Clin Genet 2001: 59: 344–349 Printed in Ireland. All rights resered Short Report Epidemiology of myotonic dystrophy in Italy: re-apprisal after genetic diagnosis Siciliano G, Manca ML, Gennarelli M, Angelini C, Rocchi A, Iudice A, Miorin M, Mostacciuolo ML. Epidemiology of myotonic dystrophy in Italy: re-apprisal after genetic diagnosis. Clin Genet 2001: 59: 344–349. © Munksgaard, 2001 Before the discovery of the myotonic dystrophy (DM) gene, the DM epidemiological rates could not be accurately estimated. The aim of this study was to calculate the DM prevalence rates in Padova (North- East Italy) and in four provinces of North-West Tuscany (Central Italy) and, as of 30 June 1999, to do so using molecular genetic testing. A minimum prevalence rate of 9.31 ×10 -5 inhabitants was found, con- sistent with epidemiological rates worldwide, and more than two times as high as those of two previous studies conducted in the same areas during the era prior to molecular genetic testing. This study, the first in Italy since the discovery of the DM gene, under- lines the importance of direct genetic diagnosis of DM, especially in detecting mildly affected patients, a fundamental step in correctly esti- mating the risk of disease transmission in affected families. G Siciliano a , ML Manca a , M Gennarelli b , C Angelini c , A Rocchi a , A Iudice a , M Miorin d and ML Mostacciuolo d a Department of Neuroscience, University of Pisa, Pisa, b Human Genetics Laboratory, IRCCS-Fatebenefratelli, Brescia, c Department of Neurological and Psychiatric Sciences and d Department of Biology, University of Padova, Padova, Italy Key words: epidemiology – genetic diagnosis – myotonic dystrophy Corresponding author: Dr Gabriele Siciliano, M.D., Ph.D., Department of Neuroscience, Neurological Clinics, Via Roma 67, 56126 Pisa (I), Italy. Tel: +39-050-993046/ 993334; fax: +39-050-554808/550563; e-mail: gsicilia@med.unipi.it Received 1 November 2001, revised and accepted for publication 16 January 2001 Myotonic dystrophy (DM) is an autosomal domi- nant multisystem disorder characterized by myoto- nia, muscle atrophy, blepharoptosis, frontal balding, cataracts, gonadal atrophy, cardiomyopa- thy and mental impairment (1). The onset age and disease severity show marked variability both be- tween and within families. The cloning of the DM gene and identification of the mutation offer the possibility of direct gene testing, which improves clinical diagnostic accuracy. The genetic defect results from an unstable CTG trinucleotide repeat in the 3non-coding region of the DM protein kinase gene (DMPK) mapped on chromosome 19q13.3. In the normal population, the number of CTG repeats varies between 5 and 36 triplets, while from 50 to several thousand copies have been observed in DM patients (2). The (CTG) expan- sion is unstable at mitotic and meiotic levels, with a bias towards length increase in the successive generations, which accounts for the clinical antici- pation. In fact, the size of the trinucleotide repeat is related to onset age and clinical severity of disease (3). DM is the most frequent muscular dystrophy in adulthood with a prevalence rate of 2.2–5.5 per 100000 inhabitants in Western Europeans (1) and 5.5 per 100000 inhabitants in the Japanese popula- tion (4). DM is less prevalent in South-East Asian populations and is rare or absent in Africans (5). For the Italian population, only few reports are available on the epidemiology of DM, two of them performed in the same areas as in this study, and finding prevalence rates of 3.6 in the Veneto region (North-East Italy) (6) and 3.4 in North-West Tus- cany (Central Italy) (7), respectively. All these re- ports are antecedent to DM gene discovery. Therefore, we describe here a re-evaluation of DM prevalence rates in those two population samples of the Veneto and Tuscany regions using DNA analysis for DM mutation. Materials and methods Methods of ascertainment The ascertainment of all cases of MD in the two areas under consideration was carried out as follows: 344