Last updated 2mo ago
An infant with infantile spasms is found to have hypopigmented macules (ash-leaf spots) and cardiac rhabdomyomas. Brain MRI shows cortical tubers and subependymal nodules.
AD; TSC1 (hamartin) or TSC2 (tuberin) - tumor suppressors, mTOR pathway
- ~2/3 de novo
- Skin: ash-leaf spots (hypopigmented macules), facial angiofibromas, shagreen patches, ungual fibromas
- Brain: cortical tubers, subependymal nodules → subependymal giant cell astrocytomas (SEGA), seizures
- Heart: cardiac rhabdomyomas
- Kidney: angiomyolipomas, cysts
- Lung: lymphangioleiomyomatosis (LAM) - females
- Clinical diagnosis by consensus criteria, combining major features (e.g., ≥3 hypomelanotic macules, angiofibromas, cortical tubers, subependymal nodules, SEGA, cardiac rhabdomyoma, angiomyolipomas) and minor features
- A pathogenic TSC1 or TSC2 variant is independently diagnostic, regardless of clinical findings
- Baseline workup at diagnosis: brain MRI, EEG, echocardiogram, renal imaging, dilated eye exam, and skin/dental exam
- Molecular testing of TSC1/TSC2 confirms the diagnosis and enables family and prenatal/preimplantation testing
- mTOR inhibitors (everolimus, sirolimus) for SEGA, angiomyolipomas, LAM
This table summarizes cardiac tumors and their associated genetic syndromes, a clinically central area to know.
"IS with TS": Infantile spasms are the most common seizure type in tuberous sclerosis. Vigabatrin is first-line treatment for infantile spasms associated with TS.
"In TS, you become a Teen Soon": CNS hamartomas can cause precocious puberty.
"Hammar Time": TSC1 encodes hamartin ("9" looks like a hammer), TSC2 encodes tuberin. Together they form the hamartoma-causing complex.
"mTOR inhibiTOR for TubORous sclerosis": Sirolimus (rapamycin) and everolimus are used to treat SEGAs, angiomyolipomas, and LAM.
"Top cause of death in TS are Tumors causing Seizures": #1 cause of death is CNS tumors leading to seizures; #2 is renal failure.