DUCHENNE MUSCULAR DYSTROPHY - GENETICS: P.216Genetic carrier screening for Duchenne muscular dystrophy: the outcome of over forty years of genetic counselling on disease incidence in New South Wales Australia

Abstract

Duchenne muscular dystrophy (DMD), an X-linked recessive genetic disorder results in progressive muscle weakness, causing significant morbidity and mortality. Its incidence is approximately 1 in 5000 live male births. DMD is caused by mutations in the dystrophin gene, maternally inherited in approximately two thirds of affected boys. Female relatives have carrier risk. Clinical genetics services offer carrier testing ('cascade screening') and genetic counselling for relatives of DMD patients, enabling identification of carrier status and provision of reproductive options. In selected countries, reduced disease incidence is observed, possibly due to genetic counselling, cascade testing and prenatal diagnosis. To estimate changes in DMD incidence in NSW over 40 years and determine whether cascade screening and genetic counselling has led to this change. A retrospective study of 'probands' (live male and prenatal genetically diagnosed DMD) cases born within NSW from 2002-2012 will be conducted. Female carriers/mosaic cases are excluded from analysis. A retrospective clinical review of confounding factors potentially associated with DMD diagnosis will also be conducted, using clinical data sourced from all the major NSW paediatric hospitals. Data will be collated with results from a previous study reporting DMD incidence over a 25-year period from 1975 to 2001 inclusive. The combined results of these studies will be presented in the final analysis. Birth rate statistics will be sourced from the Australian Bureau of Statistics. The denominator for incidence will be live male birth rates. Data analysis is pending. However, we hypothesize that DMD incidence in NSW has reduced over the last 40 years owing to improvements in the methodology of genetic screening. This study will demonstrate the impact of robust genetic screening and counselling services, thus serving as a model for other health care systems globally.