Cardiac and Neuromuscular Features of Patients With LMNA-Related Cardiomyopathy.

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.