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LMNA gene mutation linked to neuromuscular, cardiac conditions in most patients

Patients with LMNA gene mutations are likely to develop life-threatening neuromuscular or cardiac conditions, according to study results published in the Annals of Internal Medicine.

“The LMNA gene provides the code for the nuclear proteins lamin A and C, and mutations in this gene have been associated with clinical abnormalities in the heart and in skeletal muscle,” Giovanni Peretto, MD, of IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University in Milan, and colleagues wrote.

To provide more information about disease progression in patients with LMNA mutations, Peretto and colleagues conducted an observational study of patients with the mutation in 13 clinical centers in Italy between 2000 and 2018.

Researchers retrospectively collected data from each patient’s first clinical contact to their enrollment in the study. At enrollment, patients underwent extensive neurologic and cardiologic evaluations. During follow-up, neurologic evaluations were performed every year, and cardiologic evaluations were conducted every 6 months.

A total of 164 patients from 124 families were included in the study. Participants had a median age of 28 years at first clinical manifestation of the mutation and 38 years at enrollment. The median age at which skeletal muscle signs of the mutation occurred was 25 years, and the median age at which cardiac manifestations occurred was 36 years.

According to the researchers, 90% of patients had electrical heart disease followed by structural heart disease at the end of the follow-up period.

At the end of follow-up, 6% of patients died, 9% received a heart transplant and 20% had malignant ventricular arrhythmias. In addition, six patients experienced respiratory failure and 15 had gait loss.

Among patients with cardiac disease as a result of the mutation, 37% had atrial fibrillation and 33% had second-degree or third-degree atrioventricular blocks. For those with both cardiac and neuromuscular manifestations of the mutation, 56% had atrial fibrillation and 51% had second-degree or third-degree atrioventricular blocks.

Peretto and colleagues suggested that clinicians consider working with cardiologists and neurologists to manage patients with LMNA mutations.

“An advantage to this approach might be earlier identication of high-risk patients who might benet from earlier initiation of protective strategies, such as implantable cardioverter-debrillator therapy and referral to heart transplant centers,” they wrote. – by Erin Michael

Disclosures: Peretto reports no relevant financial disclosures. Please see study for all other authors’ relevant financial disclosures.