Neurologic phenotypes in tuberous sclerosis complex

Tuberous Sclerosis Complex (TSC) is a disorder of cell migration, proliferation and differentiation, resulting from mutations in TSC1, the gene on chromosome 9q34 and in TSC2, the gene on chromosome 16p13. Cortical tubers constitute the hallmark of the disease and are pathognomonic of cerebral TSC. The number and the localisation of cortical tubers may account for the variability of the neurobehavioural phenotype observed in TSC patients. Symptoms of cortical tubers include seizures, mental retardation, learning disabilities and attention deficit disorder with hyperactivity and autism. Patients with TSC range from intellectually normal to severely retarded. The prevalence of learning disabilities ranges from 38% to 80%. Children with normal intelligence may have different specific neuropsychological deficits related to the strategic location of small, isolated cortical tubers, even when they are seizure-free. Studies of TSC children have identified rates of autism ranging from 17% to 61%. The cause of this association remains unknown. Several mechanisms may be implicated in the genesis of behavioral and cognitive phenotypes in TSC patients. Recently, several genome wide scans have suggested that a region on chromosome 16p13 shows a significant linkage to autism. New advances in molecular genetics and functional neuroimaging techniques will provide new insights in our understanding of the neurobiological bases of the behavioral and cognitive phenotypes associated with the disease.