Limb girdle muscular dystrophies: clinical-genetical diagnostic update and prospects for therapy

Introduction: Limb Girdle Muscular Dystrophies (LGMD) are a clinically heterogeneous group of disorders presenting with a spectrum of disease severity ranging from severe childhood onset muscular dystrophy to adult-onset dystrophy. LGMDs include both dominant and recessive forms. Areas covered: The clinical phenotypes and diagnostic features of LGMD and specific features for each disease have been presented. An updated list of molecularly defined LGMD is provided. The instrumental, muscle imaging, and laboratory exams commonly used to assess final diagnosis are described, as well as recent genetic techniques and new diagnostic procedures, i.e. next generation sequencing, whole exome sequencing, RNA sequencing as compared to other techniques (e.g. protein analysis). The clinical management of patients and their main clinical respiratory and cardiac complications is covered. We also focus on current available future drugs or gene therapy and management by rehabilitation. Expert opinion: Many LGMD cases, who in the past remained for long time without a molecular diagnosis, nowadays can be investigated by next generation sequencing. Gene mutation analysis is always required to obtain a molecular diagnosis, and is fundamental to select patients for future pharmacological trials and gene therapies.