Epidemiology, natural course and registration of dystrophinopathies in the Netherlands

Duchenne Muscular Dystrophy is an X-chromosomal inherited condition, caused by
a mutation in the dystrophin gene. This protein has an important function in
stabilisation of the muscle membrane. In Duchenne patients this protein is
absent, leading to contraction-induced muscle damage. Clinically this results
in progressive muscle weakness, leading, without treatment, to a wheelchair
dependancy at approximately the age of ten and death due to respiratory failure
or a cardiomyopathy around the age of twenty.
With Becker Muscular Dystrophy there is also a mutation in the dystrophin gene.
However, in this condition there is dystrophin production, nut the dystrophin
is shorter than normal and only partially functional. As a result, the clinical
picture is milder than with Duchenne, ranging from wheelchair dependancy around
16 years of age to patients with a normal life expectancy.
The preceiding decades there have been several developments in the care for
Duchenne patients. Besides general improvements (vaccination, antibiotics) the
usage of corticosteroids and the start of home ventilation for Duchenne
patients are important developments that contribute to a longer mobility and a
better survival respectively.
Currently, there are eleven clinical phase I/II trials being planned, started
or recently ended for eleven medicines. Of these, the exon-skipping technology
is one of the most promising. Many of the possible therapies are mutation
specific, which makes it important to have an overview of which patient has
which mutation and is therefor eligable for a specific therapy or can
participate in a specific trial.

1. Description of the epidemology of dystrophinopathies in the Netherlands
2. Description of the natural course of dystrophinopathies in the Netherlands
and the influence of medical development on it.
3. The initiation of a database for patients willing to participate in future
research and/or trials.

Retrospective, observational cohortstudy. Inclusion of patients occurs through
the clinical-genetics database, internet, treating physicians, patient
organisations and the home ventilation centers. The expected duration of this
research project is 2 years.
After receiving the informed consent form, patients will receive a questionaire
and are asked to give permission to enquire about their medical records from
treating physicians. Following the results from the questionaire and the
medical record there will be a telephonic contact to discuss any remaining
questions/unclarities. The data will be stored in a national database. Besides
this, patients are asked to give permission to anonymously store their data in
the international TREAT-NMD database. By registration in these databases a
patient can be contacted in future to participate in possible (therapeutic)
research.

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