PRRT2 phenotypic spectrum includes sporadic and fever-related infantile seizures.
OBJECTIVE
Benign familial infantile epilepsy (BFIE) is an autosomal dominant epilepsy syndrome characterized by afebrile seizures beginning at about 6 months of age. Mutations in PRRT2, encoding the proline-rich transmembrane protein 2 gene, have recently been identified in the majority of families with BFIE and the associated syndrome of infantile convulsions and choreoathetosis (ICCA). We asked whether the phenotypic spectrum of PRRT2 was broader than initially recognized by studying patients with sporadic benign infantile seizures and non-BFIE familial infantile seizures for PRRT2 mutations.


METHODS
Forty-four probands with infantile-onset seizures, infantile convulsions with mild gastroenteritis, and benign neonatal seizures underwent detailed phenotyping and PRRT2 sequencing. The familial segregation of mutations identified in probands was studied.


RESULTS
The PRRT2 mutation c.649-650insC (p.R217fsX224) was identified in 11 probands. Nine probands had a family history of BFIE or ICCA. Two probands had no family history of infantile seizures or paroxysmal kinesigenic dyskinesia and had de novo PRRT2 mutations. Febrile seizures with or without afebrile seizures were observed in 2 families with PRRT2 mutations.


CONCLUSIONS
PRRT2 mutations are present in >80% of BFIE and >90% ICCA families, but are not a common cause of other forms of infantile epilepsy. De novo mutations of PRRT2 can cause sporadic benign infantile seizures. Seizures with fever may occur in BFIE such that it may be difficult to distinguish BFIE from febrile seizures and febrile seizures plus in small families.
Florey Neuroscience Institutes, Melbourne, Australia.
Ingrid E
IE
Scheffer
Bronwyn E
BE
Grinton
Sarah E
SE
Heron
Sara
S
Kivity
Zaid
Z
Afawi
Xenia
X
Iona
Hadassa
H
Goldberg-Stern
Maria
M
Kinali
Ian
I
Andrews
Renzo
R
Guerrini
Carla
C
Marini
Lynette G
LG
Sadleir
Samuel F
SF
Berkovic
Leanne M
LM
Dibbens
D002675:Child, Preschool; D002819:Chorea / Q000175:diagnosis / Q000235:genetics; D020936:Epilepsy, Benign Neonatal / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D003294:Seizures, Febrile / Q000175:diagnosis / Q000235:genetics*
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C569370:PRRT2 protein, human