Tuberous Sclerosis Flashcards
What is tuberous sclerosis (TS)?
A rare genetic disorder characterized by the development of benign tumors in multiple organ systems, including the skin, brain, kidneys, heart, and lungs.
What is the primary cause of TS?
Mutations in the TSC1 or TSC2 genes, leading to dysregulation of the mTOR pathway and abnormal cell growth.
What is the inheritance pattern of TS?
Autosomal dominant, though many cases arise de novo.
At what age is TS typically diagnosed?
Often in childhood, but the presentation can vary based on the severity of organ involvement.
What role do TSC1 and TSC2 genes play in TS?
These genes encode hamartin (TSC1) and tuberin (TSC2), which inhibit the mTOR pathway. Mutations result in unchecked cell growth and hamartoma formation.
What organs are commonly affected in TS?
Brain, skin, kidneys, heart, lungs, and eyes.
What are the major neurological features of TS?
Cortical tubers: Benign brain lesions causing seizures and developmental delays.
Subependymal nodules (SENs): Can progress to subependymal giant cell astrocytomas (SEGAs).
Epilepsy: Often presenting as infantile spasms or focal seizures.
Neurodevelopmental disorders: Autism spectrum disorder (ASD) and intellectual disability.
What renal complications are associated with TS?
Renal angiomyolipomas (AMLs): Benign tumors that can cause bleeding or renal failure.
Cysts.
Rarely, renal cell carcinoma.
What cardiac findings are seen in TS?
Rhabdomyomas: Benign heart tumors often diagnosed prenatally or in infancy.
May cause arrhythmias or obstruction of blood flow.
What pulmonary condition is associated with TS?
Lymphangioleiomyomatosis (LAM): A progressive lung disease causing cystic changes and respiratory symptoms, more common in adult females.
What ocular findings are seen in TS?
Retinal hamartomas (astrocytic hamartomas), which are usually asymptomatic but can cause visual impairment in rare cases.
How is tuberous sclerosis diagnosed?
Based on clinical criteria (major and minor features) or genetic testing confirming TSC1 or TSC2 mutations.
What are the major diagnostic criteria for TS?
Cortical tubers.
Subependymal nodules.
Facial angiofibromas or forehead plaques.
Hypomelanotic macules (≥3).
Shagreen patches.
Renal angiomyolipomas.
Cardiac rhabdomyomas.
Retinal hamartomas.
Lymphangioleiomyomatosis (LAM).
Ungual fibromas.
What imaging studies are used to assess TS?
Brain MRI: To detect cortical tubers, SENs, or SEGAs.
Renal ultrasound/MRI: For angiomyolipomas.
CT/MRI of the chest: For LAM.
What genetic tests confirm TS?
Detection of mutations in TSC1 or TSC2 genes.
How are seizures in TS managed?
Antiepileptic drugs (AEDs): Vigabatrin is first-line for infantile spasms.
mTOR inhibitors: Everolimus for refractory seizures or SEGAs.
Surgery for drug-resistant epilepsy.
How are subependymal giant cell astrocytomas (SEGAs) treated?
Everolimus (mTOR inhibitor) is the preferred therapy.
Surgical resection if causing hydrocephalus or mass effect.
How are renal angiomyolipomas managed?
mTOR inhibitors (e.g., everolimus) for large or symptomatic AMLs.
Embolization or nephrectomy for uncontrolled bleeding.
How are cardiac rhabdomyomas treated?
Observation for asymptomatic cases (many regress spontaneously).
Medical or surgical intervention for symptomatic cases.
How is lymphangioleiomyomatosis (LAM) treated?
mTOR inhibitors (e.g., sirolimus).
Oxygen therapy for advanced cases.
Lung transplantation in severe cases.
What supportive therapies are important in TS?
Developmental and behavioral interventions (e.g., for ASD or intellectual disability).
Dermatologic treatments (e.g., laser therapy for facial angiofibromas).
Regular screening and monitoring for complications.
What is the prognosis for tuberous sclerosis?
Highly variable; depends on the severity of organ involvement. Many patients live into adulthood with proper management.
What regular screenings are recommended for TS patients?
Annual brain MRI (in children).
Renal imaging every 1–3 years.
Cardiac echocardiography in children.
Pulmonary imaging and function tests in adults, especially females.
