[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Central nervous system](https://durgical.com/en/general-pathology/areas/cns/) › Familial tumour syndromes of the nervous system # 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. Updated Nov 12, 2026 ## Key points - NF1 (NF1 gene, neurofibromin, a RAS GTPase-activating protein, chromosome 17): café-au-lait spots, axillary freckling, neurofibromas, Lisch nodules, optic pathway glioma, risk of malignant nerve sheath tumour. - NF2 (NF2 gene, merlin, chromosome 22): bilateral vestibular schwannomas, meningiomas, spinal ependymomas, juvenile cataract. - Schwannomatosis: multiple schwannomas without vestibular ones; SMARCB1 or LZTR1. - Tuberous sclerosis (TSC1 hamartin, TSC2 tuberin; mTOR overactive): cortical tubers, subependymal nodules and giant cell astrocytoma, seizures, angiofibromas, cardiac rhabdomyoma, renal angiomyolipoma. - Von Hippel-Lindau (VHL, chromosome 3p; HIF not degraded): cerebellar and retinal hemangioblastomas, clear cell renal cell carcinoma, pheochromocytoma, pancreatic cysts and neuroendocrine tumours; polycythemia from erythropoietin. ## 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](https://durgical.com/en/conditions/neurofibromatosis/) | NF1, neurofibromin (RAS off-switch) | Optic pathway pilocytic astrocytoma, other gliomas | Café-au-lait spots, neurofibromas, Lisch nodules, MPNST | | [Neurofibromatosis type 2](https://durgical.com/en/conditions/vestibular-schwannoma/) | NF2, merlin | Bilateral vestibular schwannomas, meningiomas, ependymomas | Juvenile cataract | | Schwannomatosis | SMARCB1, LZTR1 | Multiple schwannomas | Pain | | [Tuberous sclerosis complex](https://durgical.com/en/conditions/tuberous-sclerosis-complex/) | TSC1 hamartin, TSC2 tuberin | Cortical tubers, subependymal giant cell astrocytoma | Angiofibromas, cardiac rhabdomyoma, angiomyolipoma | | [Von Hippel-Lindau](https://durgical.com/en/conditions/renal-cell-carcinoma/) | 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. ## Memory aid NF1 on 17 (seventeen letters in ‘von Recklinghausen’), NF2 on 22 (two ears, two schwannomas), VHL on 3 (three letters). ## 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. [Add to my cards (3)](https://durgical.app/estudiar/?add=/en/general-pathology/familial-tumour-syndromes-of-the-nervous-system/) [More Pathology questions →](https://durgical.com/en/practice/?f=pathology) ## Elsewhere in DurgiPedia - [Neural crest cells and their derivatives](https://durgical.com/en/embryology/neural-crest-cells-and-their-derivatives/) ## Connections ## Related 8 - [Schwannoma and neurofibromatosis type 2](https://durgical.com/en/general-pathology/schwannoma-and-neurofibromatosis-type-2/) - [Neurofibroma, NF1 and MPNST](https://durgical.com/en/general-pathology/neurofibroma-nf1-and-mpnst/) - [Pilocytic astrocytoma](https://durgical.com/en/general-pathology/pilocytic-astrocytoma/) - [Meningioma](https://durgical.com/en/general-pathology/meningioma/) - [Clear cell renal cell carcinoma](https://durgical.com/en/general-pathology/clear-cell-renal-cell-carcinoma/) - [Pheochromocytoma and paraganglioma](https://durgical.com/en/general-pathology/pheochromocytoma-and-paraganglioma/) - [Hereditary cancer syndromes: the table to know](https://durgical.com/en/general-pathology/hereditary-cancer-syndromes-the-table-to-know/) - [Tumour suppressor genes: RB, TP53, APC, BRCA and the two-hit hypothesis](https://durgical.com/en/general-pathology/tumour-suppressor-genes-rb-tp53-apc-brca-and-the-two-hit-hypothesis/) ## Related conditions 6 - [Neurofibromatosis (types 1 and 2)](https://durgical.com/en/conditions/neurofibromatosis/) - [Tuberous sclerosis complex](https://durgical.com/en/conditions/tuberous-sclerosis-complex/) - [Vestibular schwannoma (acoustic neuroma)](https://durgical.com/en/conditions/vestibular-schwannoma/) - [Renal cell carcinoma](https://durgical.com/en/conditions/renal-cell-carcinoma/) - [Phaeochromocytoma](https://durgical.com/en/conditions/phaeochromocytoma/) - [Meningioma](https://durgical.com/en/conditions/meningioma/) [← All of general pathology](https://durgical.com/en/general-pathology/) 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](https://medlineplus.gov/genetics/condition/neurofibromatosis-type-1/) (MedlinePlus, US National Library of Medicine, 2026); [Tuberous sclerosis complex: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/tuberous-sclerosis-complex/) (MedlinePlus, US National Library of Medicine, 2026); [Von Hippel-Lindau syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/von-hippel-lindau-syndrome/) (MedlinePlus, US National Library of Medicine, 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/general-pathology/familial-tumour-syndromes-of-the-nervous-system/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/familial-tumour-syndromes-of-the-nervous-system/