What is Tuberous Sclerosis (TSC)?

Tuberous Sclerosis Complex (also commonly referred to as tuberous sclerosis or TS) is a genetic condition that affects many organs and can cause tumors in the skin, kidney, brain, heart, eyes, lungs and other organs. The severity of TSC can range from mild, such as skin abnormalities, to severe, such as seizures, mental retardation or renal failure. TSC affects approximately 50,000 people in the United States and one million worldwide, with an estimated incidence of 1 in 6,000 live births.

What are the symptoms of TSC?

The most common symptoms of TSC are seizures and developmental delay as well as benign tumors and lesions which can affect virtually every organ system of the body including the brain, kidneys, heart, lungs, eyes, skin, and other organs. In many instances, symptoms of TSC will be apparent in the first six months of life.

Brain and Neurological Function:

In 95% of individuals with TSC, the brain is somehow affected. This usually takes the form of cortical tubers, subependymal nodules and subependymal giant cell astrocytomas, which can be detected by brain imaging.

Epilepsy is by far the most common medical condition in TSC, occurring in 80-90% of individuals. In about one third of individuals with TSC, epilepsy starts out as infantile spasms. Peak onset occurs at about 4-6 months of age.

Individuals with TSC have an increased risk of having neurodevelopmental and behavioral impairment. Although approximately 50% of individuals with TSC have normal intelligence, developmental delay and learning disabilities are commonly found in children with TSC. Additionally, up to 60% of individuals with TSC can develop autism.

Skin:

Skin lesions, including those found on the face, body and nails, are found in almost all individuals with TSC. The earliest sign may be white skin patches (hypomelanotic macules), which are best seen under ultraviolet light. As a child grows older, a characteristic facial rash across the nose and cheeks may appear.

Heart:

Cardiac (heart) involvement is common in TSC and is found in up to two thirds of individuals. Benign heart tumors (cardiac rhabdomyomas) are often an early sign of TSC. Fortunately, these tumors often regress spontaneously, shrinking or completely disappearing with time.

Kidney:

Kidney lesions occur in over half of all children at the time of initial evaluation. Benign renal lesions, which account for 75% of abnormalities, are made up of vascular tissue, smooth muscle, and fat. They usually grow very slowly and may not be problematic until young adulthood. Larger kidney lesions can cause symptoms and may require intervention.

What causes TSC?

TSC is caused by a mutation (gene change) in one of two genes: TSC1 and TSC2. Genetic testing for TSC at this time is able to detect mutations in the TSC1 or TSC2 genes in approximately 80% of individuals. For the other 20% of individuals without an identifiable mutation, researchers are studying ways to accurately find mutations in these two known genes and look for additional genes that may be involved.

How is TSC inherited?

In general, one third of individuals with TSC inherit the genetic condition from a parent. Two thirds of all cases are sporadic, or occur for the first time in a family.

TSC is inherited as an autosomal dominant genetic condition. This means that a mutation in only one copy of the gene causes the condition. Individuals with TSC have a 50% chance of passing their condition to each of their children.

How is TSC diagnosed?

Clinical diagnosis of TSC is based on a careful physician exam in combination with imaging of the brain, heart and kidneys. The physician will carefully examine the skin for the wide variety of skin lesions, often using an ultraviolet light called a Wood’s lamp which may be useful for finding skin features that can be hard to see on infants or individuals with pale skin.

There is no single clinical feature absolutely specific to the condition. In addition, many features of TSC, such as seizures and developmental delay, are seen in individuals without TSC. Therefore, a constellation of features is necessary for the diagnosis, and an increasing number of features make the clinical suspicion of TSC more likely.

Recently, genetic testing for TSC has become more readily available, and a positive genetic test can be considered diagnostic.

What is the prognosis of TSC?

The prognosis of individuals with TSC varies from individual to individual. The severity of the complications determines the long term outlook, and symptoms can range from mild to extremely severe. Most individuals who are mildly affected with TSC and are under an experienced physician’s care can expect to live active and productive lives with normal life expectancy.

What is the treatment of TSC?

While, unfortunately, there is no cure for TSC yet, effective treatments are available for a variety of the symptoms. Drugs to prevent seizures are accessible to individuals and surgery can often correct skin abnormalities. Surgery to remove tumors can help to preserve the function of affected organs. For other symptoms of TSC, such as developmental delay, services such as early intervention, special education and other therapies are often effective in moderating symptoms.

Advancements in research show great promise in developing new and improved treatment options. There are currently several clinical trials ongoing for symptoms of tuberous sclerosis.  Please click here for ongoing clinical trials in our TSC clinic.