title: A novel inherited SCN1A mutation associated with different neuropsychological phenotypes: is there a common core deficit?
abstract: We report a three-generation, clinically heterogeneous family in which we identify a novel inherited splicing mutation of the SCN1A gene. Thirteen subjects were submitted to genetic analysis, clinical and instrumental examination, and neuropsychological assessment. In eight subjects, a heterozygous c.2946+5G>A donor splice site alteration in the SCN1A gene was found. Half of them had never had a seizure and showed normal EEG and cognitive profile, whereas the other half had a history of seizures and variable neuropsychological impairments ranging from moderate cognitive disabilities to mild visual-motor impairments. Different clinical phenotypes were identified, including generalized epilepsy with febrile seizure plus (GEFS+), Dravet syndrome, and partial epilepsy with febrile seizure plus (PEFS+). Remarkable clinical heterogeneity can be found among family members carrying the same SCN1A gene mutation. Variable involvement of visual-motor abilities might represent a neuropsychological feature which needs to be further explored in other familial cases.
authors.affiliation: Regional Center for Diagnosis and Treatment of Childhood Epilepsy, Department of Neuropsychiatry, Ospedali Riuniti, Ancona, Italy. Electronic address: claudiapassamonti.psi@gmail.com.
authors.forename: Claudia
authors.initials: C
authors.lastname: Passamonti
authors.affiliation: Neurology, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Petrelli
authors.affiliation: Pediatric Neurology Unit and Laboratories, Children's Hospital A. Meyer, University of Florence, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Mei
authors.affiliation: Neurology, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Foschi
authors.affiliation: Pediatric Neurology Unit and Laboratories, Children's Hospital A. Meyer, University of Florence, Italy.
authors.forename: Renzo
authors.initials: R
authors.lastname: Guerrini
authors.affiliation: Neurology, Polytechnic University of Marche, Ancona, Italy.
authors.forename: Leandro
authors.initials: L
authors.lastname: Provinciali
authors.affiliation: Regional Center for Diagnosis and Treatment of Childhood Epilepsy, Department of Neuropsychiatry, Ospedali Riuniti, Ancona, Italy.
authors.forename: Nelia
authors.initials: N
authors.lastname: Zamponi
mesh_terms: D000328:Adult; D000368:Aged; D002675:Child, Preschool; D003072:Cognition Disorders / Q000209:etiology / Q000523:psychology; D004831:Epilepsies, Myoclonic / Q000235:genetics* / Q000523:psychology; D004828:Epilepsies, Partial / Q000235:genetics / Q000523:psychology; D004829:Epilepsy, Generalized / Q000235:genetics / Q000523:psychology; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D020125:Mutation, Missense; D062550:NAV1.1 Voltage-Gated Sodium Channel / Q000235:genetics*; D009483:Neuropsychological Tests; D010375:Pedigree; D011597:Psychomotor Performance; D012326:RNA Splicing; D003294:Seizures, Febrile / Q000235:genetics / Q000523:psychology
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; C568242:SCN1A protein, human
keywords: Dravet syndrome spectrum; Neuropsychological phenotype; SCN1A gene