PracticeUpdate

Next-Generation Sequencing Can Be Helpful in Diagnosing and Characterizing Limb Girdle Muscular Dystrophy Rare and subject tomisdiagnosis, limb girdle muscular dystrophy needs clinical evaluation

N ext-generation sequencing has been found to be helpful in diagnosing and characteriz- ing limb girdle muscular dystrophy (LGMD), a disease for which clinical trials are needed, accord- ing to two presentations at ICNMD 2018. Clinical trials are needed in LGMD Corrado Angelini, MD, of the Istituto di Ricovero e Cura a Carattere Scientifico San Camillo Hospital in Venice, Italy, told Elsevier’s PracticeUpdate , “Patients affected by LGMD are awaiting clinical treatment. Future developments may include the discovery of adeno-associated viral gene therapy or drugs able to counteract muscle atrophy.” Dr. Angelini explained that LGMD is progressive weakness with onset in the proximal limb girdle muscles. Age of onset varies from early childhood (not congenital) to late adulthood. Progression of muscle weakness is usually symmetrical and varies among individuals and genetic type. These disorders present a wide spectrum of mus- cle involvement and wasting, spanning from very severe forms with childhood onset and rapid pro- gression to relatively benign forms with late onset. A consortium meeting under the auspices of the European Neuromuscular Center, introduced a classification of LGMD based on molecular/genetic criteria. Autosomal-dominant loci were designated as LGMD 1, autosomal-recessive loci as LGMD 2. LGMD nomenclature adopted a progressive alpha- betical letter indicating the order of gene mapping identification.

A new classification was proposed in a 2017 European Neuromuscular Center meeting, where autosomal-dominant LGMD and recessive forms were named and numbered. This new classification includes dystrophies with proximal or disto-proximal features and high cre- atine kinase presentation with histopathological evidence at biopsy of fiber degeneration/regen- eration, fiber splitting, MRI imaging consistent with degenerative changes, and fibro-fatty infiltration. Inflammatory myopathies, myofibrillar myopathies, andmetabolicmyopathies are differential diagnoses that can be excluded on the basis of clinical features, muscle histopathology, and laboratory exams. It is important that inflammatory andmetabolic disorders be classified to informdifferential diagnosis because many of these diseases are treatable. LGMDs constitute a considerable fraction of all dystrophic individuals. Prevalence ranges from approximately eight to 70 cases per million inhabitants (1:123,000–1:14,500) depending on geographical area and ethnic origin. The frequency of each form of LGMD varies among populations. Clinical phenotypes due to LGMD gene mutations include severe childhood onset forms, distal and proximal myopathies, pseudometabolic myopa- thies, eosinophilic myositis, and hyperCKemia. Identifying suitable selection criteria is crucial in tri- als where participants are treated after identifying defective genes responsible for LGMD. Therapy is still unresolved in LGMD and care is mostly limited to rehabilitation, clinical follow-up of cardiac and respiratory complications.

Dr. Corrado Angelini

PRACTICEUPDATE CONFERENCE SERIES • ICNMD 2018 18