Tuberous sclerosis, tuberous sclerosis complex (TSC)
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Tuberous sclerosis complex (TSC) is a rare genetic disease characterized by the development of noncancerous tumors in multiple body parts. These benign growths consist of abnormal cell and tissue accumulations that don’t spread like cancer. The symptoms of TSC vary significantly, ranging from very mild, where individuals may not notice any effects and lead normal lives, to severe cases that can result in significant health complications.
The condition is often identified during infancy or childhood, but its symptoms can be so subtle that some people don’t receive a diagnosis until adulthood, if at all. TSC progresses at a variable rate; some symptoms may appear early on, while others may take years to develop. Regular medical monitoring is essential for managing the condition throughout an individual’s life.
Although there is no cure for tuberous sclerosis, various treatments are available to manage its symptoms and mitigate its impact. The progression of TSC is unpredictable, and treatment strategies must be customized to meet the unique needs of each patient, helping them maintain the best possible quality of life.
Symptoms
The severity of tuberous sclerosis symptoms can vary according to the size and location of the growths. Generally, it can cause a wide range of symptoms because it affects different parts of the body.
Symptoms include:
- Brain–related issues: Two common types of brain–related tumors in TSC are subependymal giant cell astrocytomas (SEGAs) and cortical tubers. These brain–related issues can cause additional symptoms, such as seizures, developmental delays, mental disabilities, and conditions like autism spectrum disorder or attention–deficit/hyperactivity disorder (ADHD). However, not everyone with TSC experiences these symptoms, and some people with TSC may have seizures but no mental disabilities.
- Skin changes: Skin–related symptoms are often among the first signs of TSC. These skin symptoms can help diagnose TSC and can vary in visibility and severity. These can include lighter patches called “ash leaf spots,” shagreen patches or thickened fibrous tissue with a bumpy texture, and tiny soft bumps under or around the nails. Growths that resemble acne can form on the face, usually starting in childhood. On the forehead, the skin might also develop raised, discolored spots.
- Mouth problems: On the tongue, inside the cheeks, and on the gums, tiny growths may show up. Fibromas or pits can develop in the teeth due to a lack of enamel, which can lead to irritation, bleeding, and cavities.
- Behavior issues: This may include having trouble with social skills and managing emotions, being overly active, and hurting oneself or others.
- Kidney problems: Kidney cysts and growths can affect kidney function, leading to symptoms like back or side pain, blood in the urine, or kidney stones. In severe cases, these growths could cause kidney failure or even kidney cancer.
- Cardiac issues: Cardiac rhabdomyomas are growths in the heart that pose the most risk to infants, as they can interfere with blood flow, though these complications become less likely with age.
- Lung problems: Females are more likely than males to get lung tumors. Lung growths can lead to coughing or breathing difficulties, particularly during vigorous exertion or exercise.
- Eye problems: Growths in the eyes, specifically on the retinas or optic nerves, might impact vision but are not common. The growths might show up as white patches.
If any of the signs and symptoms are observed, consult a healthcare provider for proper diagnosis and treatment. Tuberous sclerosis can show symptoms at birth, during childhood, or later in adulthood. People with TSC also requires regular monitoring of their condition to catch any changes early, which can prevent serious complications.
In cases of seizures which lasts more than five minutes or when there are multiple seizures without recovery time in between, seek medical attention immediately as this can be life–threatening.
Causes
Tuberous sclerosis arises from genetic mutations impacting DNA regulation. Typically, the body employs tumor–suppressing proteins to regulate cell reproduction and size. When these proteins malfunction, cells can proliferate excessively and enlarge, resulting in tumor development. The mutations responsible for TSC occur within either the TSC1 or TSC2 genes.
Risk factors
Tuberous sclerosis is a genetic disorder that can arise from a random mutation in the TSC1 or TSC2 genes during cell division, which occurs in about two–thirds of cases, often without a family history of the condition. Alternatively, it can be inherited from a parent who carries a genetic mutation, accounting for about one–third of cases. Individuals with tuberous sclerosis have a 50% chance of passing the mutated gene and associated disorder to their biological children. The severity of the disorder can vary significantly, even within the same family, meaning a parent with tuberous sclerosis could have a child with either a milder or more severe form of the condition.
Diagnosis
The diagnosis of tuberous sclerosis complex requires discussing one’s symptoms and family history, conducting a physical examination, and ordering several tests.
Major features include three or more ash leaf spots, multiple facial fibromas, a Shagreen patch, fibromas on fingernails or toenails, specific types of brain or heart growths, and benign tumors in the lungs, kidneys, or lymph nodes. Minor features are smaller signs such as confetti–like skin lesions, pits in teeth enamel, multiple growths in the mouth or on retinas, kidney cysts, and benign growths in other organs.
Tests that may be ordered include:
- Physical examination: During a physical examination, healthcare providers usually look for growths, or noncancerous tumors, or at a range of signs and symptoms that are classified into major and minor features. A definite TSC diagnosis requires at least two major features.
- Eye examination: The retina and other internal components of the eye are examined using a light source and magnifying glass.
- Dental examination: This may require X–rays of the jaws and teeth to thoroughly examine the interior of the mouth and the teeth.
- Electroencephalogram (EEG): If one is experiencing brain–related symptoms, like seizures, this test may be required. An EEG can assist in identifying the cause of seizures by recording electrical activity in the brain.
- Imaging tests: Magnetic resonance imaging (MRI), computed tomography (CT) scan, and ultrasound are used to find abnormal growths or changes in the body. Ultrasound, also known as sonography, uses high–frequency sound waves to create images of organs like the liver, heart, or kidneys. A CT scan uses X–rays to make cross–sectional or 3D images of the brain or other body parts. While an MRI creates detailed pictures of the brain or other areas using magnetic fields and radio waves.
- Cardiac tests: An electrocardiogram, also known as an ECG or EKG, records the electrical signals from the heart to see if there are any irregularities in the heartbeat or rhythm. While an echocardiogram uses sound waves to create images of the heart, showing how well it is working and if there is any damage.
- Assessment of developmental or mental health: This evaluation helps identify issues like behavioral or emotional disorders in children, developmental delays, learning or functioning difficulties, and educational or social challenges.
- Genetic testing: For individuals with TSC, genetic counseling before starting a family provides insights into their chances of passing on the condition.
Generally, genetic testing is crucial for detecting TSC as 75% to 95% of cases have a mutation in the TSC1 or TSC2 gene. This can be useful when there is no family history of the condition. If a child is diagnosed with TSC, it can be beneficial for the parents to consider getting tested too, as this can reveal whether the condition has a genetic link.
Treatment
While tuberous sclerosis currently lacks a cure, treatment options are available and tailored based on the specific symptoms experienced by individuals.
Common treatments include:
- Medications: Various medications can help manage symptoms of TSC depending on one’s symptoms, health history, and personal needs. Skin growths similar to acne may be treated with sirolimus, a medication, in the form of topical ointment. When surgical excision is not an option for some kinds of brain and kidney growths, a medication known as everolimus may be utilized.
Patients may receive anti–seizure medication as part of their treatment plan. Additionally, other medications might be prescribed to address behavioral concerns, irregular heartbeat, or other associated symptoms.
- Surgery: Surgery might be needed to remove growths that are affecting different organs or body systems. Skin growths may appear better after surgical techniques like dermabrasion or laser treatment. Surgery can occasionally be performed to treat seizures brought on by brain tumors that are resistant to medication.
- Therapy: Children’s capacity to organize everyday activities and chores might be enhanced by certain therapies. Therapies include early intervention programs like speech, physical, or occupational therapy.
- Educational and support services: For managing behavior, social, or emotional issues, specialized healthcare providers can offer guidance. Early intervention and special needs services can support children with developmental delays and behavior issues to adapt to school and reach their full potential. Social, vocational, and rehabilitation services might continue to support them throughout their lives.
- Continued monitoring: Maintaining a consistent schedule for regular check–ups and tests is crucial for early detection and management of potential issues, thus reducing the risk of complications in the future. Given that tuberous sclerosis is a lifelong condition with symptoms that may manifest over years, ongoing monitoring is essential.
