6696 Genetic mutations in Duchenne Muscular Dystrophy Children in East of England

Objectives Duchenne muscular dystrophy, DMD, is an x-linked genetic condition known to be caused by mutations in the dystrophin gene. It presents in early childhood, with a variety of possible presentations, as described by the MUSCLE acronym.¹ Increasingly, new treatments for DMD have been developed to target specific classes of mutations, namely ataluren for nonsense mutations and exon-skipping therapy for deletion mutations. This retrospective database study explores three key areas: [1] Clinical presentation of children in the East of England sample, characterised using the MUSCLE acronym and current mobility status. [2] Frequency of different mutations present in the East of England sample, and the specific mutations present. [3] Carrier status of mothers to DMD children in the East of England sample. Methods This retrospective study examined hospital electronic records for 54 children with DMD from the region, under the care of the paediatric neuromuscular team at the Cambridge University Hospitals NHS Foundation Trust (CUHFT). Results Data was examined from 54 children, the majority of which between the ages of 6 and 15 and of White British ethnicity. The modal age of presentation was identified to be between the ages of 1 and 3 years. On classification with the MUSCLE acronym, the most frequent presentations were motor delay and unusual gait, in 19 and 11 children respectively. The other children presented with speech delay or due to a family history of DMD. 51% of children are currently ambulant. 65% of children were found to have a deletion mutation and 11% were found to have a nonsense mutation, with the remainder of children identified as having a point or duplication mutation, with percentages at 15% and 9% respectively. The commonest single exon deletion were exons 44 and 52. Information on carrier status was available for 35 children, of whom 19 children were identified as having a mother who is a carrier of a mutation in the dystrophin gene. Conclusion This is the first study describing the type of mutations in the East of England cohort. It highlights the well described common clinical presentations of children with DMD that health professionals need to be aware of. Further natural history studies are needed for accurate genotype/phenotype correlation. Detailed descriptions of the mutations are important as new treatments such as gene therapy trials have started in the UK and to guide future developments. Reference Van Ruiten H, Improving recognition of Duchenne muscular dystrophy: a retrospective case note review, September 2014.