Tuberous sclerosis

Tuberous sclerosis complex (TSC) is an autosomal dominant genetically heterogeneous disease, characterised by the growth of multiple hamartomas in almost every organs and by a dramatic phenotypic variability. In most patients the first symptom is epilepsy in early infancy, never the less the clinical spectrum of TSC may vary from modest facial angiofibromas and hypopigmented skin spots in virtually asymptomatic individuals, to cardiac rhabdomyomas, multiple angiomyolipomas of the kidney, lymphangioleiomyomatosis of the lung, renal failure and mental retardation. Since the identification of the two TSC genes, TSCl on 9q34 and TSC2 on 16~13.3, our understanding of the molecular mechanisms of phenotypic variability has made significant progresses. This presentation will summarise the state-of-the-art of TSC, with special emphasis on genotype-phenotype correlation based on a large series of families referred to us for molecular diagnosis from over 50 Italian centres. Among patients with epilepsy of known type, the prevalence of infantile spasms was significantly higher in TSC2 than in the TSCl group. Regarding age-dependent signs, renal involvement appeared more severe in TSC2 than in TSCI: among subjects above 20 yrs of age, angiomyolipomas larger than 3 cm in size appeared to be more common in TSC2 patients (P<0.02). In conclusion, the data summarised above have significant impact in diagnosis, clinical management and genetic counselling of TSC patients and relatives at risk.