Hub overviewCancer predispositionICD-10 various
Cancer syndromes — overview
Cancer-predisposition syndromes · hereditary cancer syndromes · familial cancer syndromes
Cancer-predisposition syndromes are inherited genetic disorders that confer markedly elevated lifetime risks of one or more malignancies. Skin oncology intersects with many — Gorlin, Brooke-Spiegler, Cowden, BAP1-TPDS, FAP / Gardner, Li-Fraumeni, NF1 / 2, TSC, xeroderma pigmentosum, Werner, Bloom, Fanconi, MEN-2B, MUTYH-associated polyposis. This page is a navigational hub linking to individual monographs.
CurrentLast reviewed 16 May 2026
Principles
- Hereditary cancer syndromes account for ~5-10% of malignancies overall.
- Suspect when:
- Multiple primary tumours in a single individual.
- Young age at cancer diagnosis.
- Multiple affected first-degree relatives.
- Bilateral / multifocal tumours.
- Specific tumour combinations (e.g. melanoma + pancreatic + mesothelioma).
- Cutaneous markers of a syndrome (BCC nests, mucosal neuromas, hamartomas).
- UK NHS Genomic Medicine Service / Cancer Genetics; testing via R-codes.
- Counsel before testing; cascade family screening; surveillance protocols essential.
Skin-oncology-relevant cancer syndromes (alphabetic)
- Ataxia-telangiectasia — ATM; cerebellar ataxia, telangiectasia, lymphoma.
- BAP1-TPDS — BAP1, uveal melanoma, mesothelioma, RCC, cutaneous melanoma.
- Bazex-Dupré-Christol — multiple BCC, follicular atrophoderma, hypotrichosis.
- Birt-Hogg-Dubé — fibrofolliculomas, lung cysts, RCC; FLCN.
- Bloom syndrome — BLM; growth failure, photosensitivity, multiple cancers.
- Brooke-Spiegler — multiple cylindromas, trichoepitheliomas; CYLD.
- Cardio-facio-cutaneous (CFC) — RAS-MAPK; multiple naevi.
- Carney complex — PRKAR1A; lentigines, myxoma, endocrine.
- Cowden syndrome (PTEN hamartoma) — PTEN; trichilemmomas, breast / endometrial / thyroid.
- Dyskeratosis congenita — telomeropathy; reticulate hyperpigmentation, oral leukoplakia, SCC, MDS.
- Familial melanoma (CDKN2A / CDK4 / MITF E318K).
- Fanconi anaemia — FANC genes; aplastic anaemia, AML, head & neck SCC.
- Gardner syndrome / FAP — APC; colonic adenomas, desmoids, epidermoid cysts.
- Gorlin syndrome — PTCH1 / SUFU; multiple BCCs, jaw cysts, palmar pits.
- Hermansky-Pudlak — OCA + bleeding + pulmonary fibrosis.
- HLRCC / Reed syndrome — FH; piloleiomyomas, uterine fibroids, type-2 papillary RCC.
- Howel-Evans — RHBDF2; PPK + oesophageal SCC.
- LEOPARD / Noonan — RAS-MAPK; lentigines, cardiomyopathy.
- Li-Fraumeni syndrome — TP53; sarcoma, breast, brain, adrenocortical, melanoma.
- MEN-2B — RET; mucosal neuromas, medullary thyroid Ca, phaeochromocytoma.
- Muir-Torre — MLH1 / MSH2 / MSH6 / PMS2; sebaceous neoplasms, GI / GU cancers.
- Neurofibromatosis type 1 — NF1; CALMs, neurofibromas, optic glioma.
- Oculocutaneous albinism — TYR / OCA2 / etc.; cSCC / BCC risk.
- Olmsted syndrome — TRPV3; PPK + periorificial keratoderma + cSCC risk.
- Peutz-Jeghers — STK11; mucocutaneous lentigines, GI hamartomas.
- Rombo syndrome — vermiculate atrophoderma + BCC.
- Rothmund-Thomson — RECQL4; poikiloderma, osteosarcoma.
- Schimmelpenning — mosaic HRAS / KRAS; naevus sebaceus + CNS / ocular.
- Tuberous sclerosis — TSC1 / TSC2; angiofibroma, ash-leaf, shagreen, lymphangioleiomyomatosis.
- Turcot syndrome — APC or MMR; colonic polyposis + CNS tumour.
- Werner syndrome — WRN; premature ageing, sarcoma, thyroid.
- Wiskott-Aldrich — WAS; eczema + thrombocytopenia + lymphoma.
- Xeroderma pigmentosum — XPA-G / V; severe photosensitivity, early cSCC / BCC / melanoma.
UK clinical genetics referral
- NHS Genomic Medicine Service (GMS): seven regional Genomic Laboratory Hubs.
- R-codes for cancer genetic testing:
- R206: Inherited polyposis.
- R207: Inherited gastrointestinal cancer.
- R208: Inherited colorectal cancer.
- R210: Inherited MMR / Lynch syndrome.
- R213: Inherited breast / ovarian cancer.
- R216: Inherited cancer susceptibility — multi-gene panel.
- R232: Familial pancreatic.
- R236: Inherited skin cancer susceptibility (Gorlin, BAP1-TPDS, melanoma).
- Manchester Score, Tyrer-Cuzick, BOADICEA for breast/ovarian risk; CanRisk integrated risk calculator.
- Cascade testing of first-degree relatives once mutation identified.
Surveillance principles
- Tailored to syndrome-specific tumour spectrum.
- Multidisciplinary clinics: clinical genetics, dermatology, GI, gynaecology, urology, neurology, ophthalmology, endocrinology, oncology.
- Cancer-specific imaging (MRI breast, colonoscopy, gastroscopy, renal MRI, whole-body MRI per syndrome).
- Education on early presentation; emergency / 2-week-wait access.
- Reproductive counselling — pre-implantation genetic diagnosis options.
- Lifestyle: smoking cessation, sun avoidance (especially XP, OCA), photoprotection.
References
- NHS England. Genomic Medicine Service — National Genomic Test Directory. London: NHSE; 2024.
- Garber JE, Offit K. Hereditary cancer predisposition syndromes. J Clin Oncol. 2005;23:276-292.
- Schultz KAP et al. PTEN, DICER1, FH and their associated tumor susceptibility syndromes. Clin Cancer Res. 2017;23:e76-e82.
- Carbone M et al. BAP1 cancer syndrome. Nat Rev Cancer. 2013;13:153-159.
- NICE NG14. Melanoma: assessment and management. London: NICE; 2015 (last updated 27 July 2022). NICE NG12. Suspected cancer: recognition and referral. London: NICE; 2015 (last updated 15 April 2026).
- NICE CG164. Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer. London: NICE; 2013 (last updated 14 November 2023; reviewed 11 July 2024).
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