with neuromuscular and cardiac manifestations, but the clinical implications of these signs are not well understood. Objective: To learn more about the natural history of LMNA-related disease. Design: Observational study. Setting: 13 clinical centers in Italy from 2000 through 2018. Patients: 164 carriers of an LMNA mutation. Measurements: Detailed cardiologic and neurologic evaluation at study enrollment and for a median of 10 years of follow-up. Results: The median age at enrollment was 38 years, and 51% of participants were female. Neuromuscular manifestations preceded cardiac signs by a median of 11 years, but by the end of follow-up, 90% of the patients had electrical heart disease followed by structural heart disease. Overall, 10 patients (6%) died, 14 (9%) received a heart transplant, and 32 (20%) had malignant ventricular arrhythmias. Fifteen patients had gait loss, and 6 had respiratory failure. Atrial fibrillation and second- and third-degree atrioventricular block were observed, respectively, in 56% and 51% of patients with combined cardiac and neuromuscular manifestations and 37% and 33% of those with heart disease only. Limitations: Some of the data were collected retrospectively. Neuromuscular manifestations were more frequent in this analysis than in previous studies. Conclusion: Many patients with an LMNA mutation have neurologic symptoms by their 30s and develop progressive cardiac manifestations during the next decade. A substantial proportion of these patients will have life-threatening neurologic or cardiologic conditions. Primary Funding Source: None.

Cardiac and Neuromuscular Features of Patients with LMNA-Related Cardiomyopathy / G. Peretto, C. Di Resta, J. Perversi, C. Forleo, L. Maggi, L. Politano, A. Barison, S.C. Previtali, N. Carboni, F. Brun, E. Pegoraro, A. D'Amico, C. Rodolico, F. Magri, R.C. Manzi, A. Palladino, F. Isola, L. Gigli, T.E. Mongini, C. Semplicini, C. Calore, G. Ricci, G.P. Comi, L. Ruggiero, E. Bertini, P. Bonomo, G. Nigro, N. Resta, M. Emdin, S. Favale, G. Siciliano, L. Santoro, G. Sinagra, G. Limongelli, A. Ambrosi, M. Ferrari, P.G. Golzio, P.D. Bella, S. Benedetti, S. Sala. - In: ANNALS OF INTERNAL MEDICINE. - ISSN 0003-4819. - 171:7(2019 Oct 01), pp. 458-463. [10.7326/M18-2768]

Cardiac and Neuromuscular Features of Patients with LMNA-Related Cardiomyopathy

L. Maggi;F. Magri;G.P. Comi;S. Benedetti;
2019-10-01

Abstract

Background: Mutations in the LMNA (lamin A/C) gene have been associated with neuromuscular and cardiac manifestations, but the clinical implications of these signs are not well understood. Objective: To learn more about the natural history of LMNA-related disease. Design: Observational study. Setting: 13 clinical centers in Italy from 2000 through 2018. Patients: 164 carriers of an LMNA mutation. Measurements: Detailed cardiologic and neurologic evaluation at study enrollment and for a median of 10 years of follow-up. Results: The median age at enrollment was 38 years, and 51% of participants were female. Neuromuscular manifestations preceded cardiac signs by a median of 11 years, but by the end of follow-up, 90% of the patients had electrical heart disease followed by structural heart disease. Overall, 10 patients (6%) died, 14 (9%) received a heart transplant, and 32 (20%) had malignant ventricular arrhythmias. Fifteen patients had gait loss, and 6 had respiratory failure. Atrial fibrillation and second- and third-degree atrioventricular block were observed, respectively, in 56% and 51% of patients with combined cardiac and neuromuscular manifestations and 37% and 33% of those with heart disease only. Limitations: Some of the data were collected retrospectively. Neuromuscular manifestations were more frequent in this analysis than in previous studies. Conclusion: Many patients with an LMNA mutation have neurologic symptoms by their 30s and develop progressive cardiac manifestations during the next decade. A substantial proportion of these patients will have life-threatening neurologic or cardiologic conditions. Primary Funding Source: None.
Settore MED/26 - Neurologia
3-set-2019
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/678466
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