Tuberous sclerosis complex
Tuberous sclerosis complex is a genetic disorder characterized by the growth of numerous noncancerous (benign) tumors in many parts of the body, often leading to significant health and developmental problems.
Overview
Tuberous sclerosis complex is a genetic disorder characterized by the growth of numerous noncancerous (benign) tumors in many parts of the body. These tumors can occur in the brain, kidneys, heart, skin, and other organs, in some cases leading to significant health problems. The condition also causes developmental problems, and its signs and symptoms vary from person to person.
Tuberous sclerosis complex often affects the brain, with some affected individuals having benign growths in the outer surface of the brain (cerebral cortex) known as cortical tubers.
Associated Neuropsychiatric Disorders (TAND)
Individuals with tuberous sclerosis complex often develop a pattern of behaviors called TSC-associated neuropsychiatric disorders (TAND). These disorders include:
- Hyperactivity
- Aggression
- Psychiatric conditions
- Intellectual disability
- Problems with communication and social interaction (autism spectrum disorder)
Additionally, individuals with tuberous sclerosis complex may have attention-deficit/hyperactivity disorder (ADHD) or seizures.
Organ Manifestations
- Kidney tumors are common and can cause severe problems with function, potentially being life-threatening.
- Tumors can develop in the heart (cardiac rhabdomyoma) and the light-sensitive tissue at the back of the eye.
- Some women develop lymphangioleiomyomatosis (LAM), a lung disease characterized by abnormal overgrowth of smooth muscle-like tissue in the lungs, causing coughing, shortness of breath, chest pain, and lung collapse.
Skin Abnormalities
Virtually all affected people have skin abnormalities, including:
- Patches of unusually light-colored skin
- Areas of raised and thickened skin
- Growths under the nails
- Tumors on the face called facial angiofibromas, common beginning in childhood.
Sometimes, affected individuals have areas of bone or dental damage.
Frequency
Tuberous sclerosis complex affects 1 in 6,000 to 10,000 people.
Other Names for This Condition
- Bourneville disease
- Bourneville phakomatosis
- Cerebral sclerosis
- Sclerosis tuberosa
- Tuberose sclerosis
Causes & Inheritance
Variants (also known as mutations) in the TSC1 or TSC2 gene can cause tuberous sclerosis complex. The TSC1 and TSC2 genes provide instructions for making the proteins hamartin and tuberin, respectively. These two proteins work together within cells to help regulate cell growth and division (proliferation) and cell size, acting as tumor suppressors that normally prevent cells from growing and dividing too fast or in an uncontrolled way.
People with tuberous sclerosis complex are born with one altered copy of the TSC1 gene or the TSC2 gene in each cell. For tumors to develop, a second change involving the other copy of the TSC1 or TSC2 gene must occur in cells during a person's lifetime. The absence of hamartin or tuberin in different types of cells leads to the growth of tumors in many different organs and tissues.
Inheritance Pattern
Tuberous sclerosis complex has an autosomal dominant pattern of inheritance, meaning one copy of the altered gene in each cell is sufficient to increase the risk of developing tumors and other problems. About one-third of cases are inherited, while the remaining two-thirds are sporadic, resulting from new variants in the TSC1 or TSC2 gene.
Rarely, individuals may not have an identified variant in these genes, suggesting the condition could be caused by a random variant occurring very early in development, leading to mosaicism (some cells with a normal gene, others with an altered version).