Abstracts

Mutations in the SCN1A gene are associated with severe myoclonic epilepsy in infancy (SMEI) and several related epilepsy phenotypes commencing in early infancy. These infantile epilepsies are typically refractory to standard anti-epileptic medication (AED) and may result in an epileptic encephalopathy with progressive cognitive impairment. Syndrome specific reports have suggested three medications or combinations which may be helpful. These are sodium valproate and topirimate, the bromides and stiripentol. Certain medications may exacerbate symptoms such as myoclonus. In November 2005 a service looking for mutations in SCN1A was established in our institution. Our aim was to determine if knowledge of a child[apos]s mutation status influenced prescription patterns., This service was available in Scotland at inception and UK wide in May 2006. SCN1A has 26 exons (7848bp) which are amplified in 40 fragments. A pre-screen is performed using Conformational Sensitive Capillary Electrophoresis (CSCE) and fragments containing apparent changes are sequenced. A detailed pre-test questionnaire helps us to attempt a syndromic classification. A joint molecular genetic and paediatric epileptology report is issued., To date we have tested and reported on 51 casese of infantile onset epilepsy and selected parents. To date all 5 cases of classical SMEI have identified mutations. 1/2 cases of SMEB have mutations and one child with a focal epilepsy has a mutation. All mutations are de novo. 5 individuals have had their medication altered as a result of the analysis. There is clinical improvement in 3 to date with reduction in seizure frequency and increased levels of alertness. Follow up is too short to comment on call cases., Identification of a mutation not only allows a family of a child with a devastating epilepsy to begin to understand why their child is affected but also allows consideration of medication changes both specific additions and withdrawals. Appropriate medication can reduce seizure frequency, potentially ameliorating the epileptic encephalopathy therefore reducing the acquired learning disability. This may be particulaly relevant to the young infant with suspected SMEI and frequent seizures who does not yet fulfill all the syndrome criteria. Prospective studies are ongoing with the use of the detailed questionnaire to determine phenotype and target testing to the most appropriate cases., (Supported by: Muir Maxwell Trust purchased the gene sequencer used for the analysis.)