Myotonic dystrophy: present management, future therapy

Number 99
Date 9 November 2001

Location: Naarden, The Netherlands


This Workshop, the first held by the ENMC on the topic of myotonic dystrophy, had as its themes the issue of how optimal management can be defined and delivered to patients with myotonic dystrophy, and how we can plan foundations for trials of therapy, whether symptomatic or, in the future, possibly more definitive.
The needs of myotonic dystrophy patients and families were first put into perspective by Margaret Bowler, of the UK Myotonic Dystrophy Support Group, who described the key symptoms from the viewpoint of the patient and carer. The importance of considering myotonic dystrophy as a childhood as well as an adult disorder were then outlined by Christine de Die-Smulders, who emphasised the learning and behavioural problems in this group, not all of whom had clear features of myotonic dystrophy at birth.
The second session concentrated on neuromuscular aspects of myotonic dystrophy. The core diagnostic procedures were first outlined and it was agreed that these had become considerably simplified, with a combination of clinical assessment and DNA analysis providing the necessary information in most cases, though the situation was still provisional for the few "DM type 2" families not showing the chromosome 19 DNA abnormality.
Discussion next focussed on assessment protocols; it was recognized that there was a need for simple protocols (e.g. Cardiff protocol) for regular patient assessments, as well as for a fuller baseline database and research orientated assessments. In respect to aspects of physical disability myotonic dystrophy patients had much to gain from measures also applicable to other neurological disorders, notably those improving mobility and involving the social and domestic aspects.
The following sessions debated how best to manage the important non-neuromuscular systemic aspects of the disorder, in particular the cardiac aspects, which were recognized as a major cause of serious illness and mortality. Results of the Paris group in particular confirmed the value of regular ECG as the foundation, with more specialist tests being necessary if this were abnormal or if relevant symptoms were present. Preliminary results of a study of early pacemaker insertion were encouraging.
Anaesthetic/surgical problems were then discussed, with a general agreement on measures required, but with both this and cardiac management there remained serious lack of awareness among relevant clinicians.
Other important systemic aspects included gastrointestinal problems, where a need for trials of possible agents was identified; somnolence, where promising preliminary studies required confirmation by full trials; and hormonal and pregnancy aspects,

Genetic counselling was discussed as part of the overall management and risk figures were presented for different situations, together with the approaches needed for genetic testing of healthy family members.
The important topic of providing information received detailed discussion, with special emphasis on Internet based information and providing this direct to patients as a way of helping to both improve their management and also in educating professionals. This approach was proving successful in both UK and other countries.
The second part of the Workshop opened with descriptions of major scientific advances which have radically increased our understanding of how the genetic change in myotonic dystrophy actually produces disease. These advances have already produced animal models which can be used both for further understanding and also in assessing further potential therapeutic agents that may not be ready or appropriate for testing in patients. Already trials of a number of agents on patients have taken place in relation to specific symptoms; however as yet none has shown a clear effect on the course of this disorder and it was recognised that it would still be some years before this stage would be reached.
The final session discussed the need for establishing reproducible and standardised assessment protocols that would allow accurate measurement of the natural history of the disorder and that could provide the foundations for large-scale clinical trials. Here it was clear that considerable further work was needed.
The Workshop agreed that it was important to form an ENMC Consortium, the Myotonic Dystrophy Management and Therapy Consortium, which would meet again in two years to assess progress, and which would undertake a series of co-ordinated activities meanwhile.
It was clear that the wider development of trials would require additional expertise from basic research, statistics and other areas, and that co-ordination would be needed with those planning trials for other neuromuscular disorders. This will be discussed among the Workshop members and ENMC, particularly in relation to possibilities for short and longer-term support.

An extended report of this meeting is published in Neuromuscular Disorders, Volume 12, No.6, August 2002

Prof. Peter Harper, Cardiff (UK)
Dr. Baziel van Engelen, Nijmegen (The Netherlands)
Prof. Bruno Eymard, Paris (France)
Dr. Douglas Wilcox, Glasgow (UK)