Genetics:
• It is caused by mutations in the TSC1 or TSC2 genes.
• These genes code for proteins hamartin and tuberin, respectively, which help regulate cell growth and proliferation.
• It is inherited in an autosomal dominant manner, but many cases are due to new (de novo) mutations.
Clinical Features:
Skin-
• Hypomelanotic macules (ash-leaf spots)
• Facial angiofibromas (adenoma sebaceum)
• Shagreen patches (thickened, leathery skin)
• Periungual fibromas
Neurological-
• Seizures (often infantile spasms)
• Intellectual disability
• Developmental delay
• Autism spectrum disorders
Kidneys-
• Renal angiomyolipomas
• Cysts: Potential for renal cell carcinoma
Heart-
• Cardiac rhabdomyomas, which may cause arrhythmias or obstruction.
Lungs-
• Lymph angioleiomyomatosis (LAM), Leading to progressive lung disease
Eyes-
• Retinal hamartomas
Treatment:
mTOR inhibitors (e.g., Sirolimus, Temsirolimus)
|
Associated Genes |
Gene Location |
Inheritance Pattern |
|
TSC1 (Hamartin) |
Chromosome 9q34 |
Autosomal Dominant |
|
TSC2 (Tuberin) |
Chromosome 16p13.3 |
Autosomal Dominant |
q - long arm
P - short arm