Tuberous sclerosis, tuberous sclerosis complex (TSC)

Overview  

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.