Tuberous Sclerosis Complex (TSC)

Tuberous sclerosis complex (TSC), also known as tuberous sclerosis, is a rare genetic disease that causes non-cancerous (benign) tumors to grow in the brain and several areas of the body, including the spinal cord, nerves, eyes, lung, heart, kidneys, and skin.

Many people with TSC show signs of the disorder as early as the first year of life, while the signs and symptoms may take years to develop in others.  All individuals with TSC are at risk for life-threatening conditions related to the brain tumors, kidney lesions, or lung lesions.

1. Cortical tubers, for which the disease is named, generally form on the surface of the brain but may also appear in the deep areas of the brain
    
2. Subependymal nodules (SEN), which form in the walls of the ventricles (fluid-filled cavities of the brain)
    
3. Subependymal giant-cell astrocytomas (SEGA), which develop from SEN and grow to potentially block the flow of fluid within the brain, which causes a buildup of fluid and pressure that can lead to headaches and blurred vision

Most people with TSC are affected by seizures at some time in their life. While some kinds of seizures caused by TSC result in obvious convulsive movements, others alter awareness, behavior, or postural tone without convulsions.

Developmental delay occurs in about one-half to two-thirds of people with TSC. Delays range from mild learning disabilities to severe impairment of cognitive abilities.

Aggressive behavior, sudden rage, attention deficit hyperactivity disorder, acting out, obsessive-compulsive disorder, and repetitive, destructive, or self-harming behavior occur in children with TSC and can be difficult to manage.

There is a strong relationship between autism spectrum disorder and TSC. Many children with TSC develop autism spectrum disorder.

Apart from brain tumors other types of tumors can form in the hearts (rhabdomyomas) and eyes (phakomas) of infants and young children with TSC. Tumors and cysts may also form in other areas of the body, including the liver, lung, and pancreas. 

• Hypomelanic macules ("ash leaf spots"), which are white or lighter patches of skin that may appear anywhere on the body and are caused by a lack of skin pigment or melanin—the substance that gives skin its color.
   
• Facial angiofibromas (also known as adenoma sebaceum) are reddish spots or bumps which appear on the face (sometimes resembling acne) and consist of blood vessels and fibrous tissue.
   
• Forehead plaques are raised, discolored areas on the forehead which are common and unique to TSC and may help doctors diagnose the disorder.
   
• Shagreen patches are areas of thick leathery, pebbly skin, usually found on the lower back or nape of the neck.
   
• Ungual or subungual fibromas are small fleshy tumors that grow around and under the toenails or fingernails and may need to be surgically removed if they enlarge or cause bleeding. These usually appear later in life, ages 20-50.

Other skin features that are not unique to individuals with TSC, including molluscum fibrosum or skin tags (typically occuring across the back of the neck and shoulders), café au lait spots or flat brown marks and poliosis (a tuft or patch of white hair that may appear on the scalp or eyelids)

Cysts and Angiomyolipomas are benign growths of fatty tissue and muscle cells) occur in an estimated 70 to 80 percent of individuals with TSC. They usually occur between ages 15 and 30.

Cysts are usually small, appear in limited numbers, and most often cause no serious problems. A very small percent of individuals with TSC develop large numbers of cysts during childhood, which may lead to hypertension, proteinuria and kidney failure.

Angiomyolipomas are the most common kidney lesions in TSC and can be found in people without TSC. Angiomyolipomas caused by TSC are usually found in both kidneys and in most cases do not produce symptoms. However, they can sometimes grow so large that they cause pain or kidney failure. Bleeding from angiomyolipomas may also occur, causing both pain and weakness and, in some instances, severe blood loss resulting in profound anemia and a life-threatening drop in blood pressure, warranting urgent medical attention.
 

Other rare kidney problems include renal cell carcinoma, developing from an angiomyolipoma, and oncocytomas, benign tumors unique to individuals with TSC.

Treatment plans for TSC should be individualized based on the specific symptoms and complications experienced by each patient. Regular follow-up with a team of specialists, including neurologists, dermatologists, nephrologists, and other relevant specialists, is essential to provide comprehensive care and monitor the progression of the disease. Early intervention and ongoing management can help improve the overall quality of life for individuals with TSC. Treatment is tailored to address specific organ involvement and complications.

Mammalian Target of Rapamycin (mTOR) Inhibitors: 

Drugs like everolimus and sirolimus, which are mTOR inhibitors, have been approved for the treatment of specific TSC-related complications, such as kidney angiomyolipomas (AMLs) and brain subependymal giant cell astrocytomas (SEGA). These medications can help shrink or stabilize tumors.

Seizure Management: 

TSC is often associated with epilepsy, and seizure management is a crucial aspect of treatment. Medications and, in some cases, epilepsy surgery or vagus nerve stimulation (VNS) may be recommended.

Behavioral and Developmental Support: 

For children with TSC who experience developmental delays or behavioral issues, early intervention services, including speech therapy, occupational therapy, and behavioral therapy, can be beneficial.

Dermatological Treatment:

Skin lesions, including facial angiofibromas and hypomelanotic macules, can be treated with laser therapy or topical medications.

Surgery:  

Regular monitoring of kidney function and imaging to assess the size and growth of kidney tumors (angiomyolipomas) is important. In some cases, embolization or surgery may be necessary to manage large or symptomatic AMLs.

Cardiac Evaluations:

Regular cardiac evaluations may be recommended to monitor for the presence of cardiac rhabdomyomas or other cardiac issues.

Pulmonary Function Testing:

Individuals with TSC may develop lung involvement, including lymphangioleiomyomatosis (LAM). Pulmonary function testing may be necessary to monitor lung function.

Ophthalmology Evaluation:

TSC can affect the eyes, and regular ophthalmologic evaluations may be needed to check for issues such as retinal hamartomas.

Genetic Counseling:

Individuals with TSC and their families may benefit from genetic counseling to understand the genetic basis of the condition and the potential risk of passing it on to future generations.

Psychosocial Support: 

Living with a chronic condition like TSC can be challenging, and individuals and families may benefit from counseling and support groups to address the emotional and psychosocial aspects of the condition.