Dilated cardiomyopathy (DCM) is a severe disease of heart muscle characterized by progressive ventricular dilation and impaired systolic function and is a major cause of congestive heart failure. Mutations of the Lamin A/C gene (LMNA) have been identified in ~8% of all DCM patients. Of the subset of inherited DCM patients with accompanying conduction disease, LMNA mutations are present in 40-50% of cases.
Emery-Dreifuss Muscular Dystrophy (EDMD) is characterized by early contractures of the elbows and Achilles tendons, slowly progressive muscle wasting and weakness, and late onset cardiomyopathy and arrhythmia. EDMD can be either X-linked or autosomal dominant in inheritance, and the vast majority of autosomal dominant cases are due to mutations in the LMNA gene.
One form of Limb Girdle Muscular Dystrophies (LGMD), LGMD1B is autosomal dominant with slowly progressive limb girdle muscular dystrophy, age-related atrioventricular cardiac conduction disturbances, and the absence of early contractures. Mutations of the LMNA gene are the basis of LGMD1B.
Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder that causes clinical features in childhood that are associated with premature aging. Such features may include hair loss, growth retardation, joint degeneration, and atherosclerosis. A vast majority of patients with HGPS have a LMNA G608G mutation, but other mutations in LMNA have been reported.
Mandibuloacral dysplasia (MAD) is a rare autosomal recessive disorder caused by LMNA mutations, which results in post-natal growth retardation, craniofacial and skeletal anomalies, and mottled cutaneous pigmentation.
Charcot-Marie-Tooth type 2B1 is an axonal autosomal recessive laminopathy and neuropathy, characterized predominantly by symmetrical distal muscle weakness and atrophy. Individuals initially present with depressed or absent tendon reflexes with weakness of foot dorsiflexion at the ankle.
Familial partial lipodystrophy (FLPD), Dunnigan type, is an autosomal dominant disease caused by mutations in LMNA and characterized by the progressive loss of subcutaneous fat from the extremities.
Deletions and/or duplications of the LMNA gene as causative of disease have been reported.