PP14.13 – 2765: SCN cluster deletions: More than the classic Dravet syndrome?

Abstract

Objective Dravet syndrome is a severe epileptic encephalopathy beginning in infancy. The characteristic electroclinical picture is well known. With the discovery of SCN1A, molecular confirmation is possible in 75% of the patients. In approximately 70% a mutation is found and in 3–5% a copy number variant (CNV). CNVs frequently involve deletions, which not only contain SCN1A but the whole SCN gene cluster. This cluster contains five sodium channel genes (SCN3A, SCN2A, SCN1A, SCNC9A and SCN7A) along with GRB14 and GALNT3. The aim of this study was to determine whether patients with a SCN cluster deletion show a more severe form of the Dravet syndrome or have a specific continuous gene deletion syndrome. Methods We retrospectively reviewed the files of children with a deletion of the SCN gene cluster. Results We report six patients with a SCN cluster deletion (5 confirmed by aCGH, one with MLPA). All patients have a large de novo deletion (mean 5.6 Mb, SD 2.5). The mean age of presentation was 14.8 w (SD 7.3 w). Four infants presented with myoclonus, one with a febrile status epilepticus and one with an afebrile focal seizure with secondary generalization. Three had dysmorphic features and an abnormal development prior to the onset of convulsions. All patients showed a disastrous course with a severe mental retardation, hypotonia, failure to thrive and therapy resistant epilepsy in infancy. Two patients died around the age of one year, one at the age of 15 years. Three patients (8m, 20m and 4y of age) are still in follow-up. Conclusion Patients with a SCN cluster deletion frequently show a more severe form than the classic Dravet syndrome phenotype. The slightly earlier presentations with myoclonic seizures, abnormal development prior to the onset of convulsions, severe developmental delay or dead in infancy are suggestive for the SCN cluster deletion syndrome.