A case report of a family with overlapping features of autosomal dominant febrile seizures and GEFS+.
Familial febrile seizures occur in both generalized epilepsy with febrile seizures plus (GEFS+) and autosomal dominant febrile seizures (ADFS). The literature largely separates families with GEFS+ from those with ADFS. However, there is clinical overlap, and families with ADFS also include individuals with afebrile seizures. The phenotypic spectrum of GEFS+ is broader now than when first described, resulting in unclear boundaries between these two familial syndromes. The purpose of this report is to highlight the phenotypic similarities of GEFS+ and ADFS. A multigenerational family with febrile and afebrile seizures is described and the clinical features are compared to those of previously reported GEFS+ and ADFS families. This family meets the requirements for both ADFS and the broader definition of GEFS+. Linkage analysis has shown no clear linkage to known febrile seizure or GEFS+ loci. Despite locus heterogeneity, identified mutations in reported GEFS+ have so far all been in sodium channel or gamma-aminobutyric acid (GABA)-receptor genes, with other modifier genes postulated to affect individual phenotypes. The two mutations identified in families with ADFS are in genes implicated in GEFS+, SCN1A, and GABRG2. We conclude that it is inappropriate to separate GEFS+ and ADFS at present given the clinical and genotypic overlap.
Hindocha
Neeti
N
Department of Clinical Neuroscience, Institute of Psychiatry, King's College London, London, United Kingdom. n.hindocha@iop.kcl.ac.uk
Nabbout
Rima
R
Elmslie
Frances
F
Makoff
Andrew
A
Al-Chalabi
Ammar
A
Nashef
Lina
L
D000293:Adolescent; D000328:Adult; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D004829:Epilepsy, Generalized / Q000150:complications* / Q000235:genetics; D005192:Family Health; D005260:Female; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics; D010641:Phenotype; D011963:Receptors, GABA-A / Q000235:genetics; D003294:Seizures, Febrile / Q000150:complications* / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics; D055815:Young Adult
C546279:GABRG2 protein, human; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; C568242:SCN1A protein, human; D015222:Sodium Channels