L.I.2: The ABC of autosomal recessive limb girdle muscular dystrophy

Abstract

Autosomal recessive limb girdle muscular dystrophy (LGMD2) is a group of heterogeneous muscle diseases that share several common denominators. Beside the same mode of inheritance, patients develop progressive weakness and wasting of their shoulder and pelvic girdle muscles whilst muscle biopsies generally show dystrophic histological features. Coming to a specific diagnosis in a patient with LGMD2 can be quite challenging. Diagnostic clues for the clinician can be the age of onset, the ethnic background, the involvement of respiratory muscles, the heart or other organ systems, the selective pattern of muscle pathology and immunoanalysis of the muscle biopsy. Next generation sequencing strategies, especially gene panel and exome sequencing approaches, are gradually replacing the often cumbersome gene by gene mutation analysis and should help to provide all patients with LGMD2 with a precise diagnosis over the next few years. The identification of the underlying genetic defect in almost 20 different forms of LGMD2 so far has helped to generate animal models and to study disease pathogenesis. Nevertheless there is currently no licensed drug for LGMD2 and treatment strategies focus on the improvement of symptoms. One of the biggest challenges is the low number of identified LGMD2 patients. Whereas in some forms of LGMD2 several hundred patients have been diagnosed, in other forms only very few families have been characterized. Over the coming years it will be important to develop a successful translational research pathway in LGMD2 by creating patient registries, developing standards of care and establishing validated outcome measures and disease biomarkers. These objectives can only be achieved through a close partnership between scientists, healthcare professionals, patient organizations, the pharmaceutical industry and regulators. The presentation will focus on the current stage of translational research approaches in LGMD2 and on future perspectives.