Tuberous Sclerosis 2
Disease Details
Family Health Simplified
- Description
- Tuberous sclerosis complex 2 is a genetic disorder characterized by the growth of benign tumors in multiple organs, including the brain, skin, kidneys, and heart.
- Type
- Tuberous sclerosis type 2 (TSC2) is a genetic disorder characterized by the growth of benign tumors in various organs. It follows an autosomal dominant pattern of genetic transmission. This means that a person only needs one copy of the altered gene from either parent to be affected by the disorder.
- Signs And Symptoms
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Tuberous sclerosis complex (TSC) is a genetic disorder that affects multiple organ systems due to the growth of benign tumors. Tuberous sclerosis is often divided into TSC1, caused by mutations in the TSC1 gene, and TSC2, caused by mutations in the TSC2 gene. Here are signs and symptoms:
### Signs and Symptoms
**Neurological:**
- Seizures
- Developmental delay
- Cognitive impairment
- Autism spectrum disorders
- Behavioral issues
**Dermatological:**
- Hypomelanotic macules (white patches on the skin)
- Facial angiofibromas (small, red bumps on the face)
- Shagreen patches (thickened, pebbly skin)
- Ungual fibromas (benign growths around or under the nails)
**Renal:**
- Angiomyolipomas (benign kidney tumors)
- Cystic kidney disease
**Pulmonary:**
- Lymphangioleiomyomatosis (LAM) (more common in females)
**Cardiac:**
- Rhabdomyomas (benign tumors of the heart in infants)
**Ophthalmologic:**
- Retinal hamartomas (benign growths in the retina)
Regular monitoring and a multidisciplinary approach to treatment are important for managing TSC. - Prognosis
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Tuberous Sclerosis Complex type 2 (TSC2) is a genetic disorder affecting multiple organ systems. The prognosis for individuals with TSC2 can vary significantly:
1. **Severity and Organ Involvement**: The severity of symptoms and which organs are affected can vary widely. Some people may have mild symptoms with few complications, while others can experience severe and life-threatening issues.
2. **Lifelong Condition**: It is a chronic condition requiring lifelong management and monitoring.
3. **Impact on Quality of Life**: With appropriate medical care, many individuals can lead a productive life. However, some may face significant challenges due to neuropsychiatric disorders, epilepsy, or renal issues.
4. **Mortality**: Life expectancy can be normal or reduced depending on the severity of complications, particularly in the kidneys, brain, and heart.
Early diagnosis and comprehensive management are critical for improving outcomes. Regular monitoring and tailored treatments can help manage symptoms and reduce the risks of complications. - Onset
- Tuberous sclerosis complex (TSC), which includes TSC2, typically has an onset in early childhood. However, the age of onset can vary widely, with some symptoms appearing at birth and others manifesting later in life.
- Prevalence
- Tuberous Sclerosis Complex, including Tuberous Sclerosis 2, has a prevalence of approximately 1 in 6,000 to 1 in 10,000 live births.
- Epidemiology
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Tuberous Sclerosis Complex (TSC) is a genetic disorder characterized by the growth of non-cancerous tumors in multiple organs. It is often caused by mutations in the TSC1 or TSC2 genes. Here’s a focused look at the epidemiology of TSC:
- **Prevalence**: The incidence of TSC is estimated to be approximately 1 in 6,000 live births, with a prevalence of around 1 in 20,000 individuals in the general population.
- **Age of Onset**: TSC can be diagnosed at any age, but signs and symptoms often appear in infancy or early childhood.
- **Gender**: TSC affects males and females equally.
- **Ethnicity**: TSC appears to have a similar prevalence across different ethnic and racial groups.
- **Heritability**: About two-thirds of TSC cases arise from new mutations, while the remaining third are inherited in an autosomal dominant pattern.
- **Genetic Factors**: Mutations in either the TSC1 gene (located on chromosome 9) or the TSC2 gene (located on chromosome 16) lead to the condition, with TSC2 mutations generally resulting in a more severe phenotype.
Understanding TSC’s epidemiology helps in early diagnosis, effective management, and improved outcomes for affected individuals. - Intractability
- Tuberous sclerosis complex (TSC), including tuberous sclerosis 2 (TSC2), can be intractable, meaning some aspects of the disease may be difficult to manage or treat. TSC is a genetic disorder that causes non-malignant tumors to form in many different organs, primarily the brain, eyes, heart, skin, kidneys, and lungs. While there are treatments to manage symptoms and complications, the condition is chronic and lifelong. Some individuals with TSC may experience intractable epilepsy, which is seizures that are difficult to control with medication. Therefore, in some cases, aspects of TSC can be intractable.
- Disease Severity
- Tuberous sclerosis complex (TSC) is a genetic disorder with variable disease severity. It can cause benign tumors to grow in many parts of the body, including the brain, skin, kidneys, heart, and lungs. The severity of symptoms can range from mild to severe, depending on the number, type, and location of the tumors, and can affect every individual differently.
- Healthcare Professionals
- Disease Ontology ID - DOID:0080325
- Pathophysiology
- Tuberous sclerosis complex (TSC), which includes tuberous sclerosis 2 (TSC2), is a genetic disorder characterized by the growth of benign tumors in multiple organs. The condition stems from mutations in the TSC2 gene, which encodes the tuberin protein. Tuberin, along with hamartin (produced by the TSC1 gene), forms a complex that inhibits the mammalian target of rapamycin (mTOR) pathway. The mTOR pathway is crucial for cell growth and proliferation. Mutations in TSC2 lead to hyperactivation of mTOR, causing abnormal cell growth and the formation of benign tumors in organs such as the brain, skin, kidneys, heart, and lungs. This dysfunction results in the various clinical manifestations of TSC.
- Carrier Status
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Tuberous Sclerosis Complex (TSC) is an autosomal dominant genetic disorder caused by mutations in one of two genes: TSC1 or TSC2. Specifically for TSC2:
- **Carrier Status**: In an autosomal dominant disorder like TSC, if a person carries a mutation in TSC2, they generally manifest some form of the disease. There are no unaffected carriers, as having one mutated copy of the gene is usually sufficient to cause symptoms.
- **Nan**: This term is not applicable in the context of genetic information. If "nan" refers to "not a number" or is a placeholder for additional information, there is no relevant information to add related to TSC2 beyond the genetic context provided. - Mechanism
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Tuberous sclerosis complex (TSC) is a genetic disorder caused by mutations in either the TSC1 or TSC2 genes. Tuberous sclerosis 2 specifically refers to cases involving mutations in the TSC2 gene. The TSC1 gene encodes hamartin, while the TSC2 gene encodes tuberin. These two proteins form a complex that acts as a key regulator of cell growth and proliferation.
**Mechanism:**
Mutations in the TSC2 gene lead to defective tuberin protein, disrupting the TSC1-TSC2 complex's function. Normally, this complex inhibits the mechanistic target of rapamycin (mTOR) pathway, a central regulator of cell growth and proliferation. When tuberin is dysfunctional, mTOR activity is unchecked, resulting in increased cell growth, cell proliferation, and the formation of benign tumors (hamartomas) in various organs.
**Molecular mechanisms:**
1. **Loss of Function in TSC2:** Mutations of TSC2 result in loss of function of tuberin, compromising the formation and regulatory action of the TSC1-TSC2 complex.
2. **Activation of mTOR Pathway:** The defective TSC1-TSC2 complex fails to inhibit the mTOR pathway, leading to hyperactivation. The mTOR pathway controls protein synthesis, cell growth, and autophagy, contributing to abnormal cell proliferation and growth.
3. **Cellular and Clinical Manifestations:** The unchecked mTOR activity results in the development of benign tumors in multiple organs such as the brain, skin, kidneys, heart, and lungs. Neurological manifestations like seizures, developmental delay, and autism spectrum disorder are also common.
Therapeutics targeting the mTOR pathway, such as mTOR inhibitors (e.g., everolimus), are used to manage symptoms and reduce the size of some tumors in patients with tuberous sclerosis complex. - Treatment
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Tuberous Sclerosis Complex (TSC) 2, a genetic disorder, often requires a multidisciplinary approach for treatment. Management typically includes:
- **Medication:** mTOR inhibitors like everolimus can reduce the size of certain tumors. Antiepileptic drugs (AEDs) are used for seizure control.
- **Surgery:** Surgical intervention may be necessary for removing tumors or treating epilepsy unresponsive to medication.
- **Therapies:** Physical, occupational, and speech therapies address developmental issues.
- **Regular monitoring:** Routine check-ups for kidney, brain, skin, and heart health are vital due to the potential for related complications. - Compassionate Use Treatment
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For Tuberous Sclerosis Complex (TSC), including TSC2:
**Compassionate Use Treatment:**
- Compassionate use programs may allow access to investigational drugs for patients with serious conditions who have no other treatment options. Physicians can apply to relevant regulatory authorities and pharmaceutical companies on behalf of their patients for access to such treatments, which may include newer mTOR inhibitors or other targeted therapies.
**Off-label or Experimental Treatments:**
1. **Everolimus**: Originally approved for specific cancer treatments, Everolimus is used off-label for various manifestations of TSC, such as subependymal giant cell astrocytomas (SEGAs) and renal angiomyolipomas, leveraging its mTOR inhibiting properties.
2. **Sirolimus**: Another mTOR inhibitor that has shown promise in treating TSC-related lesions, although not officially approved for TSC-related indications.
3. **Aripiprazole**: Sometimes used off-label to manage behavioral and neuropsychiatric symptoms associated with TSC.
4. **Cannabidiol (CBD)**: An experimental approach for managing epilepsy in TSC, with some evidence suggesting it can reduce seizure frequency.
5. **Gene Therapy**: Still in early stages of development, gene therapy aims to correct the underlying genetic mutations causing TSC and holds potential as a future treatment.
Consultation with a healthcare provider who specializes in TSC is essential to explore these and any other emerging treatments. - Lifestyle Recommendations
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For Tuberous Sclerosis Complex (TSC), lifestyle recommendations can play a significant role in managing the condition. Though there's no cure, the following strategies can help optimize the quality of life:
1. **Regular Medical Checkups:** Continuous monitoring by healthcare professionals is crucial for early detection and management of complications.
2. **Medication Adherence:** Taking prescribed medications to manage seizures, skin abnormalities, and other symptoms.
3. **Healthy Diet and Exercise:** Maintaining a balanced diet and regular physical activity can promote overall well-being.
4. **Education and Occupational Support:** Tailored educational programs and vocational training can help individuals reach their full potential.
5. **Mental Health Care:** Seeking support for mental health, including counseling or therapy, to manage stress, anxiety, or depression.
6. **Family Support and Education:** Educate family members about the condition to create a supportive home environment.
7. **Avoiding Triggers:** Identifying and avoiding factors that may trigger seizures or other symptoms, such as certain lights or stress.
8. **Routine Screenings:** Regular screenings for potential complications like renal or cardiac issues.
Consulting with a healthcare provider is essential to create a personalized management plan. - Medication
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Tuberous sclerosis complex (TSC) is a genetic disorder characterized by the growth of benign tumors in various organs. Tuberous sclerosis complex has two genetic forms: TSC1 and TSC2. For TSC2, the medication options, similar to TSC1, focus on managing symptoms and include:
1. **Everolimus (Afinitor)**: An mTOR inhibitor that can reduce the size of certain tumors associated with TSC, such as those in the brain (subependymal giant cell astrocytomas) and kidneys (angiomyolipomas).
2. **Sirolimus (Rapamune)**: Another mTOR inhibitor, sometimes used off-label to treat TSC-related symptoms and tumors.
These medications help control the growth of tumors by inhibiting the mTOR pathway, which is often overactive in TSC patients. Always consult with a healthcare provider for personalized treatment options. - Repurposable Drugs
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For Tuberous Sclerosis Complex 2 (TSC2), potential repurposable drugs include:
1. **Sirolimus (Rapamycin)**: Initially used as an immunosuppressant, it has shown efficacy in reducing the size of tuberous sclerosis-associated tumors.
2. **Everolimus**: Originally used to treat certain cancers, it has been effective in treating subependymal giant cell astrocytomas (SEGAs) associated with TSC.
3. **Metformin**: Typically used to treat type 2 diabetes, it has potential benefits in TSC due to its effects on cellular growth pathways.
No additional information or non-applicable (nan) data is provided. - Metabolites
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Tuberous sclerosis complex (TSC), including TSC2, is associated with abnormalities in several metabolic pathways. Some notable metabolites involved include:
1. **mTOR Pathway Metabolites:** These are crucial metabolites influenced by the mammalian target of rapamycin (mTOR) signaling pathway, which is dysregulated in TSC. Key metabolites include amino acids, particularly leucine, glutamine, and others that activate mTOR signaling.
2. **Lipid Metabolism:** TSC2 mutations can affect lipid metabolism, leading to aberrant lipid accumulation or signaling. Key metabolites include various phospholipids and fatty acids.
3. **Glycolysis and Gluconeogenesis Intermediates:** Dysregulation of glucose metabolism is common, affecting levels of metabolites such as glucose-6-phosphate, fructose-1,6-bisphosphate, and pyruvate.
4. **Nucleotide Synthesis Metabolites:** Since TSC2 impacts cell growth and proliferation, metabolites involved in nucleotide synthesis, such as ribose-5-phosphate and inosine monophosphate (IMP), can be affected.
Addressing these metabolic disturbances can be important for understanding and potentially treating TSC2-related symptoms. - Nutraceuticals
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Nutraceuticals are food-derived products that offer health benefits beyond basic nutrition, and they may play a role in managing diseases, including Tuberous Sclerosis Complex (TSC). However, there is limited evidence on the effectiveness of specific nutraceuticals in the treatment of TSC. Patients should consult healthcare providers before adding any nutraceuticals to their regimen.
"nan" might indicate that detailed information on nanotechnology applications specifically for TSC2 is not available or wasn't specified. However, nanotechnology is an emerging field with the potential for targeted drug delivery and advanced treatment strategies for various genetic disorders. Research is ongoing to explore these possibilities. - Peptides
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Tuberous sclerosis complex (TSC) is a genetic disorder that can cause non-cancerous (benign) tumors to form in many different organs. Mutations in either of two genes, TSC1 or TSC2, are responsible for the disorder. TSC2 mutations are particularly linked to a more severe form of the disease.
Specific peptides or nanotherapeutics are not standard treatments for TSC2-related manifestations. Management primarily includes medications to control symptoms, surgical interventions for tumor removal, and targeted therapies like mTOR inhibitors (e.g., everolimus) to manage growths.
Research continues into novel therapeutics, including peptide-based and nanotech approaches, but these are not yet standard clinical practice. Always consult a medical professional for the most current and personalized medical advice.