title: Familial neonatal seizures in 36 families: Clinical and genetic features correlate with outcome.
abstract: OBJECTIVE
  We evaluated seizure outcome in a large cohort of familial neonatal seizures (FNS), and examined phenotypic overlap with different molecular lesions.
  
  
  METHODS
  Detailed clinical data were collected from 36 families comprising two or more individuals with neonatal seizures. The seizure course and occurrence of seizures later in life were analyzed. Families were screened for KCNQ2, KCNQ3, SCN2A, and PRRT2 mutations, and linkage studies were performed in mutation-negative families to exclude known loci.
  
  
  RESULTS
  Thirty-three families fulfilled clinical criteria for benign familial neonatal epilepsy (BFNE); 27 of these families had KCNQ2 mutations, one had a KCNQ3 mutation, and two had SCN2A mutations. Seizures persisting after age 6 months were reported in 31% of individuals with KCNQ2 mutations; later seizures were associated with frequent neonatal seizures. Linkage mapping in two mutation-negative BFNE families excluded linkage to KCNQ2, KCNQ3, and SCN2A, but linkage to KCNQ2 could not be excluded in the third mutation-negative BFNE family. The three remaining families did not fulfill criteria of BFNE due to developmental delay or intellectual disability; a molecular lesion was identified in two; the other family remains unsolved.
  
  
  CONCLUSIONS
  Most families in our cohort of familial neonatal seizures fulfill criteria for BFNE; the molecular cause was identified in 91%. Most had KCNQ2 mutations, but two families had SCN2A mutations, which are normally associated with a mixed picture of neonatal and infantile onset seizures. Seizures later in life are more common in BFNE than previously reported and are associated with a greater number of seizures in the neonatal period. Linkage studies in two families excluded known loci, suggesting a further gene is involved in BFNE.
authors.affiliation: Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: Bronwyn E
authors.initials: BE
authors.lastname: Grinton
authors.affiliation: Epilepsy Research Program, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia.|Sansom Institute for Health Research, University of South Australia, Adelaide, South Australia, Australia.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Heron
authors.affiliation: Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.|Department of Neurology, Royal Brisbane & Women's Hospital, Herston, Queensland, Australia.|UQ Centre for Clinical Research, The University of Queensland, Herston, Queensland, Australia.
authors.forename: James T
authors.initials: JT
authors.lastname: Pelekanos
authors.affiliation: Paediatric Neurosciences Research Group, Fraser of Allander Neurosciences Unit, Royal Hospital for Sick Children, Glasgow, United Kingdom.
authors.forename: Sameer M
authors.initials: SM
authors.lastname: Zuberi
authors.affiliation: Epilepsy Unit, Schneider Children's Medical Center of Israel, Petach Tikvah, Israel.
authors.forename: Sara
authors.initials: S
authors.lastname: Kivity
authors.affiliation: Tel-Aviv University Medical School, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Zaid
authors.initials: Z
authors.lastname: Afawi
authors.affiliation: Department of Genetic Medicine, SA Pathology, Women's and Children's Hospital, North Adelaide, South Australia, Australia.
authors.forename: Tristiana C
authors.initials: TC
authors.lastname: Williams
authors.affiliation: Department of Paediatrics, Mercy Hospital for Women, Heidelberg, Victoria, Australia.
authors.forename: Dan M
authors.initials: DM
authors.lastname: Casalaz
authors.affiliation: Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: Simone
authors.initials: S
authors.lastname: Yendle
authors.affiliation: Pediatric Neurology Unit, Wolfson Medical Center, Holon, Israel.|Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.|Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Holon, Israel.
authors.forename: Ilan
authors.initials: I
authors.lastname: Linder
authors.affiliation: Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.|Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Holon, Israel.|Institute of Medical Genetics, Wolfson Medical Center, Holon, Israel.
authors.forename: Dorit
authors.initials: D
authors.lastname: Lev
authors.affiliation: Pediatric Neurology Unit, Wolfson Medical Center, Holon, Israel.|Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.|Metabolic-Neurogenetic Clinic, Wolfson Medical Center, Holon, Israel.
authors.forename: Tally
authors.initials: T
authors.lastname: Lerman-Sagie
authors.affiliation: Department of Neurosciences, Royal Children's Hospital, Brisbane, Queensland, Australia.
authors.forename: Stephen
authors.initials: S
authors.lastname: Malone
authors.affiliation: Pediatric Neurology and Development Unit, Tel Aviv Sourasky Medical Center, Dana Children's Hospital, Tel-Aviv, Israel.
authors.forename: Haim
authors.initials: H
authors.lastname: Bassan
authors.affiliation: Epilepsy Unit, Schneider Children's Medical Center of Israel, Petach Tikvah, Israel.
authors.forename: Hadassa
authors.initials: H
authors.lastname: Goldberg-Stern
authors.affiliation: Department of Paediatrics, School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Stanley
authors.affiliation: Department of Neurology, Royal Children's Hospital, Flemington, Victoria, Australia.|Department of Paediatrics, Monash Medical Centre, Clayton, Victoria, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Hayman
authors.affiliation: Department of Neurosciences, Royal Children's Hospital, Brisbane, Queensland, Australia.
authors.forename: Sophie
authors.initials: S
authors.lastname: Calvert
authors.affiliation: Department of Neurology, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: Amos D
authors.initials: AD
authors.lastname: Korczyn
authors.affiliation: Department of Pediatrics & Neurology, McGill University, Montreal, Quebec, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Shevell
authors.affiliation: Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.|Department of Paediatrics, Royal Children's Hospital, The University of Melbourne, Flemington, Victoria, Australia.|The Florey Institute of Neuroscience and Mental Health, Heidelberg, Victoria, Australia.
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.affiliation: Department of Genetic Medicine, SA Pathology, Women's and Children's Hospital, North Adelaide, South Australia, Australia.|School of Molecular and Biomedical Science, The University of Adelaide, Adelaide, South Australia, Australia.|School of Paediatrics and Reproductive Health, The University of Adelaide, Adelaide, South Australia, Australia.
authors.forename: John C
authors.initials: JC
authors.lastname: Mulley
authors.affiliation: Epilepsy Research Centre, Department of Medicine, Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia.
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
mesh_terms: D015331:Cohort Studies; D020936:Epilepsy, Benign Neonatal / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D051658:KCNQ2 Potassium Channel; D008297:Male; D010375:Pedigree; D012640:Seizures; D016896:Treatment Outcome
chemical_list: D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human
keywords: Clinical neurology; Epilepsy; Genetics; Ion channels; Neonatal seizures