Tuberous Sclerosis

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General Information

Tuberous Sclerosis

Who is at risk?

Tuberous sclerosis complex (TSC) is a genetic disorder that can affect both children and adults. Recent incident rates have been estimated between 1/6,000 to 1/10,000 live births and the prevalence is estimated around 1 in 20,000. While Tuberous Sclerosis is an autosomal dominant disorder, two-thirds of patients have sporadic mutations. 


The TSC1 (hamartin) gene on chromosome 9 and the TSC2 (tuberin) gene on chromosome 16 have been implicated in Tuberous Sclerosis. In familial Tuberous Sclerosis cases, mutations in TSC1 and TSC2 genes are found nearly equally. However, in sporadic cases, TSC2 gene mutations are found much more frequently. TSC2 mutations have been implicated in nearly 80% of sporadic cases. Mutations are found in 75-90% of patients who undergo molecular testing of the TSC1 and TSC2 genes; larger deletions are seen more commonly in the TSC2 genes.


Tuberous Sclerosis Complex is a multisystem disorder and many organ systems can be involved. The most commonly involved organ systems include the skin and nervous system with reports of up to 90% of patients with Tuberous Sclerosis having involvement in these organ systems. Patients with Tuberous Sclerosis have an increased risk of invasive malignancies which are typically found in the kidneys, brain and soft tissues. While a classic symptomatic triad includes seizures, mental retardation and facial adenoma sabaceum, other common manifestations by organ systems are listed below:

  • Neurologic: Subependymal giant cell tumors, glioneuronal hamartomas, white matter heterotopia, epilepsy, cognitive impairment, behavioral problems and autism
  • Dermatologic: Shagreen patches, Ash-leaf spots, angiofibromas and distinctive brown fibrous patches on the forehead
  • Pulmonary: cystic lung disease – identical to lymphangioleiomyomatosis (LAM)
  • Cardiovascular: rhabdomyoma
  • Renal: Angiomyolipomas
  • Ophthalmic: Retinal hamartomas, angiofibromas of the eyelids and refractive errors

Patients with lung involvement usually do not present with the classic symptomatic triad. The proportion of females with lung manifestation of Tuberous Sclerosis has been estimated at 30-50%, while an estimate of lung involvement in men is around 10%. Manifestations of lung involvement include dyspnea, spontaneous pneumothorax and hemoptysis.


The diagnostic criteria for Tuberous Sclerosis were updated by the International Tuberous Sclerosis Complex Consensus group in 2012. The diagnosis of Tuberous Sclerosis can be made both on genetic or clinical grounds. This indicates that a pathogenic gene mutation found on TSC1 or TSC2 is sufficient to make a diagnosis regardless of the clinical features. The clinical features are classified into major and minor features. Based on these features, there are two possible designations: “definite” and “possible” diagnosis. A “definite” diagnosis requires at least two major features or one major feature plus two or more minor features. A “probable” diagnosis requires one major or two or more minor features.

Prognosis and Management

Tuberous Sclerosis is a variable disease. Depending on the involvement, patients can have a normal life expectancy. Tuberous Sclerosis is typically a progressive disorder with features that are more prevalent at different stages of life. For example, during childhood, the dermatologic features typically become more noticeable. In adulthood, features such as angiolipomas and LAM are more prevalent.  

Previously, management of Tuberous Sclerosis was centered on symptomatic control such as managing seizures in early childhood to prevent developmental delay. However, advances in the understanding of the role of cell signaling mediated by the mechanistic target of rapamycin (mTOR) has led to medical therapies. Everolimus is now being used in patients with Tuberous Sclerosis. Another mTOR inhibitor, sirolimus, has been studies in lung involvement, particularly LAM.


Four Facts About Tuberous Sclerosis

  1. Tuberous sclerosis complex (TSC) is a genetic disease that causes non-cancerous tumors to form in various vital organs, primarily in the brain, eyes, heart, kidneys, skin and lungs.

  2. TSC affects more than 1 million people worldwide and approximately 50,000 people in the United States. At least two children born each day in the United States will have tuberous sclerosis complex.

  3. Approximately 40% of women with TSC will develop LAM, a progressive lung disease that usually strikes women during their childbearing years.

  4. Most people with TSC will live a normal life span. However, complications in some organs such as the lungs, kidneys and brain can lead to severe difficulties and even death if left untreated.