Table 1.
A comprehensive list of hereditary cancer syndromes. AD = autosomal dominant; AR = autosomal recessive; M = mixed; U = unknown; X = X-linked. Sources: Pubmed, Web of Science, GeneReview, UptoDate, Omim, EviQ Genetics.
| Syndrome | Acronym | Prevalence | Inheritance | Involved Genes |
|---|---|---|---|---|
| Hereditary paraganglioma-pheochromocytoma syndrome | HPPS | 1–9:1,000,000 | AD (SDHA, SDHB, SDHC, TMEM127) Paternal inheritance (SDHD, SDHAF2, MAX) |
SDHA, SDHAF2, SDHB, SDHC, SDHD, MAX, TMEM127 |
| Carney Complex | CNC | U | AD | PRKAR1A |
| Neurofibromatosis type 1 | NF1 | 1:2600 | AD | NF1 |
| Neurofibromatosis type 2 | NF2 | 1:60,000 | AD | NF2 |
| Schwannomatosis | SCHW | 1:70,000 | AD | SMARCB1, LZTR1 |
| Multiple endocrine neoplasia type 1 | MEN 1 | 1:10,000 | AD | MEN1 |
| Multiple endocrine neoplasia type 2A | MEN2A | 1:44,000 | AD | RET |
| Multiple endocrine neoplasia type 2B | MEN2B | 1:700,000 | AD | RET |
| Familial medullary thyroid carcinoma | FMTC | 1:233,000 | AD | RET |
| Multiple endocrine neoplasia type 4 | MEN4 | <1:1,000,000 | AD | CDKN1B |
| Hyperparathyroidism-jaw tumor syndrome | HPT-JT | U | AD | CDC73 |
| Parathyroid carcinoma syndrome | PC | U | AD | CDC73 |
| HOXB13 hereditary cancer syndrome | HOXB13 | U | AD | HOXB13 G84E |
| NBN hereditary cancer syndrome | NBN | U | AD (heterozygous) | NBN |
| Njimegen Breakage syndrome | NBS | 1:100,000 | AR (homozygous) | NBN |
| Von Hippel–Lindau syndrome | VHLS | 1:36,000 | AD | VHL |
| Hereditary papillary renal carcinoma syndrome | HPRC | U | AD | HPRC (MET protooncogene) |
| Hereditary leiomyomatosis and renal cancer cell syndrome | HLRCC | <1:500 | AD | FH |
| Tuberous Sclerosis Complex | TSC | 1:5800 | AD | TSC1, TSC2 |
| Birt–Hogg–Dubé syndrome | BHD | 1:500,000 | AD | FLCN |
| Li–Fraumeni syndrome | LF | 1:3500 | AD | TP53 |
| Bloom syndrome | BSyn | U | AR | BLM |
| Familial GIST | fGIST | U | AD | KIT, PDGFRA |
| BRCA1- and BRCA2-associated hereditary cancer syndrome | BRCA1/2 | 1:500 (BRCA1) 1:225 (BRCA2) |
AD | BRCA1, BRCA2 |
| CHEK2-associated hereditary cancer syndrome | CHEK2 | 1:937 (CHEK2 R95) | AD | CHEK2 |
| PALB2-associated hereditary cancer syndrome | PALB2 | 1:1250 | AD | PALB2 |
| RAD51C-associated hereditary cancer syndrome | RAD51C | 1:1600 | AD | RAD51C |
| RAD51D-associated hereditary cancer syndrome | RAD51D | U | AD | RAD51D |
| ATM-associated hereditary cancer syndrome | ATM (heterozygosis) | 1:100 | AR | ATM |
| Ataxia telangiectasia | ATM (homozygosis) | 1:40,000–300,000 | AR | ATM |
| Peutz–Jeghers syndrome | STK11 | 1:25,000–280,000 | AD | STK11 |
| BARD1-associated hereditary cancer syndrome | BARD1 | U | AD | BARD1 |
| BRIP1-associated hereditary cancer syndrome | BRIP1 | 1:500 | AD | BRIP1 |
| Fanconi Anemia | FA | 1–9:1,000,000 The carrier frequency of FA is 1/181 in the general population in North America and 1:93 in Israel. Specific populations have a founder effect with increased carrier frequencies (1 per 100 or less) |
M (AR, X) |
AR: FANCA, FANCC, FANCD1/BRCA2, FANCD2, FANCE, FANCF, FANCG (XRCC9), FANCI, FANCJ/BRIP1, FANCL, FANCM, FANCN/PALB2, FANCP/SLX4, FANCQ/ERCC4, FANCR/RAD51, FANCS/BRCA1, FANCT/UBE2T, FANCU/XRCC2, FANCV/REV7, FANCW/RFWD3, and FANCY/FAP100 X: a hemizygous pathogenic variant in FANCB |
| Familial atypical mole-malignant melanoma syndrome | FAMM | U | AD | CDKN2A, CDK4 |
| Nevoid basal cell carcinoma | NBCC | 1:31,000–164,000 | AD | PTCH1, SUFU |
| Xenoderma pigmentosus | XP | 1:1,000,000 (EU, USA), 1:22,000 (JAP) | AR | DDB2 (XPE), ERCC1, ERCC2 (XPD), ERCC3 (XPB), ERCC4 (XPF), ERCC5 (XPG), POLH (XPV), XPA, XPC |
| BAP1 tumor predisposition syndrome | BAP1 | U | AD | BAP1 |
| Shelterin complex genes hereditary cancer syndrome | Shelterin | U | AD | POT1, ACD, TERF2IP |
| TERT hereditary cancer syndrome | TERT | U | AD/AR | TERT |
| MC1R polymorphism | MC1R | U | AD | MC1R |
| MITF (E318K) polymorphism | MITF | U | AD | MITF |
| DICER1 tumor predisposition syndrome | DICER1 | U | AD | DICER1 |
| Lynch syndrome | LS | 1:279 | AD | MLH1, MSH2, MSH6, PMS2, EPCAM |
| RPS20-associated hereditary nonpolyposis colorectal cancer syndrome | RPS20 | U | AD | RPS20 |
| Familial adenomatous polyposis | FAP | 1:8000 | AD | APC |
| Attenuated familial adenomatous polyposis | AFAP | U | AD | APC |
| Gastric adenocarcinoma and proximal polyposis of the stomach | GAPPS | U | AD | APC |
| Polymerase proofreading-associated polyposis | PPAP | U | AD | POLE, POLD1 |
| MUTYH-associated polyposis | MAP | 1:20,000 (carrier 1:100) |
AR | MUTYH |
| NTHL1 tumor syndrome | NTHL1 | U | AR | NTHL1 |
| MSH3-associated polyposis | MSH3 | <1:1,000,000 | AR | MSH3 |
| MLH3-associated polyposis | MLH3 | U | AR | MLH3 |
| Juvenile polyposis syndrome | JPS | U | AD | BMPR1A, SMAD4 |
| Hereditary mixed polyposis syndrome | HMPS | U | AD | GREM1 |
| Sessile serrated polyposis cancer syndrome | RNF43 | U | AD | RNF43 |
| Cowden syndrome | CS | 1:200,000 | AD | PTEN |
| Hereditary diffuse gastric cancer syndrome | HDGC | U | AD | CDH1 |
| Hereditary pancreatitis | HP | 1–9:1,000,000 | AD (PRSS1, CFTR, SPINK1, CPA1, CTRC, CASR, CEL) X (CLDN2) AR (CFTR, SPINK1, TRPV6) |
PRSS1, SPINK1, CFTR, CTRC, CLDN2, CPA1 (Putative genes: CEL, CELP, CASR, GGT1, TRPV6) |
| Howel–Evans syndrome | HE | <1:1,000,000 | AD | RHBDF2 |
| EGFR-associated genetic susceptibility | EGFR | U | AD | EGFR |