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Tuberous sclerosis complex: Genetics, clinical features, and diagnosis

James Owens, MD, PhD
John B Bodensteiner, MD
Section Editors
Marc C Patterson, MD, FRACP
Helen V Firth, DM, FRCP, DCH
Alberto S Pappo, MD
Deputy Editor
John F Dashe, MD, PhD


Tuberous sclerosis complex (TSC) is an inherited neurocutaneous disorder that is characterized by pleomorphic features involving many organ systems, including multiple benign hamartomas of the brain, eyes, heart, lung, liver, kidney, and skin [1-3]. The expression of the disease varies substantially. The diagnosis of TSC is made clinically.

The genetics, clinical features, and diagnosis of TSC will be reviewed here. Other aspects of TSC are discussed elsewhere. (See "Tuberous sclerosis complex: Management" and "Renal manifestations of tuberous sclerosis complex" and "Pulmonary involvement in tuberous sclerosis complex".)


Tuberous sclerosis complex is an autosomal dominant genetic disorder with an incidence of approximately 1 in 5000 to 10,000 live births [3-7]. It is caused by a mutation in either the TSC1 gene or the TSC2 gene. De novo mutations account for approximately 80 percent of TSC cases, with TSC2 mutations being approximately four times as common as TSC1 mutations among de novo cases, while the prevalence of TSC1 and TSC2 mutations is approximately equal among familial TSC cases [8].

There are several different explanations for the apparently nonfamilial cases. Most often, such cases result from a de novo mutation in the egg or sperm prior to fertilization. In addition, the parent may be a somatic mosaic where a subset of somatic and germ cells carry the mutation, or a gonadal mosaic in which mosaicism is confined to the parental germline [9-11]. In germline mosaicism, there may be more than one egg or sperm that contains the mutation, which can result in more than one sibling affected with the disease (ie, there is an appreciable recurrence risk). Finally, in a child with no affected parents or siblings, TSC may be the result of somatic mosaicism where the mutation occurred during the child's development and after fertilization. [9]. Once a "de novo" germline mutation occurs in an individual, their offspring may inherit TSC, which then appears as a familial trait in subsequent generations. (See 'Genetic testing' below.)

TSC is highly variable in its expression, that is, in the range of phenotypic changes such as age of onset, severity of disease, and different signs and symptoms that result from a specific genotype. (See "Basic principles of genetic disease".)


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Literature review current through: Sep 2016. | This topic last updated: Jun 27, 2016.
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