Minor intellectual deficits are present in many patients in contrast with CDM and childhood onset DM1. Avoidant, obsessive-compulsive and passive-aggressive personality features have also been

reported (24, 25). Nocturnal apnoeic episodes and daytime sleepiness are a common manifestation. Gastrointestinal tract involvement covers irritable bowel syndrome, symptomatic gall stones and gamma-glutamyltransferase elevations. Finally, endocrine abnormalities include testicular atrophy, hypotestosteronism, insulin resistance with usually mild type-2 diabetes, thyroid dysfunction. Late-onset/asymptomatic DM1 In late-onset or asymptomatic Inhibitors,research,lifescience,medical patients (with low number of CTG repeats), only limited features are found on clinical and paraclinical assessment. Myotonia, weakness and excessive daytime sleepiness are rarely present. Before DNA tests became Inhibitors,research,lifescience,medical available, there were many examples of incorrect ascertainment, even when using markers such as EMG evidence of myotonia and slitlamp examination for the characteristic cataracts (26). In late-onset patients, the search for cataracts is helpful for identifying the transmitting person. Myotonic Dystrophy type 2 Clinical features The prevalence of DM2 is not well established, but estimated

to be similar to DM1 in European populations (27). In DM2 there Inhibitors,research,lifescience,medical are no distinct clinical subgroups although initially different phenotypes of DM2 were described: DM2/PROMM and PDM (5-7). The most important discrepancy between DM1 and DM2 is absence of a congenital or early-onset form in DM2 (12, 28) and the clinical presentation is a more continuum from early adult-onset Inhibitors,research,lifescience,medical severe form to very late–onset mild Inhibitors,research,lifescience,medical symptoms (paucisymptomatic). Clinically based ascertainment of DM2 patients is even more difficult because of the large phenotypic variability and a large number of individuals with milder symptoms who remain undiagnosed. Moreover, milder phenotypes with

prominent myalgia may easily be misdiagnosed as fibromyalgia (29) and patients with onset of slowly progressive proximal muscle weakness after age 70 years may not be referred STK38 for neuromuscular investigations. Further evidence that a large proportion of DM2 patients may be undiagnosed came from a recent study which indicate that co-segregation of heterozygous recessive CLCN1 mutations in DM2 patients is higher than GSK1120212 datasheet expected (30). In DM2 patients with co-segregating CLCN1 the severity of myotonia appear to be more evident either clinically or on EMG, thus these patients could be more easily identified and diagnosed than DM2 patients without the modifier allele. Consequently the majority of DM2 patients remains undiagnosed even in clinical centers with considerable experience with DM2.