Familial tumour syndromes of the nervous system
- Topic
Some families inherit a faulty tumour-suppressor gene that causes many nervous system tumours along with skin and organ signs.
What it is
Several autosomal dominant syndromes predispose to tumours of the nervous system. Each is caused by loss of a tumour suppressor gene, so a second hit in a cell starts a tumour (the two-hit model). Neurofibromatosis type 1 brings neurofibromas and optic gliomas; neurofibromatosis type 2 (NF2-related schwannomatosis) brings bilateral vestibular schwannomas and meningiomas. Tuberous sclerosis gives cortical tubers and subependymal tumours with epilepsy, and von Hippel-Lindau gives hemangioblastomas of the cerebellum and retina with kidney cancer.
Structure
- Cortical tuber: firm area of disorganised cortex with giant bizarre neurons and astrocytes, a cause of epilepsy.
- Hemangioblastoma: cyst with a mural nodule of thin-walled capillaries and lipid-laden stromal cells that make erythropoietin.
- Vestibular schwannoma: Antoni A (cellular, Verocay bodies) and Antoni B (loose) areas, S100 positive.
Familial tumour syndromes of the nervous system
| Syndrome | Gene and protein | CNS tumours | Other features |
|---|---|---|---|
| Neurofibromatosis type 1 | NF1, neurofibromin (RAS off-switch) | Optic pathway pilocytic astrocytoma, other gliomas | Café-au-lait spots, neurofibromas, Lisch nodules, MPNST |
| Neurofibromatosis type 2 | NF2, merlin | Bilateral vestibular schwannomas, meningiomas, ependymomas | Juvenile cataract |
| Schwannomatosis | SMARCB1, LZTR1 | Multiple schwannomas | Pain |
| Tuberous sclerosis complex | TSC1 hamartin, TSC2 tuberin | Cortical tubers, subependymal giant cell astrocytoma | Angiofibromas, cardiac rhabdomyoma, angiomyolipoma |
| Von Hippel-Lindau | VHL (HIF regulation) | Cerebellar, spinal and retinal hemangioblastomas | Clear cell RCC, pheochromocytoma, pancreatic cysts |
Clinical notes
- Genetic testing and surveillance imaging (brain, eyes, kidneys, adrenals) allow early treatment in affected families.
- mTOR inhibitors shrink subependymal giant cell astrocytomas and angiomyolipomas in tuberous sclerosis.
Test yourself
Think of the answer, then tap the question to see it.
What tumours are the hallmark of neurofibromatosis type 2?
Bilateral vestibular schwannomas, often with meningiomas and spinal ependymomas.
Which pathway is overactive when TSC1 or TSC2 is lost?
The mTOR pathway, which drives cell growth.
Which CNS tumour is typical of von Hippel-Lindau disease?
Hemangioblastoma of the cerebellum, spinal cord or retina.
Elsewhere in DurgiPedia
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Neurofibromatosis type 1: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Tuberous sclerosis complex: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Von Hippel-Lindau syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.