Summary about Disease
Tuberous sclerosis complex (TSC) is a rare genetic disorder that causes non-cancerous (benign) tumors to grow in many parts of the body, including the brain, skin, kidneys, heart, lungs, and eyes. It affects people differently; some have very mild symptoms, while others experience significant disabilities. TSC is typically diagnosed in infancy or early childhood, but milder cases may go undetected until adulthood. There is no cure for TSC, and treatment focuses on managing symptoms and complications.
Symptoms
Symptoms of TSC vary widely in severity and can include:
Skin: Hypopigmented macules (white spots), facial angiofibromas (small red bumps on the face), shagreen patches (thickened, leathery skin), ungual fibromas (tumors around the fingernails or toenails).
Brain: Seizures, developmental delays, intellectual disability, autism spectrum disorder, behavioral problems, learning disabilities. Subependymal nodules (SENs) and subependymal giant cell astrocytomas (SEGAs) are types of brain tumors commonly seen.
Kidneys: Angiomyolipomas (tumors made of blood vessels, muscle, and fat), cysts. These can sometimes lead to kidney problems or bleeding.
Heart: Cardiac rhabdomyomas (tumors in the heart muscle), typically present at birth and often shrink over time.
Lungs: Lymphangioleiomyomatosis (LAM) can occur, particularly in women.
Eyes: Retinal hamartomas (tumors on the retina).
Other: Dental enamel pits, gum fibromas.
Causes
TSC is caused by mutations in one of two genes: TSC1 (encoding hamartin) or *TSC2* (encoding tuberin). These genes act as tumor suppressors, regulating cell growth and proliferation. Mutations in these genes lead to uncontrolled cell growth and the formation of tumors. The genetic mutation can be inherited from a parent with TSC (autosomal dominant inheritance), or it can occur as a new (de novo) mutation in the affected individual. Approximately two-thirds of cases are the result of new mutations.
Medicine Used
4. Medicine used There is no cure for TSC, so treatment focuses on managing symptoms and preventing complications. Medications used may include:
Antiepileptic drugs (AEDs): To control seizures. Several different types of AEDs may be used, depending on the type of seizures.
mTOR inhibitors (e.g., everolimus, sirolimus): To shrink tumors in the brain, kidneys, and other organs. These drugs block the mammalian target of rapamycin (mTOR) pathway, which is overactive in TSC.
Topical sirolimus: For facial angiofibromas.
Medications for behavioral problems: Stimulants, antidepressants, or antipsychotics may be used to manage behavioral issues associated with TSC, such as ADHD, anxiety, or aggression.
Other medications: To treat specific complications, such as high blood pressure or kidney problems.
Is Communicable
TSC is NOT communicable. It is a genetic disorder, not an infectious disease. It cannot be spread from person to person through any means.
Precautions
Since TSC is a genetic disorder, there are no specific precautions to prevent it from occurring in an individual. However, for individuals with TSC and their families, the following precautions are important:
Regular medical check-ups: To monitor for the development or progression of tumors and other complications.
Genetic counseling: For individuals with TSC and their families, to understand the risk of passing the condition on to future generations.
Early intervention services: For children with TSC, to address developmental delays and learning disabilities.
Skin protection: To prevent sunburn, especially in areas with hypopigmented macules.
Management of seizures: To prevent injuries.
Cardiology monitoring: Due to the possibility of cardiac rhabdomyomas, or related heart conditions.
How long does an outbreak last?
TSC is not an "outbreak" type of disease. It is a chronic, lifelong condition. While specific symptoms, like seizures or skin lesions, may fluctuate in severity over time, the underlying genetic disorder is always present. Tumors associated with TSC may grow, shrink, or remain stable over time.
How is it diagnosed?
TSC is diagnosed based on a combination of clinical criteria (physical examination and medical history) and genetic testing. The diagnostic criteria are categorized into major and minor features. A definite diagnosis of TSC requires either:
Two major features, or
One major feature with two or more minor features, or
Identification of a TSC1 or *TSC2* pathogenic variant on genetic testing. Major Features:
Hypomelanotic macules (≥ 3)
Angiofibromas (≥ 3) or cephalic plaque
Ungual or periungual fibroma (≥ 2)
Shagreen patch
Multiple retinal hamartomas
Cortical dysplasias including tubers and white matter radial migration lines
Subependymal nodules (≥ 2)
Subependymal giant cell astrocytoma (SEGA)
Cardiac rhabdomyoma, single or multiple
Lymphangioleiomyomatosis (LAM)
Angiomyolipoma (≥ 2) Minor Features:
Multiple dental enamel pits (≥ 3)
Hamartomatous rectal polyps
Bone cysts
Cerebral white matter radial migration lines
Gingival fibromas (≥ 2)
Nonrenal hamartoma
Retinal achromic patch
"Confetti" skin lesions
Multiple renal cysts Diagnostic testing may include:
Physical examination: To assess for skin lesions and other physical features.
Neurological examination: To assess for seizures, developmental delays, and other neurological problems.
Imaging studies: MRI of the brain, CT scan or ultrasound of the kidneys, echocardiogram of the heart, and eye exam to look for tumors.
Genetic testing: To confirm the diagnosis and identify the specific gene mutation.
Timeline of Symptoms
9. Timeline of symptoms The timeline of symptoms in TSC can vary greatly from person to person. Some individuals may be diagnosed in infancy due to seizures or cardiac rhabdomyomas, while others may not be diagnosed until adulthood when symptoms such as kidney tumors or LAM are discovered. Here is a general overview:
Prenatal/Infancy: Cardiac rhabdomyomas are often detected prenatally or shortly after birth. Seizures may begin in infancy. White spots on the skin may be present at birth or appear in early infancy.
Childhood: Developmental delays, intellectual disability, autism spectrum disorder, and behavioral problems may become apparent in childhood. Facial angiofibromas typically appear during childhood.
Adolescence/Adulthood: Kidney tumors (angiomyolipomas) and lung involvement (LAM, primarily in females) may develop during adolescence or adulthood. Ungual fibromas and shagreen patches may also become more prominent. The severity of symptoms can change over time. Some tumors may grow, while others may shrink or remain stable.
Important Considerations
Variability: The severity of TSC symptoms varies widely. Some individuals have mild symptoms and lead relatively normal lives, while others experience significant disabilities.
Lifelong condition: TSC is a lifelong condition that requires ongoing medical management.
Multidisciplinary care: Management of TSC often requires a team of specialists, including neurologists, dermatologists, nephrologists, cardiologists, pulmonologists, and geneticists.
Genetic counseling: Genetic counseling is important for individuals with TSC and their families to understand the inheritance pattern and the risk of passing the condition on to future generations.
Early intervention: Early intervention services are crucial for children with TSC to address developmental delays and learning disabilities.
Research: Ongoing research is focused on developing new treatments for TSC and improving the quality of life for individuals with the condition.
TSC Clinics: TSC clinics that specialize in TSC are available to provide the best medical care.
Support: TSC Alliance is a great resource for support.