Multisystem disorder and limb girdle muscular dystrophy caused by LMNA p.R28W mutation

Abstract

Primary laminopathies caused by mutations in the LMNA gene typically display an extremely pleiotropic clinical presentation including cardiac, muscular and metabolic phenotypes. Additionally, many atypical laminopathies have been described combining features of two or more of the distinctive disorders or syndromes associated with LMNA mutations. We report on a 46-year-old female patient with a heterozygous p.R28W LMNA mutation, who presented with a novel clinical phenotype comprising severe limb-girdle muscular dystrophy, pronounced partial lipodystrophy, cardiac conduction defect, polycystic ovary disease and a metabolic syndrome with insulin-resistant diabetes mellitus and hypertriglyceridemia. On examination, her 23-year old daughter solely showed early signs of a LGMD phenotype.