Familial neonatal seizures in 36 families: clinical and genetic features correlate with outcome

Grinton, Bronwyn E., Heron, Sarah E., Pelekanos, James T., Zuberi, Sameer M., Kivity, Sara, Afawi, Zaid, Williams, Tristiana C., Casalaz, Dan M., Yendle, Simone, Linder, Ilan, Lev, Dorit, Lerman-Sagie, Tally, Malone, Stephen, Bassan, Haim, Goldberg-Stern, Hadassa, Stanley, Thorsten, Hayman, Michael, Calvert, Sophie, Korczyn, Amos D., Shevell, Michael, Scheffer, Ingrid E., Mulley, John C. and Berkovic, Samuel F. (2015) Familial neonatal seizures in 36 families: clinical and genetic features correlate with outcome. Epilepsia, 56 7: 1071-1080. doi:10.1111/epi.13020

Author Grinton, Bronwyn E.
Heron, Sarah E.
Pelekanos, James T.
Zuberi, Sameer M.
Kivity, Sara
Afawi, Zaid
Williams, Tristiana C.
Casalaz, Dan M.
Yendle, Simone
Linder, Ilan
Lev, Dorit
Lerman-Sagie, Tally
Malone, Stephen
Bassan, Haim
Goldberg-Stern, Hadassa
Stanley, Thorsten
Hayman, Michael
Calvert, Sophie
Korczyn, Amos D.
Shevell, Michael
Scheffer, Ingrid E.
Mulley, John C.
Berkovic, Samuel F.
Title Familial neonatal seizures in 36 families: clinical and genetic features correlate with outcome
Journal name Epilepsia   Check publisher's open access policy
ISSN 1528-1167
Publication date 2015-07
Sub-type Article (original research)
DOI 10.1111/epi.13020
Open Access Status DOI
Volume 56
Issue 7
Start page 1071
End page 1080
Total pages 10
Place of publication Hoboken, NJ, United States
Publisher Wiley-Blackwell Publishing
Collection year 2016
Language eng
Formatted 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.

Significance:  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.
Keyword Clinical neurology
Ion channels
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
School of Medicine Publications
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