Epidemiology of myotonic dystrophy in the molecular era: Implications for clinical trials and association studies

It is generally accepted that myotonic dystrophy (DM) as a whole is the most common type of muscular dystrophy among adult Caucasians. However, quite surprisingly, epidemiological studies on DM have been scarce, often incomplete and almost exclusively focused on myotonic dystrophy type 1 (DM1). Recent prevalence estimates of molecularly defined DM1 vary between 0.43 and 158 per 100,000 in different populations. Such a wide spanning range is the result of a very low prevalence rate among East-Asians as opposed to exceptionally high rates, due to founder effects, encountered in some inbred populations of European origin. However, prevalence rates among most Caucasian populations lie in between those extremes, whereas this disease is virtually absent in other ethnic groups. Such an uneven distribution of DM1 between distinct populations has no parallels in other muscular dystrophies. It can be explained by the fact that Caucasians more frequently harbor normal alleles at the high end of the CTG repeat size range within the Dmpk gene. These pre-mutated alleles, being highly unstable, represent a pool from which, after further expansion, new pathogenic DM1 mutations arise. The ethnic distribution of DM2 is even more selective, being exclusive, with a single exception, of Caucasian populations. Due to its recent characterization and difficulty in clinical and molecular diagnosis, there are only a few prevalence studies of DM2, indicating a minimum prevalence of 1/100,000. However, in some geographic areas, DM2 mutation may be as frequent as DM1. The ethnic distribution of DM1 and DM2 has suggested that the causative mutations may have arisen in Eurasian populations after their migration from Africa. A possible development of prevalence studies in the general population is the creation of disease registries that will allow to design studies on natural history of disease and to enroll representative patient cohorts for clinical trials. An additional utilization of a DM patient registry may be that of matching information with other disease registries for association studies, as recently proposed for DM and some types of cancer.