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.