Eight years' experience of direct molecular testing for myotonic dystrophy in Wales

Editor—Myotonic dystrophy is the most common muscular dystrophy of adult life, with a frequency of around 3-15 per 100 000 in most European populations.1 It is characterised by multisystemic involvement and extreme intra- and interfamilial variability in age at onset and degree of severity, which may range from subjects with cataract alone to severely affected infants with neonatal hypotonia, respiratory distress, and mental retardation; most patients have symptomatic onset in adult life. The disorder is now recognised as resulting from an expanded and unstable CTG trinucleotide repeat sequence in the 3′ untranslated region of the myotonic dystrophy protein kinase gene on chromosome 19,2-4 which has provided a highly accurate direct molecular test for diagnosis, replacing earlier testing by linkage analysis. Testing is now available as a service in medical genetic centres throughout the UK and in most other developed countries. However, in contrast to Huntington's disease,5 for which numerous studies have been reported and where established protocols for presymptomatic testing exist,6 there are only limited data for the experience of presymptomatic testing in myotonic dystrophy as a service, based mainly on the use of linked genetic markers7-9 and no specific guidance regarding counselling approaches. Most reports of molecular analysis as an aid to primary diagnosis have either been selected case reports or research studies.

In the present paper, we report our eight year results of direct mutation testing for myotonic dystrophy performed in Wales. The data provide a basis to discuss the outcomes and referral patterns for diagnostic, presymptomatic, and prenatal testing in our centre. Counselling issues related to presymptomatic testing are discussed in detail in an accompanying paper.10