Expression of tuberin and hamartin in tuberous sclerosis complex-associated and sporadic cortical dysplasia of Taylor\'s balloon cell type

Focal cortical dysplasia (FCD) type IIB is a malformation of cortical development characterized by presence
of balloon cells. These cells share phenotypic features of giant cells found in tuberous sclerosis complex (TSC), but the relationship between FCD type IIB and TSC is not well established. TSC is an autosomal dominant disorder caused by mutation in either of two genes: TSC1, encoding hamartin, and TSC2, encoding tuberin. Both proteins form a complex inhibiting mTOR signalling pathway and thus regulate cell size and proliferation.
In this study, tuberin and hamartin expression was evaluated under a confocal microscope in six cases of Taylor\'s balloon cell type FCD. Three patients met the clinical criteria for TSC. In three other patients, TSC was excluded based on a panel of clinical and radiological examinations. Additionally, two cases of FCD type I and 3 samples of normal brain tissue were used as a reference group.
We found loss of tuberin and hamartin expression in FCD type IIB lesions from patients with TSC. In sporadic FCD type IIB cases, only a few tuberin and hamartin positive cells were detected in the white-grey matter junction and in deeper parts of the white matter. Cortical balloon cells showed loss of both tuberin and hamartin. In contrast, the expression of tuberin and hamartin in FCD type I samples was strong, similarly to normal brain tissue.
In conclusion, loss of TSC1 and TSC2 products expression in balloon cells of both cortical dysplasia type IIB in
TSC-related and sporadic patients suggests that FCD type IIB may represent the focal form of TSC.