Hereditary motor neuropathies

Current Opinion in Neurology, vol. 33, pp. 568–574

Abstract

PURPOSE OF REVIEW: Hereditary motor neuropathies (HMN) comprise a broad genotypic and phenotypic spectrum of rare, progressively disabling diseases manifesting with length-dependent muscle weakness and atrophy. To date, more than half of the cases cannot be genetically explained. To provide symptomatic and disease-modifying treatments in the future, a better understanding of disease mechanisms is required. RECENT FINDINGS: By whole exome and genome sequencing, the discovery of several novel genes (SCO2, TDRKH, SPTAN1, CADM3, and SORD) involved in the pathogenesis of HMN has now relevantly changed the pathophysiological knowledge. This recent success in causative understanding has mainly been driven by the development of functional models including cell culture, animal, and patient-derived induced pluripotent stem cell platforms. These models have an important impact on therapeutic advances including broader approaches to prevent or reverse axonal degeneration and individualized gene silencing attempts using sequence-specific RNA degradation mechanisms. SUMMARY: In rare diseases such as HMN, the recent development of genetic sequencing and data interpretation methods has enabled a broader diagnostic approach, whereas treatment strategies are becoming more individualized. Significant milestones have been reached in the discovery of new genes, the establishment of functional disease models, and the preclinical development of mechanistic-based therapies.

Authors 2

1. Maike Franziska Dohrn Aachen Department of Neurology

   RWTH Aachen University · Universitätsklinikum Aachen · University of Miami · Dr. John T. Macdonald Foundation

   Affiliation as printed

   Department of Neurology, RWTH Aachen University Hospital, Aachen, Germany

   Dr. John T. Macdonald Foundation, Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA

2. Mario Saporta corresponding

   University of Miami · Dr. John T. Macdonald Foundation

   Affiliation as printed

   Department of Neurology, University of Miami Miller School of Medicine, Miami, Florida, USA

   Dr. John T. Macdonald Foundation, Department of Human Genetics and John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida, USA

   fax: +1 305 243 1249