ABSTRACT
The LMNA gene encodes lamins A and C, components of the nuclear envelope. Its mutations cause a wide range of diseases named laminopathies involving either specific tissues in isolated fashion (cardiac and skeletal muscles, peripheral nerve, adipose tissue) or several tissues in a generalized way (premature ageing syndromes and related disorders). The striated muscle laminopathies include a variety of well clinically characterized disorders where cardiac muscle involvement represents the common feature that coexists with or without skeletal muscle disease. The cardiac disease of LMNA mutated patients is classically defined by conduction system and rhythm disturbances occurring early in the course of the disease, followed by dilated cardiomyopathy and heart failure. These features are life threatening and often responsible of cardiac sudden death. When associated, the skeletal muscle involvement is characterized by muscle weakness and wasting of variable topography with or without early joint contractures and spinal rigidity. Specific management of the cardiac disease to includes antiarrhythmic drugs, cardiac devices such as implantable cardioverter for primary and secondary prevention of sudden death, and heart transplantation at the end stage of heart failure. A large number of LMNA mutations leading to striated muscle laminopathies have been reported without so far any clear and definite phenotype/genotype relation. Finally, among the diverse hypotheses for pathomechanisms of LMNA mutations, the structural hypothesis suggesting a defective role of lamins A/C in maintaining the structural integrity of the nuclear envelope in striated muscles under constant mechanical stress is highly attractive to link the LMNA mutations and the cardiac disease.
