Familial mesial temporal lobe epilepsy (FMTLE) : a clinical and genetic study of 15 Italian families.
BACKGROUND
Familial mesial temporal lobe epilepsy (FMTLE) is characterized by prominent psychic and autonomic seizures, often without hippocampal sclerosis (HS) or a previous history of febrile seizures (FS), and good prognosis. The genetics of this condition is largely unknown.We present the electroclinical and genetic findings of 15 MTLE Italian families.


METHODS
FMTLE was defined when two or more first-degree relatives had epilepsy suggesting a mesial temporal lobe origin. The occurrence of seizures with auditory auras was considered an exclusion criterion. Patients underwent video-EEG recordings, 1.5-Tesla MRI particularly focused on hippocampal analysis, and neuropsychological evaluation. Genetic study included genotyping and linkage analysis of candidate loci at 4q, 18q, 1q, and 12q as well as screening for LGI1/Epitempin mutations.


RESULTS
Most of the families showed an autosomal dominant inheritance pattern with incomplete penetrance. Fifty-four (32 F) affected individuals were investigated. Twenty-one (38.8 %) individuals experienced early FS. Forty-eight individuals fulfilled the criteria for MTLE. Epigastric/visceral sensation (72.9 %) was the most common type of aura, followed by psychic symptoms (35.4 %), and déjà vu (31.2 %). HS occurred in 13.8% of individuals, three of whom belonged to the same family. Prognosis of epilepsy was generally good. Genetic study failed to show LGI1/Epitempin mutations or significative linkage to the investigated loci.


CONCLUSIONS
FMTLE may be a more common than expected condition, clinically and genetically heterogeneous. Some of the reported families, grouped on the basis of a specific aura, may represent an interesting subgroup on whom to focus future linkage studies.
Striano
Pasquale
P
Epilepsy Center, Department of Neurological Sciences Federico II University, Via Pansini 5, 80131, Napoli, Italy.
Gambardella
Antonio
A
Coppola
Antonietta
A
Di Bonaventura
Carlo
C
Bovo
Giorgia
G
Diani
Erica
E
Boaretto
Francesca
F
Egeo
Gabriella
G
Ciampa
Clotilde
C
Labate
Angelo
A
Testoni
Stefania
S
Passarelli
Daniela
D
Manna
Ida
I
Sferro
Caterina
C
Aguglia
Umberto
U
Caranci
Ferdinando
F
Giallonardo
Anna Teresa
AT
Striano
Salvatore
S
Nobile
Carlo
C
Michelucci
Roberto
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D025063:Chromosome Disorders / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D002874:Chromosome Mapping; D004252:DNA Mutational Analysis; D004569:Electroencephalography; D004833:Epilepsy, Temporal Lobe / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005799:Genes, Dominant / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D007558:Italy; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D019965:Neurocognitive Disorders / Q000235:genetics / Q000503:physiopathology; D010375:Pedigree; D012678:Sensation Disorders / Q000235:genetics / Q000503:physiopathology; D013702:Temporal Lobe / Q000473:pathology / Q000503:physiopathology*