BACKGROUND AND DESIGN: Tuberous sclerosis (TS) is a genetic disease with 
prominent cutaneous and brain involvement whose clinical and molecular genetics 
are reviewed.
OBSERVATIONS: Tuberous sclerosis is a systemic disorder (incidence one in 
10,000) characterized by benign growths (hamartias and hamartomas) in multiple 
organ systems. Involvement of the brain can result in persistent seizures and 
mental retardation; skin involvement includes facial angiofibromas, subungual 
fibromas, hypomelanotic macules, forehead fibrous plaques, and Shagreen's 
patches. Approximately 60% of TS occurs as apparent sporadic cases. In families, 
it has autosomal dominant inheritance with high penetrance (approximately 95%), 
with careful clinical and radiologic evaluation. Genetic linkage analysis 
indicates that about half of all TS families show linkage to chromosome 9q34, 
and about half to chromosome 16p13. There are no distinguishing features in the 
two groups of families showing linkage to the two genomic regions, nor strong 
evidence for a third causative gene. Positional cloning efforts for both 
chromosomal regions have limited the region containing the gene to about 1 to 2 
million bases.
CONCLUSIONS: Identification of the two TS genes should illuminate the 
pathogenesis of TS and provide opportunities for genetic counseling, prenatal 
diagnosis, and therapeutic intervention.