Generalised epilepsy with febrile seizures plus (GEFS(+)): molecular analysis in a restricted area.
OBJECTIVE
Mutation analysis of the SCN1B, SCN1A and GABRG2 genes in children affected by Genetic (Generalised) Epilepsy with Febrile Seizures plus (GEFS(+)) and their affected and some unaffected family members, coming from a restricted geographic area, was performed.


METHODS
Eight GEFS(+) families (58 members) diagnosed according to current GEFS(+) criteria were studied.


RESULTS
A heterozygous point mutation A2336G was detected in exon 13 of the SCNA1 gene in three affected members of one family but not in their unaffected relatives; a novel Ile1944Thr mutation was located within the intracellular C-terminal region of the SCNA1 gene in the proband and his healthy father in a second family. In the former family, the proband had dysmorphic features including large forehead, large nasal bridge, pointed nasal tip, triangular nostrils, deep nasolabial folds, thin upper lips with large mouth, congenital gingival hyperplasia with wide gingiva and mental retardation, abnormalities not previously listed in the clinical spectrum of GEFS(+).


CONCLUSIONS
Our study confirms that just a few GEFS(+) families have mutations in the five genes classically known and reinforces the genetic and also the phenotypic variability of GEFS(+) featuring clinical manifestations. Question rises whether the cognitive problems seen in two siblings and dysmorphic features in one of them may be related to the channelopathy as it occurs in other well-known ion channel disorders.
National Centre for Rare Diseases, Superior Institute of Health, Rome, Italy. agataritamaria.polizzi@iss.it
Agata
A
Polizzi
Gemma
G
Incorpora
Piero
P
Pavone
Martino
M
Ruggieri
Grazia
G
Annesi
Antonio
A
Gambardella
Lorenzo
L
Pavone
Aldo
A
Quattrone
D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004829:Epilepsy, Generalized / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010375:Pedigree; D017354:Point Mutation; D011963:Receptors, GABA-A / Q000235:genetics*; D003294:Seizures, Febrile / Q000235:genetics*; D015222:Sodium Channels / Q000235:genetics*; D062547:Voltage-Gated Sodium Channel beta-1 Subunit
C546279:GABRG2 protein, human; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; C568242:SCN1A protein, human; C470379:SCN1B protein, human; D015222:Sodium Channels; D062547:Voltage-Gated Sodium Channel beta-1 Subunit