• Tuberous sclerosis complex (TSC) is a rare genetic disorder that causes benign (noncancerous) tumors and lesions to develop in multiple organ systems.
• The condition can affect various parts of the body, including the brain, skin, eyes, kidneys, and heart.
• There is no cure for TSC, but advances in treatment provide more options for better epilepsy control.

Tuberous sclerosis complex is a rare genetic disorder. It belongs to a group of conditions called neurocutaneous syndromes, which affect both the skin and nervous system. People with TSC develop hamartomas (benign tumors or lesions), seizures, developmental challenges, and intellectual disabilities. These tumors — also known as tubers — can form in the skin, brain, heart, lungs, eyes, and kidneys.

This article will explain what causes TSC, its symptoms, and how it’s treated. Some people call it “tuberous sclerosis” for short, but the full name is “tuberous sclerosis complex.” The full name is important because it shows that TSC affects many parts of the body and causes a wide range of symptoms.

TSC Throughout Life

TSC affects everyone differently. Symptoms can vary widely in severity, even among members of the same family. In most cases, TSC is diagnosed during infancy, often when a baby begins having seizures called infantile spasms in their first year of life. Over time, individuals with TSC may develop other types of seizures.

In most cases, tuberculosis sclerosis complex is caused by a gene mutation that occurs on the TSC1 or TSC2 gene.

Although TSC is a lifelong condition with no cure, it is manageable. Early diagnosis, access to specialists, and regular monitoring can help those with TSC lead productive lives. Many people have a normal life expectancy, though outcomes vary depending on factors like which organs are involved and whether complications develop.

About 1 million to 2 million people worldwide are living with TSC, including approximately 50,000 in the United States, according to the TSC Alliance, a nonprofit that supports people with TSC through research, advocacy, and education. However, some people with mild symptoms may not be diagnosed until adulthood.

What Causes Tuberous Sclerosis Complex?

TSC is caused by a gene mutation (change) on the TSC1 or TSC2 gene. These genes help control how cells grow and divide in the body. The TSC1 gene makes a protein called hamartin, and the TSC2 gene makes a protein called tuberin. Together, these proteins act as tumor suppressors, meaning they help stop cells from growing too fast or too large.

When one of these genes has a mutation, the proteins it produces don’t work properly. As a result, lesions can grow in different parts of the body. Even though the tumors aren’t cancerous, they can still cause problems by pressing on organs or interfering with their function.

In one-third of cases, the TSC mutation is inherited from a parent. TSC is an autosomal dominant disease, meaning just one parent needs to carry the gene mutation or have TSC to pass it on. Each child of someone with TSC (or one of the gene mutations) has a 50 percent chance of being born with TSC. For about two-thirds of people with TSC, neither parent has TSC or a known TSC gene mutation. This is called a spontaneous or sporadic mutation. In these cases, the chance of having another affected child is very low. However, in rare cases, a parent may have germline (or gonadal) mosaicism, meaning some of their reproductive cells carry the mutation. This condition can increase the chance of another child having TSC to about 2 percent.

How Is Tuberous Sclerosis Complex Diagnosed?

Diagnosing TSC involves a thorough medical exam. Doctors will take a detailed medical history, assess symptoms, and carefully examine the skin. Sometimes, they’ll use a special ultraviolet (UV) light called a Wood’s lamp to find skin lesions or other abnormalities that aren’t easily visible.

Diagnostic Criteria

To diagnose tuberous sclerosis, doctors will look for 18 symptoms, divided into 11 major features and seven minor features. A definite diagnosis of TSC requires two or more major features or one major feature plus two or more minor features. A possible diagnosis involves either one major feature or two or more minor features.

Hypomelanotic macules — light patches shaped like leaves — are among the first skin symptoms to appear in people with TSC.

Major Features

These are the more distinct and common signs of TSC, often involving:

• Skin changes, such as light patches, thickened skin, or facial growths
• Benign tumors, which may affect the brain, heart, kidneys, or eyes
• Lung and brain abnormalities visible on imaging

Minor Features

These are additional, less specific signs that may help confirm the diagnosis, including:

• Small skin changes, such as tiny white spots or subtle growths in the mouth
• Mild abnormalities in the eyes, bones, or kidneys

In most cases, doctors experienced in TSC can confirm a diagnosis based on these criteria alone.

Laboratory Tests

Genetic tests can detect changes in the TSC1 or TSC2 gene, which confirms TSC. However, these tests don’t always find a mutation. About 15 percent of people diagnosed with TSC have no detectable genetic change. In these cases, doctors rely on symptoms and medical imaging to make a diagnosis.

Imaging

Once a doctor makes a definite TSC diagnosis, they may order some of the following tests. The tests below are needed to measure baseline levels — the body’s normal readings — and check how well the organs are working:

• Computed tomography (CT) scans use rotating X-rays to detect tumors in the brain, lungs, and kidneys.
• MRI uses strong magnetic fields to detect tubers on the brain’s surface and identify subependymal giant cell astrocytomas (SEGAs) before the tumors obstruct normal functioning.
• An electroencephalogram (EEG) monitors brain waves for irregular activity through electrodes affixed to the scalp. This can help diagnose seizures.
• Echocardiography uses sound waves to study the heart’s functionality and movement. It can be used to evaluate the heart for benign tumors called rhabdomyomas.
• Electrocardiograms monitor and record the heart’s electrical impulses and may show abnormal electrical patterns.
• Renal ultrasonography uses sound waves and radio waves to take pictures of internal organs to identify and measure renal cysts (round, fluid-filled pouches that form on or in the kidneys).

Tuberous Sclerosis Complex and Epilepsy

Epilepsy is the most common neurological symptom of TSC. Around 80 percent of people living with TSC also have epilepsy. People with TSC can experience many types of seizures, including:

• Atonic seizures
• Absence seizures
• Focal (partial) seizures
• Infantile spasms
• Myoclonic seizures
• Tonic-clonic seizures

Antiseizure medications can help control seizures. Some people have what’s called refractory (or intractable) epilepsy. With this type, seizures don’t respond to medication. In some cases, there can be status epilepticus, a life-threatening condition.

Although epilepsy is usually one of the first signs of TSC, a person with the condition can develop seizures at any age, and seizures often change as a person grows older. Infantile spasms usually appear in the first year of life and affect nearly 50 percent of babies born with TSC. These seizures are a key feature of West syndrome, which can lead to other forms of epilepsy, including Lennox-Gastaut syndrome (LGS) in some cases. However, not all children with TSC and infantile spasms develop LGS. They can also stall or regress (move backward) a baby’s developmental progress.

Tuberous Sclerosis Complex and the Brain

TSC causes different types of brain abnormalities. The effects and severity depend on where they are, how big they are, and how fast they grow. These brain abnormalities include:

• Cortical tubers — These lesions develop and harden over time, usually on the brain’s surface.
• Subependymal nodules — These collections of cells are on the cerebral ventricle walls (areas of the brain that contain cerebrospinal fluid). Often, they harden by accumulating calcium.
• SEGAs — These benign tumors can become large enough to restrict the flow of cerebrospinal fluid in the brain and spine. As SEGAs grow, they can cause headaches and blurred vision, leading to fluid buildup around the brain.

TSC-associated neuropsychiatric disorders are the cognitive, developmental, behavioral, intellectual, and psychosocial complications often associated with tuberous sclerosis. Between 25 percent and 50 percent of people living with TSC may develop autism spectrum disorder. Learning disabilities affect at least 50 percent of people with TSC, and 30 percent have severe IQ impairments.

Children with TSC may be more likely to have emotional regulation or behavioral problems, which can make managing the condition even more challenging.

Tuberous Sclerosis Complex and the Skin

The following tuberous sclerosis skin pictures show major dermatological symptoms associated with TSC.

Angiofibromas — This is a type of facial rash that’s often characterized by small pink, red, reddish-brown, or dark brown spots that spread across the cheeks and nose in a butterfly-like pattern. They can also appear around the scalp, forehead, and nails.
Hypomelanotic macules — These are light patches shaped like leaves of an ash tree (and sometimes referred to as ash-leaf spots). They’re one of the first skin symptoms to appear in people with TSC.
Shagreen patches — These skin-colored lesions of irregular shape and thickness usually form on the lower back, but they also can develop on the buttocks or upper thighs.
Ungual fibromas — These smooth, hard lumps develop around and under fingernails and toenails, and they’re generally the same color as a person’s skin. They can also cause grooves and red or white streaks in nails.

Additionally, some people with TSC develop cephalic fibrous plaques, which are soft, skin-colored plaques that typically develop on the forehead or scalp.

Tuberous Sclerosis Complex and Major Organs

More than 80 percent of people with TSC experience renal (kidney) disease at some point in their life. The three common types of renal disorders associated with TSC are:

• Renal angiomyolipoma (or angiomyolipomas) — These benign tumors in the kidney don’t frequently cause symptoms but can grow or hemorrhage (bleed), which can be dangerous. More than 80 percent of people with TSC develop renal angiomyolipoma, in which weakened walls of blood vessels can burst. Around 20 percent of the time, the bleeding can be life-threatening. These tumors usually appear in late childhood or adolescence.
• Renal cysts — According to the TSC Alliance, around 50 percent of people with TSC will develop these “holes” in the kidney, which are often small and filled with benign fluid. The cysts can raise blood pressure and, if too many develop, cause kidney damage or failure.
• Renal cell carcinoma — Although very rare, this type of cancerous growth is also associated with TSC.

Approximately 50 percent of people with TSC have benign cardiac (heart) tumors called rhabdomyomas. Rhabdomyomas can grow smaller over time but occasionally lead to problems like cardiac arrhythmias and congestive heart failure.

Nearly 50 percent of people with TSC also have eye involvement, according to the TSC Alliance — though the number may be higher, given that not everyone with TSC receives thorough eye exams. It’s important to routinely check the eyes and identify any lesions in the retina.

How Are Seizures in Tuberous Sclerosis Complex Treated?

TSC is a lifelong condition that requires care from specialists such as pediatricians, neurologists, dermatologists, and cardiologists familiar with TSC. Because symptoms can be very different for each person, treatment plans should be tailored to their needs and adjusted quickly as needed.

Antiepileptic Drugs

Antiepileptic drugs (AEDs) — also called antiseizure medications — are the main treatment for recurrent seizures, and they successfully control epilepsy in about 70 percent of people. However, epilepsy caused by TSC can be particularly difficult to manage, and about half of TSC-related epilepsy cases become intractable (do not improve with medication).

Medications commonly used to treat seizures associated with TSC include:

• Steroid therapies — These are used for infantile spasms. Options include prednisone/prednisolone, which is given orally (by mouth), or adrenocorticotropic hormone (ACTH), given as a subcutaneous (into a muscle) injection. Side effects can include hypertension (high blood pressure), stomach irritation, infection, and unwanted weight gain.
• Vigabatrin (Sabril) — This is approved as a first-line treatment (the first and preferred option) for infantile spasms associated with TSC. Although it’s effective, it carries a risk of vision loss and requires monitoring​​.
• Everolimus (Afinitor) is used for treating certain types of seizures and tumors of the brain or kidney in people diagnosed with TSC.
• Cannabidiol (Epidiolex) — In 2020, the U.S. Food and Drug Administration (FDA) approved this drug for treating seizures associated with TSC in people ages 1 and older.
• Conventional antiseizure medications — These medications may be used if first-line treatments don’t work. They include lamotrigine, topiramate, levetiracetam, valproate, and others.

A drug called sirolimus (Rapamune and Rapamycin) is FDA-approved for lymphangioleiomyomatosis (LAM), a lung disease associated with tuberous sclerosis. This drug has also been shown to shrink SEGAs. Used as a gel (Hyftor), it can help treat facial angiofibroma.

Devices and Surgery

For some individuals with TSC, surgical or device-based treatments may help control seizures when medications are not effective.

Epilepsy Surgery

For individuals with TSC and drug-resistant epilepsy, epilepsy surgery may help reduce or eliminate seizures, particularly when medications are not effective. Surgery is most effective when the seizure focus (the part of the brain where seizures begin) can be identified using brain imaging and EEG. A healthcare provider may consider surgery when removing the seizure focus won’t harm critical functions, such as speech, memory, or movement.

There are two main types of epilepsy surgery:

• Surgical resection is a traditional surgery where a part of the skull is opened, and the seizure focus is physically removed from the brain.
• Laser or thermal ablation therapy is a less invasive procedure. It uses heat from an electrode to destroy the small part of the brain, causing the seizures. The electrode is inserted through a small hole in the skull, making recovery quicker compared to resection.

Research shows that epilepsy surgery is often more effective when performed early, so it’s commonly recommended for children with TSC. However, adults with TSC have also undergone surgery successfully.

Vagus Nerve Stimulation

Vagus nerve stimulation (VNS) is a type of neuromodulation therapy, which uses electrical signals to change nerve activity. Approved by the FDA for children 4 years and older with refractory epilepsy (seizures that don’t respond to medication), VNS involves a small device, similar to a pacemaker, implanted in the chest. A handheld magnet can also be used to deliver extra stimulation between the device’s programmed pulses during a seizure.

Research has shown that VNS is generally safe and effective for TSC-related epilepsy. In one small-scale study, 70.6 percent of participants experienced at least a 50 percent reduction in seizure frequency, and some became completely seizure-free after treatment. Additionally, VNS may improve mood in people with TSC-related epilepsy, although further research is needed to confirm this benefit​.

Responsive Neurostimulation

Responsive neurostimulation (RNS) is another neuromodulation therapy used to treat epilepsy. Like VNS devices, RNS devices are implanted. They detect abnormal brain activity in real time and deliver targeted stimulation only when a seizure is about to occur.

The Neuropace RNS System, approved by the FDA in 2014, is designed for adults 18 and older with focal (partial) seizures. This system works by detecting abnormal electrical activity in the brain and providing targeted electrical stimulation to reduce seizure frequency. In small-scale testing, people with TSC who used this treatment saw at least a 50 percent reduction in seizure frequency.

Dietary Therapy

Dietary therapy can be used alongside AEDs to help control seizures. A ketogenic diet is a strict regimen of high-fat and low-carbohydrate foods. It has proved effective in helping control some epilepsy conditions — including TSC — in some individuals. The modified Atkins diet is similar to the ketogenic diet but includes more carbohydrates and greater flexibility.

What Is the Tuberous Sclerosis Life Expectancy?

The prognosis (outlook) and life expectancy for people with TSC vary depending on which organs are affected and how severe the symptoms are. Most individuals with TSC have a normal lifespan. However, problems in organs like the brain and kidneys can develop and may cause serious health issues or even death if not treated. Regular checkups with doctors are important to help prevent these risks.

Research highlights certain risks:

• A 2019 study linked late-onset TSC to a higher mortality rate, possibly due to kidney disease and dementia-related illnesses.
• A 2016 study found that kidney disease is a major cause of death in TSC, with individuals who have learning disabilities at higher risk for earlier death.

With early diagnosis and consistent care, most people with TSC can live a normal life. Lifelong care and advocacy are important, especially for children diagnosed with TSC, as their health needs may change over time. Advances in research continue to improve treatments and offer hope for the future.

Meet Your Team

On MyEpilepsyTeam, the social network for people with epilepsy and their loved ones, more than 124,000 members come together to ask questions, give advice, and share their stories with others who understand life with epilepsy. Several members of MyEpilepsyTeam or their children have been diagnosed with tuberous sclerosis complex.

Have you or a loved one been diagnosed with TSC? Do you have questions about symptoms or treatments? Comment below or post on your Activities page.