title: Early clinical features in Dravet syndrome patients with and without SCN1A mutations.
abstract: BACKGROUND
  SCN1A is the most clinically relevant epilepsy gene, most mutations causing Dravet syndrome (also known as severe myoclonic epilepsy of infancy or SMEI). We evaluated clinical differences, if any, between young patients with and without a SCN1A mutations and a definite clinical diagnosis of Dravet syndrome.
  
  
  METHODS
  Twenty-five patients with a diagnosis of Dravet Syndrome (7 males, 18 females; mean age at inclusion: 10.3; median: 9±7; range: 18 months-30 years) were retrospectively studied. A clinical and genetic study focusing on SCN1A was performed, using DHPLC, gene sequencing and MLPA to detect genomic deletions/duplications. A formal cognitive and behavioral assessment was available for all patients.
  
  
  RESULTS
  Analysis revealed SCN1A mutations comprising missense, truncating mutations and genomic deletions/duplications in eighteen patients and no mutation in seven. The phenotype of mutation positive patients was characterized by a higher number of seizures/month in the first year of life, an earlier seizure onset and a higher frequency of episodes of status epilepticus. The cognitive and behavioral profile was slightly worst in mutation positive patients.
  
  
  CONCLUSIONS
  These findings confirm that SCN1A gene mutations are strongly associated to a more severe phenotype in patients with Dravet syndrome.
authors.affiliation: Neurology Clinic, Polytechnic University of Marche, Ancona, Italy. cristinapetrelli84@alice.it
authors.forename: Cristina
authors.initials: C
authors.lastname: Petrelli
authors.forename: Claudia
authors.initials: C
authors.lastname: Passamonti
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cesaroni
authors.forename: Davide
authors.initials: D
authors.lastname: Mei
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
authors.forename: Nelia
authors.initials: N
authors.lastname: Zamponi
authors.forename: Leandro
authors.initials: L
authors.lastname: Provinciali
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000235:genetics / Q000473:pathology / Q000523:psychology; D042241:Early Diagnosis; D004831:Epilepsies, Myoclonic / Q000235:genetics* / Q000473:pathology* / Q000523:psychology; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation / Q000235:genetics*; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics*; D013577:Syndrome; D055815:Young Adult
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels