The expanding world of myotonic dystrophies: how can they be detected?

Myotonic dystrophy (DM) comprises at least two genetically distinct forms, both of which are caused by expansions of microsatellite repeats. The expansion of a CTG repeat in the DMPK gene leads to the first genetic form (DM type 1), and the expansion of a CCTG repeat in the ZNF9 gene causes the second genetic form of the disease (DM type 2). In both cases, the repeat units may expand to several thousand repeats, and the number of repeats in the expanded alleles shows a high degree of meiotic and somatic instability. The unprecedented size of expansions and their dynamic nature still represents a diagnostic challenge, which has been facilitated using different methods and modifications since the identification of the underlying mutations of these disorders. Here, we present an overview of the basic methods described for the purpose of identification of the DM type 1 and DM type 2 expansions and discuss particular modifications and improvements implemented to extend the detection ranges of these methods. Our review focuses on the advantages and disadvantages of the methods based on Southern blot analysis, polymerase chain reaction amplification, and in situ hybridization techniques and also on the possibilities of preimplantation and prenatal genetic testing.