Report of the 115th ENMC workshop: DM2/PROMM and other myotonic dystrophies: 3rd Workshop, 14–16 February 2003, Naarden, The Netherlands

Abstract

Myotonic dystrophy (DM1, Steinert’s disease) has been known for about 100 years. Its core features are myotonia, muscle weakness, and cataracts [1]. In 1994 another disorder was published with similar core features but lacking the DM1 mutation [2,3]. The name given to this disorder was proximal myotonic myopathy (PROMM, OMIM *160900). The first ENMC workshop on PROMM in 1997 established the clinical criteria for PROMM [4]. Prior to the second ENMC Workshop on PROMM in 2000, a major breakthrough had been accomplished when, in 1998, Ranum and Day [5] described the mapping of a new genetic locus in a large Minnesota family with myotonic dystrophy-like features on chromosome 3q21. This locus was named DM2. As a result, a new nomenclature emerged and the locus for myotonic dystrophy/Steinert’s disease was renamed DM1 [6]. Subsequent work showed that most PROMM families also mapped to the DM2 locus, whereas another smaller group of PROMM families appeared not to be linked to this locus. One separately described family with marked proximal atrophies, called proximal myotonic dystrophy [7], also mapped to the DM2 locus [8], and the workshop adopted the term myotonic dystrophy type 2 (DM2) for all the progressive myotonic multiorgan disorders linked to the DM2 locus. The clinical course of DM2 appeared to be more favourable compared to DM1. Families with DM2 did not have the severe congenital form of illness that occurs in DM1. Abnormalities in the social and cognitive abilities of adults with DM2 were typically mild or absent, and there was no prominent weakness of the facial and bulbar muscles. In DM2 the manual skills largely remained intact, and hypersomnia and mental retardation were not prominent findings. All these characteristic features of DM2 have not changed since the first ENMC Workshop[4]. They are still valid. In the advent of this 3rd workshop on DM2/PROMM, the definitive milestone of research efforts was achieved in 2001 with the identification of the mutation underlying DM2 by Ranum and Day, in collaboration with Ricker [9]. The mutation is a huge (CCTG)n microsatellite repeat expansion in the first intron of the ZNF9 gene and is thus similar to the (CTG)n repeat causing DM1. The aims with this 3rd ENMC Workshop on DM2/PROMM were: