Cardiac and Neuromuscular Features of Patients with LMNA-Related Cardiomyopathy

Italian Network for Laminopathies (NIL)

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalAnnals of Internal Medicine
DOIs
Publication statusE-pub ahead of print - Sep 3 2019

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Lamin Type A
Cardiomyopathies
Neuromuscular Manifestations
Heart Diseases
Nervous System
Mutation
Atrioventricular Block
Neurologic Manifestations
Natural History
Gait
Respiratory Insufficiency
Atrial Fibrillation
Italy
Observational Studies
Cardiac Arrhythmias
Transplants

Cite this

Cardiac and Neuromuscular Features of Patients with LMNA-Related Cardiomyopathy. / Italian Network for Laminopathies (NIL).

In: Annals of Internal Medicine, 03.09.2019.

Research output: Contribution to journalArticle

@article{dd4df20cc721485e92382c5f4175deee,
title = "Cardiac and Neuromuscular Features of Patients with LMNA-Related Cardiomyopathy",
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.",
author = "{Italian Network for Laminopathies (NIL)} and Giovanni Peretto and {Di Resta}, Chiara and Jacopo Perversi and Cinzia Forleo and Lorenzo Maggi and Luisa Politano and Andrea Barison and Previtali, {Stefano C} and Nicola Carboni and Francesca Brun and Elena Pegoraro and Adele D'Amico and Carmelo Rodolico and Francesca Magri and Manzi, {Rosa C} and Alberto Palladino and Franco Isola and Lorenzo Gigli and Mongini, {Tiziana E} and Claudio Semplicini and Chiara Calore and Giulia Ricci and Comi, {Giacomo P} and Lucia Ruggiero and Enrico Bertini and Paolo Bonomo and Gerardo Nigro and Nicoletta Resta and Michele Emdin and Stefano Favale and Gabriele Siciliano and Lucio Santoro and Gianfranco Sinagra and Giuseppe Limongelli and Alessandro Ambrosi and Maurizio Ferrari and Golzio, {Pier G} and Bella, {Paolo Della} and Sara Benedetti and Simone Sala",
year = "2019",
month = "9",
day = "3",
doi = "10.7326/M18-2768",
language = "English",
journal = "Annals of Internal Medicine",
issn = "0003-4819",
publisher = "American College of Physicians",

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TY - JOUR

T1 - Cardiac and Neuromuscular Features of Patients with LMNA-Related Cardiomyopathy

AU - Italian Network for Laminopathies (NIL)

AU - Peretto, Giovanni

AU - Di Resta, Chiara

AU - Perversi, Jacopo

AU - Forleo, Cinzia

AU - Maggi, Lorenzo

AU - Politano, Luisa

AU - Barison, Andrea

AU - Previtali, Stefano C

AU - Carboni, Nicola

AU - Brun, Francesca

AU - Pegoraro, Elena

AU - D'Amico, Adele

AU - Rodolico, Carmelo

AU - Magri, Francesca

AU - Manzi, Rosa C

AU - Palladino, Alberto

AU - Isola, Franco

AU - Gigli, Lorenzo

AU - Mongini, Tiziana E

AU - Semplicini, Claudio

AU - Calore, Chiara

AU - Ricci, Giulia

AU - Comi, Giacomo P

AU - Ruggiero, Lucia

AU - Bertini, Enrico

AU - Bonomo, Paolo

AU - Nigro, Gerardo

AU - Resta, Nicoletta

AU - Emdin, Michele

AU - Favale, Stefano

AU - Siciliano, Gabriele

AU - Santoro, Lucio

AU - Sinagra, Gianfranco

AU - Limongelli, Giuseppe

AU - Ambrosi, Alessandro

AU - Ferrari, Maurizio

AU - Golzio, Pier G

AU - Bella, Paolo Della

AU - Benedetti, Sara

AU - Sala, Simone

PY - 2019/9/3

Y1 - 2019/9/3

N2 - 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.

AB - 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.

U2 - 10.7326/M18-2768

DO - 10.7326/M18-2768

M3 - Article

C2 - 31476771

JO - Annals of Internal Medicine

JF - Annals of Internal Medicine

SN - 0003-4819

ER -