Skeletal myopathy in a family with lamin A/C cardiac disease

Abstract

Background: The objective of this study was to evaluate patients with known hereditary cardiac conduction and myocardial disease (HCCMD) caused by a lamin A/C gene mutation for skeletal muscle involvement using magnetic resonance imaging (MRI) computed tomography (CT).

Methods: Twenty-one patients with the diagnosis of HCCMD were available for study. Of these 21, 11 had MRI scans of the lower legs. The 11 that had an MRI were compared to a control group of 17 healthy controls. In ten patients in whom MRI was contraindicated, CT was used for lower leg imaging and the gastrocnemius muscle was compared to an unaffected muscle.

Results: In patients with severe cardiac involvement defined as conduction system disease requiring pacemaker implant and CT instead of MRI, there was a significant difference in the composition of the unaffected muscle versus the gastrocnemius muscle, P<0.05. In the patients who underwent MRI, there was no statistical significance between the normal population and the study population. However, many study patients' images showed dramatic changes in the gastrocnemius muscle where there was definite replacement of muscle tissue by fibrofatty tissue.

Conclusions: Our results showed that patients with HCCMD can also present with skeletal muscle problems. The degree of skeletal muscle involvement is greater in HCCMD patients requiring implantable cardiac devices.

Keywords: Skeletal myopathy; cardiomyopathy; computed tomography (CT); magnetic resonance imaging (MRI).

Figure 1

T1-weighted imaging of calf muscle from a normal control (A) vs. a 32-year-old genotype-positive member of a family with 1p1-1q1 mutation in LMNA (B) that at this stage has produced non-sustained atrial arrhythmias. Note the mildly abnormal appearance of the medial head of the gastrocnemius muscle (arrow) in the patient that is not present in the control.

Figure 2

T1-weighted imaging of calf muscle (A) from an older LMNA patient, age 51 years, with intermediate-severity cardiomyopathy that has not yet required device implantation. There is striking abnormality of the entirety of both heads of the gastrocnemius bilaterally. (B) T1-weighted imaging with fat saturation in the same individual, demonstrating suppression of signal; this indicates fatty replacement in the affected regions; (C) delayed post-gadolinium imaging optimized for scar detection in the same individual shows enhancement in affected regions consistent with fibrosis. Together, these findings suggest fibrofatty replacement of the affected skeletal muscle. T, tibia; F, fibula; G, gastrocnemius; TA, tibialis anterior.

Figure 3

Calf image obtained with non-contrast computed tomography (CT) in a 47-year-old LMNA patient with advanced cardiac conduction disease requiring pacemaker implantation. There is bilateral, severe abnormality visible in the gastrocnemius (yellow arrow) and soleus (red arrow) compared to the unaffected adjacent skeletal muscle.