Tuberous sclerosis complex is a rare genetic disorder. It’s a type of neurocutaneous syndrome, which are disorders that cause tumors (or lesions), seizures, brain development problems, and intellectual disabilities. The tumors — also known as hamartomatous lesions and tubers — are benign (noncancerous) and can form in the skin, bones, brain, and other organs.
TSC’s effects on different parts of the body vary greatly from person to person, in both severity and symptoms. TSC typically presents in early infancy. Seizures known as infantile spasms usually start during the first year. A person with TSC can develop other types of seizures over time.
TSC is a lifelong, chronic (ongoing) condition that currently has no cure. However, TSC is manageable. With early diagnosis and intervention, specialized health care, and frequent monitoring, people with TSC often live high-quality, productive lives and have a normal life expectancy.
According to the TSC Alliance, an estimated 1 million people are thought to have TSC worldwide, about 50,000 of whom live in the United States. Individuals with TSC often go undiagnosed until they’re adults.
In most cases, TSC is caused by a gene mutation that occurs on the TSC1 or TSC2 gene. The TSC1 gene is thought to control a protein called hamartin that suppresses tumor growth. The TSC2 gene controls a protein called tuberin that moderates cell growth. Scientists believe the TSC genes control the growth and size of cells and tumors. The TSC gene mutation prevents the proteins from functioning properly, which leads to rapid growth of the tubers and lesions. Although benign, they’re still potentially dangerous.
For about two-thirds of people with TSC, neither of their parents has TSC or the TSC gene mutations. This is called spontaneous or sporadic mutation. In approximately 33 percent 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.
In very rare cases, although neither parent has tuberous sclerosis, the TSC mutation can be passed on to a child through a process known as germline or gonadal mosaicism. When neither parent has TSC but one child does, any of their siblings have a 1 percent to 2 percent chance of having TSC as well.
Diagnosing tuberous sclerosis entails a thorough medical exam. The doctor will take a detailed medical history, conduct a TSC diagnostic assessment, and examine the skin — sometimes with a special ultraviolet light called a Wood’s lamp to help spot skin anomalies.
To diagnose tuberous sclerosis, doctors will look for 18 symptoms, divided into 11 major features and seven minor features.
A definite diagnosis of TSC must have two or more major features, or one major feature and two or more minor features of the disorder. A possible TSC diagnosis has either just one major feature or two or more minor features. In most cases, health care providers with experience diagnosing TSC are able to confirm a TSC diagnosis with the criteria alone.
Genetic tests can identify a TSC1 or TSC2 mutation. The presence of a gene mutation confirms a TSC diagnosis. The absence of a TSC mutation, however, does not rule out tuberous sclerosis. Approximately 15 percent of people diagnosed with TSC show no TSC1 or TSC2 mutations.
Once a doctor makes a definite TSC diagnosis, they may order some of the following tests. The tests described below are necessary to set baseline measurements and assess organ function and health:
Antiepileptic drugs (AEDs) can help control seizures. Some people have what’s called refractory — or drug-resistant — epilepsy. Refractory seizures don’t respond to medication. Uncontrolled seizures can lead to 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, also known as West syndrome, usually show up in the first year of life and affect nearly 35 percent of babies born with TSC. West syndrome often leads to pediatric epilepsies, such as Lennox-Gastaut syndrome (LGS) and other drug-resistant types of epilepsy. West syndrome and LGS can cause major cognitive and developmental delays, as well as intellectual deficits. They can also stall or regress (move backward) a baby’s developmental progress.
TSC causes different types of brain abnormalities, the impact and severity of which vary depending on their location, size, and growth rate. These brain abnormalities include:
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.
Among the major features are the following four skin symptoms:
Almost half of all people with TSC experience a form of renal (kidney) disease at some point in their life. Three common types of renal disorders associated with TSC are:
Approximately 50 percent of people with TSC have cardiac tumors called rhabdomyomas. Rhabdomyomas can grow smaller over time but occasionally lead to problems like cardiac arrhythmias and congestive heart failure.
As many as 50 percent of people with TSC also have eye involvement. It is important to routinely check the eyes and identify any lesions in the retina.
TSC is a lifelong condition that requires specialized care from pediatricians, neurologists, dermatologists, and cardiologists with TSC expertise. Tuberous sclerosis symptoms differ from person to person. Individual TSC treatment plans need to aggressively and promptly meet an individual’s unique, often-changing needs.
AEDs — also called antiseizure medications — are the primary treatment for recurrent seizures, and they successfully control epilepsy in about 70 percent of people who take them. TSC-related epilepsies are challenging to treat and even harder to treat long term. About half of TSC-related epilepsy cases are or become intractable (resistant to medication).
Two medications are approved by the U.S. Food and Drug Administration (FDA) to treat infantile spasms: Sabil (a formulation of vigabatrin) and H.P. Acthar Gel (a repository corticotropin). Both medications can have serious side effects.
Several efforts focus on repurposing already-approved drugs to treat TSC. Afinitor, a formulation of everolimus, is FDA-approved to treat SEGAs and advanced renal cell carcinoma. Everolimus also shows off-label promise as an antiepileptic drug. While not yet FDA-approved, rapamycin treatment has shown efficacy (works as expected) in shrinking SEGAs. Further studies exploring rapamycin’s effectiveness on other TSC-associated tumors are underway.
In 2020, the FDA approved Epidiolex (a formulation of cannabidiol, or CBD) for treating seizures associated with TSC in people ages 1 and older.
Depending on the type and region of a person’s seizure activity, epilepsy surgery may bring seizures under control. If the seizure focus can be targeted through precise brain imaging and an EEG, and if it’s in a part of the brain that won’t affect critical function or quality of life, surgery could reduce or eliminate epilepsy.
Vagus nerve stimulation (VNS) is a type of neuromodulation therapy approved by the FDA as an add-on treatment for refractory epilepsy in children 4 years old and up. VNS involves a small device, similar to a pacemaker, implanted in the chest. A person can also use a handheld magnet to deliver extra stimulus between the device’s regularly programmed pulses.
In small studies among people living with TSC, VNS was shown to be effective in decreasing seizure frequency in some individuals. Responsive neurostimulation is a similar type of neuromodulation therapy also used to treat epilepsy. This closed-loop brain stimulation system detects electrical activity in the brain and provides electrical stimulation to lessen seizure frequency. The FDA approved the Neuropace RNS System in 2013 for treating focal or partial seizures in adults 18 and up.
Dietary therapy can be used with 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.
The prognosis (outlook) for people living with TSC varies, as it depends on which organs are affected and the severity of symptoms. Symptoms may change, and new symptoms can arise over time.
A small-scale 2019 study noted a higher mortality rate among people with late-onset TSC, possibly due to kidney disease and illness related to dementia. Similarly, a small 2016 study of people with TSC found that kidney disease was a prominent cause of death and that people with learning disabilities may be at a higher risk of dying at an earlier age from complications of TSC.
With early diagnosis, lifelong monitoring of TSC symptoms, and a close partnership with a skilled treatment team, most people living with the condition have a normal life expectancy. Some children diagnosed with TSC may require lifelong care, and parents must learn to advocate for their changing health needs. Ongoing scientific research offers new discoveries and treatment possibilities, as well as hope for a cure.
MyEpilepsyTeam is an online community where more than 112,000 people with epilepsy and their loved ones share their experiences and advice. 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.