Cardiac involvement in laminopathies–short invited review

Mutations in lamins, which are ubiquitous nuclear intermediate filaments, lead to a variety of disorders, described as laminopathies or nuclear envelopathies, that include both X-linked and autosomal dominant forms of Emery-Dreifuss muscular dystrophy (EDMD), dilated cardiomyopathy with conduction system defects (DCM-CD), limb girdle muscular dystrophy 1B (LGMD1B) with atrioventricular conduction disturbances, Dunnigan-type familial partial lipodystrophy (FPLD), mandibuloacral dysplasia (MAD), and autosomal recessive forms of axonal Charcot-Marie-Tooth (ARCMT2, CMT2B) and progeria syndromes. Cardiac involvement in laminopathies can be isolated or more frequently associated with muscle involvement. The vast majority of patients develop dysrhythmias after the age of 30 years, and many undergo pace maker (P.M.) or cardioverter defibrillator implantation; heart failure is relatively frequent after the age of 50 but it occurs less commonly than dysrhythmias. Both tachy-arrhythmias and brady-arrhythmias may occur also in LMNA mutated patients presenting a congenital or early onset of the disease. Sudden cardiac death (SCD) is the modality of exitus most frequently observed even in implanted patients, indicating that subjects carrying LMNA gene mutations are at high risk of sudden death and that P.M. implantation is unable to protect them against this dramatic event. The identification of parameters able to stratify the patients at risk is of considerable utility in clinical practice.