Tuberous sclerosis complex

An autosomal-dominant, neurocutaneous, multi-system disorder characterised by cellular hyperplasia, tissue dysplasia, and multiple organ hamartomas.

The primary recognised neurocutaneous features include dental pits, hypopigmented macules (ash leaf spots), facial angiofibromas, and ungual fibromas.

The most often identified clinical presentations are epilepsy (infantile spasms), autism and cognitive impairment, and neonatal cardiac rhabdomyomas.

Cardiac rhabdomyomas regress in early childhood and are generally asymptomatic, whereas renal angiomyolipomas and giant cell astrocytomas progress in adolescence and adulthood. The renal complications are second only to the central nervous system complications as a cause of significant morbidity.

Lymphangioleiomyomatosis of the lung associated with tuberous sclerosis is unique in that it is identified in females only and arises from metastases from renal angiomyolipomas.

Tuberous sclerosis complex (TSC) is an autosomal-dominant, neurocutaneous, multi-system disorder characterised by cellular hyperplasia, tissue dysplasia, and multiple organ hamartomas.[1]Gomez M, Sampson J, Whittemore V, eds. The tuberous sclerosis complex. Oxford: Oxford University Press; 1999.[2]Hyman MH, Whittemore VH. National Institutes of Health consensus conference: tuberous sclerosis complex. Arch Neurol. 2000 May;57(5):662-5. http://www.ncbi.nlm.nih.gov/pubmed/10815131?tool=bestpractice.com The disease has 2 genetic loci: TSC1, found on chromosome 9q34; and TSC2, found on chromosome 16p13.[2]Hyman MH, Whittemore VH. National Institutes of Health consensus conference: tuberous sclerosis complex. Arch Neurol. 2000 May;57(5):662-5. http://www.ncbi.nlm.nih.gov/pubmed/10815131?tool=bestpractice.com [3]European Chromosome 16 Tuberous Sclerosis Consortium. Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell. 1993;75:1305-1315. http://www.ncbi.nlm.nih.gov/pubmed/8269512?tool=bestpractice.com [4]van Slegtenhorst M, de Hoogt R, Hermans C, et al. Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science. 1997;277:805-808. http://www.ncbi.nlm.nih.gov/pubmed/9242607?tool=bestpractice.com The clinical phenotype can result from a mutation in either of these genes.[5]Dabora SL, Jozwiak S, Franz DN, et al. Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared to TSC1, disease in multiple organs. Am J Hum Genet. 2001;68:64-80. http://www.cell.com/ajhg/fulltext/S0002-9297(07)62472-0 http://www.ncbi.nlm.nih.gov/pubmed/11112665?tool=bestpractice.com [6]Cheadle J, Reeve M, Samson J, et al. Molecular genetic advances in tuberous sclerosis. Hum Genet. 2000;62:345-357. http://www.ncbi.nlm.nih.gov/pubmed/11030407?tool=bestpractice.com [7]Au KS, Williams AT, Roach ES, et al. Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States. Genet Med. 2007;9:88-100. http://www.ncbi.nlm.nih.gov/pubmed/17304050?tool=bestpractice.com