Abstracts

Rationale: More than 170 documented mutations in the sodium channel alpha subunit gene SCN1A are associated with a clinical spectrum of epilepsies with heterogeneous phenotypes (Generalized or Focal epilepsies), with GEFS+ on the mildest end of the spectrum, “post vaccinal” encephalopathy and severe myoclonic epilepsy of infancy or Dravet syndrome (SMEI) on the severest end. We reported a new mutation not described until now in an adult patient with mental retardation and seizures onset in adultdhood . Methods: Personal and familial medical history, video-EEG monitoring in awake and sleep, neuro-psychological, neuro-radiological, genetic and metabolic investigations were performed in our patient. SCN1A was analyzed by denaturing high performance liquid chromatography for sequence variations. DNA changes were characterized by automated DNA sequence analysis.Results: Patient mother’s presented adult onset pharmaco-sensible idiopathic generalized epilepsy. Our patient, a girl presented generalized “cryptogenic” epilepsy (possibly genetic or possibly symptomatic). Birth was normal, but mental retardation (IQ= 45, language acquired at 5 years, normal motor development apart cerebellar signs) with unkown etiology was noticed. Seizures begin at 20 years of age with unclear syndromic diagnosis (a febrile tonic, astatic seizures, generalized status). Epilepsy was pharmaco-resistant from the onset but lamotrigine induced a marked improvement. High resolution cerebral MRI and FDG-PET scan were normal. All genetic investigations (Ring 20 chromosome, Fragile X, Inv (dup) 15, Glut1 deficiency, Huntingtin…), skin and muscle biopsy were normal. However, etiology of this generalized epileptic encephalopathy was still considered as “possibly” genetic. For all above, we search for a mutation of GEFS+ genes. We identify a new de novo mutation in the SCN1A gene (c.5083delG/p.Val1695LysfsX1714X) not found in a control population of 100 subjects. Conclusions: Finding a mutation in SCN1A in an adult onset “cryptogenic” generalized epilepsy provide supporting evidence for an expand phenotype of epilepsies associated with SCN1A mutation. It seems important to investigate molecular diagnosis for determining the etiology of unclassified generalized epileptic “cryptogenic” encephalopathy because it avoid investigations looking for alternate etiologies and allows better choice of therapy (lamotrigine sodium channel blocker in this case).