Focal cortical dysplasia: a genotype-phenotype analysis of polymorphisms and mutations in the TSC genes.
OBJECTIVE
Focal cortical dysplasia (FCD) is a common cause of pharmacoresistant human epilepsy. FCD has frequently been discussed as a "forme fruste" of tuberous sclerosis complex (TSC) because of the radiologic and histologic resemblance of dysplastic areas to tubers in TSC. Mutations or a germ-line predisposition in terms of increased polymorphisms in the TSC genes have been presumed to influence the pathogenesis of FCD. A detailed genotype-phenotype analysis of these patients has not been performed so far.


METHODS
In this study, 33 patients with FCD (among them 23 with FCD type 2 and 4 patients with multifocal FCD) were investigated (1) clinically as to dermatologic manifestations, retinal hamartoma, cardial rhabdomyoma, and renal angiomyolipoma, and (2) genetically by considering lesional brain tissue and blood using single strand conformation polymorphism (SSCP) electrophoresis and sequencing of the TSC1 and TSC2 genes.


RESULTS
In the clinical examinations, no subtle features of TSC could be detected in this large group of patients with FCD, pointing to the fact that this is a different patient group without clinical overlap. Several sequence alterations were found in the TSC1 and TSC2 genes in both lesional brain tissue and blood of FCD patients, however, in similar frequencies to that of the normal population. Moreover, most of these sequence alterations were silent.


CONCLUSIONS
This study shows that FCD-even multifocal FCD-is not caused by mutations in the TSC genes and seems not to be promoted by polymorphisms in the TSC genes. Therefore, FCD cannot be regarded as a "forme fruste" of TSC.
Gumbinger
Christoph
C
Epilepsy Center, University of Freiburg, Freiburg, Germany.
Rohsbach
Constantin B
CB
Schulze-Bonhage
Andreas
A
Korinthenberg
Rudolf
R
Zentner
Josef
J
Häffner
Monika
M
Fauser
Susanne
S
D000293:Adolescent; D000328:Adult; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D054220:Malformations of Cortical Development / Q000150:complications / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic / Q000235:genetics*; D055815:Young Adult
D002135:Calcium-Binding Proteins; C486009:TESC protein, human