Familial epilepsy and developmental dysphasia: description of an Italian pedigree with autosomal dominant inheritance and screening of candidate loci.
OBJECTIVE
To describe a familial epileptic condition combining a peculiar electro-clinical pattern with developmental language dysfunction in a large Italian kindred.


METHODS
We studied the clinical and neurophysiological features of a 4-generation family with 10 affected members (3 deceased). We also analysed in 7 affected and 7 healthy members microsatellite markers for 51 candidate loci for epilepsy, including 42 loci containing ion channel genes expressed in the brain, as well as the SPCH1 and SRPX2 loci.


RESULTS
Five of the seven living affected members (aged 20-58 years) had the full phenotype (seizures, EEG epileptiform abnormalities and dysphasia). The language dysfunction was the first symptom, becoming evident since the period of language development and mainly consisting of phonemic and syntactic paraphasias, difficulty of expression and reduced verbal fluency. The seizures had their onset between 2 and 23 years and were reported as epileptic falls (4) associated or not with myoclonic features, absences (3), tonic-clonic (1) and complex partial seizures (1). The seizures were easily controlled by antiepileptic treatment in all patients except one. In the five patients with a good response of seizures to treatment, the EEG tracings showed the coexistence of focal and generalized epileptiform abnormalities; in the refractory patient the interictal EEG demonstrated bilateral asynchronous fronto-temporal paroxysms with left predominance and ictal SEEG recording suggested a multifocal origin of the discharges. MRI of the brain was normal in all patients. Linkage analysis provided negative LOD scores for all the investigated loci.


CONCLUSIONS
We have described a novel familial pattern of epilepsy and developmental dysphasia which is not genetically linked to epilepsy or speech disorder loci, as documented by a candidate-gene linkage approach.
Michelucci
Roberto
R
Department of Neurosciences, Division of Neurology, Via Altura 3, Bellaria Hospital, 40139 Bologna, Italy. roberto.michelucci@ausl.bo.it
Scudellaro
Eva
E
Testoni
Stefania
S
Passarelli
Daniela
D
Riguzzi
Patrizia
P
Diani
Erica
E
Vazza
Giovanni
G
Vianello
Valeria
V
Scabar
Aldo
A
Mostacciuolo
Maria L
ML
Volpi
Lilia
L
Rubboli
Guido
G
Pinardi
Federica
F
Mancardi
Maria Margherita
MM
Tassinari
Carlo Alberto
CA
Nobile
Carlo
C
D000328:Adult; D017668:Age of Onset; D001037:Aphasia / Q000209:etiology* / Q000235:genetics*; D004569:Electroencephalography / Q000379:methods; D004827:Epilepsy / Q000150:complications* / Q000235:genetics*; D005192:Family Health; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D005799:Genes, Dominant; D008040:Genetic Linkage / Q000502:physiology; D006801:Humans; D007558:Italy; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics; D010375:Pedigree; D010641:Phenotype
C465448:FOXP2 protein, human; D051858:Forkhead Transcription Factors; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; C116881:SRPX2 protein, human