Distal Myopathies

The ENMC consortium on distal myopathies held its 3rd workshop in Naarden, the Netherlands, February 6-8^th, 2009. It was attended by 23 active participants from Finland, Japan, Israel, France, Germany, Australia, Sweden, Switzerland, Italy, Spain, Austria, UK and the USA. During the last 15 years the field of known and defined distal myopathies has expanded from a handful clinical entities to more than 16 genetically defined different diseases. For the majority of these diseases the underlying gene defect is established and the further disease mechanisms on the cellular level are currently explored. Due to this remarkable expansion in the number of distal myopathies the 3^rd workshop was concentrating on the diseases with involvement of the feature of the so called rimmed vacuoles on muscle biopsy and/or diseases caused by defects in genes needed for proteins in the contractile machinery of the muscle cell, the sarcomeric proteins.

The participants reported on a number of new mutations and new variations in the clinical features of the known distal myopathies. Other reports detailed newly discovered genes underlying distinct forms of distal myopathy, some of them yet unpublished. Considerable progress has been made in the clarification of the defects on the protein level and the molecular processes taking place in the muscle cells damaged by the mutations, even though these processes are very complex and not yet fully understood. Based on the existing knowledge some treatment options have already been tested in disease models for a few forms of distal myopathy, such as the GNE-mutated HIBM/DMRV disease. The results of these cellular and animal studies indicate a therapeutic opportunity that may be applicable to the human disease and soon open the way for clinical trials in patients. The workshop agreed on guidelines for diagnostic procedures for the clinicians, emphasizing the role of muscle imaging to complement and direct the diagnostics towards a molecular genetic diagnosis. These guidelines will be included in the extended report of the meeting to be submitted for publication in Neuromuscular Disorders.

A detailed report of these conclusions is now published in Neuromuscular Diseases (pdf)