ABSTRACT
PURPOSE OF REVIEW: The aim is to review the most relevant findings published during the last year concerning clinical, genetic, pathogenic, and therapeutic advances in motor neuron disease, neuropathies, and neuromuscular junction disorders. RECENT FINDINGS: Studies on animal and cell models have improved the understanding of how mutated survival motor neuron protein in spinal muscular atrophy governs the pathogenetic processes. New phenotypes of SOD1 mutations have been described. Moreover, animal models enhanced the insight into the pathogenetic background of sporadic and familial amyotrophic lateral sclerosis. Novel treatment options for motor neuron disease have been described in humans and animal models. Considerable progress has been achieved also in elucidating the genetic background of many forms of inherited neuropathies and high clinical and genetic heterogeneity has been demonstrated. Mutations in MuSK and GFTP1 have been shown to cause new types of congenital myasthenic syndromes. A third type of autoantibodies (Lrp4) has been detected to cause myasthenia gravis. SUMMARY: Advances in the clinical and genetic characterization of motor neuron diseases, neuropathies, and neuromuscular transmission defects have important implications on the fundamental understanding, diagnosis, and management of these disorders. Identification of crucial steps of the pathogenetic process may provide the basis for the development of novel therapeutic strategies.
Subject(s)
Motor Neuron Disease , Neuromuscular Junction Diseases , Peripheral Nervous System Diseases , Animals , Disease Models, Animal , Humans , Motor Neuron Disease/classification , Motor Neuron Disease/genetics , Motor Neuron Disease/pathology , Motor Neuron Disease/therapy , Neuromuscular Junction Diseases/classification , Neuromuscular Junction Diseases/genetics , Neuromuscular Junction Diseases/pathology , Neuromuscular Junction Diseases/therapy , Peripheral Nervous System Diseases/classification , Peripheral Nervous System Diseases/genetics , Peripheral Nervous System Diseases/pathology , Peripheral Nervous System Diseases/therapyABSTRACT
Although muscle disease classically presents with proximal extremity weakness, some myopathic disorders, including several types of muscular dystrophy, result in predominantly, or exclusively, distal muscle involvement. Accurate diagnosis of these relatively uncommon conditions can be challenging for the clinician, because of both the unusual phenotype and the significant overlap in the clinical features of many of these entities. Advances in molecular genetics have permitted a tentative classification of these disorders and have led to the identification of the responsible gene lesion for several of these entities. This review summarizes current understanding of this interesting group of muscular dystrophies and briefly summarizes other myopathies that can present with distal weakness.
