Genomic coordinate 9:132,891,349
Here I present: “Tuberous Sclerosis Complex”, Victor McKusick, Mendelian Inheritance in Man’, 1966. 結節性硬化症。icd10=Q85.1
INTRODUCTION.
Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterized by hamartomas in multiple organ systems, including the brain, skin, heart, kidneys, and lung. Central nervous system (CNS) manifestations include epilepsy, learning difficulties, behavioral problems, and autism. Renal lesions, usually angiomyolipomas, can cause clinical problems secondary to hemorrhage or by compression and replacement of healthy renal tissue, which can cause renal failure. Patients can also develop renal cysts and renal-cell carcinomas. Pulmonary lymphangioleiomyomatosis can develop in the lungs. Skin lesions include melanotic macules, facial angiofibromas, and patches of connective tissue nevi. There is a wide clinical spectrum, and some patients may have minimal symptoms with no neurologic disability.
Tuberous Sclerosis Complex (TSC) Overview.
Tuberous sclerosis complex (TSC) is a genetic neurocutaneous disorder characterized by benign tumors ( hamartomas ) in multiple organs. It has a highly variable presentation — from mild skin findings to severe neurological disease.
1. Cause
Mutation in either:
TSC1 gene → encodes hamartin.
TSC2 gene → encodes tuberin.
Both proteins form complex that inhibits mTOR pathway → regulates cell growth.
Loss leads to uncontrolled cell proliferation → hamartomas.
Inheritance:
Autosomal dominant
~2/3 of cases are de novo mutations.
2. Major Clinical Features (Organ System–Wise)
Integument (Skin)
Hypomelanotic macules (“ash leaf spots”).
Facial angiofibromas.
Shagreen patch (connective tissue nevus).
Periungual fibromas.
These are major diagnostic clues.
Brain / Neurological
Cortical tubers.
Subependymal nodules.
SEGA (subependymal giant cell astrocytoma).
Epilepsy (infantile spasms common).
Neurodevelopmental disorders:
Intellectual disability.
Autism spectrum features:
Behavioral dysregulation (TAND: TSC-associated neuropsychiatric disorders).
Kidneys
Angiomyolipomas (AMLs) — can hemorrhage.
Renal cysts.
Rarely: Polycystic kidney disease (TSC2/PKD1 contiguous deletion).
Heart
Cardiac rhabdomyomas
Often detected in utero
May regress with a
Lungs
LAM (lymphangioleiomyomatosis)
Mostly young adult females.
Progressive dyspnea, pneumothorax.
Eyes
Retinal hamartomas.
There is evidence that tuberous sclerosis complex is caused by mutation in the hamartin (TSC1) gene encoded on cytogenetic location 9q34.13 and genomic coordinate 9:132,891,349.
