Syndromes

Question 1

MEN1

Answer 1

Gene: MEN1
Features: 3Ps - pit adenoma, parathyroid hyperplasia, pancreatic/duodenal NETs

Question 2

MEN2A

Answer 2

Gene: RET
Features: 1M 2Ps - Medullary thyroid CA, Parathyroid hyperplasia, pheo

Question 3

MEN2B

Answer 3

Gene: RET
Features: 2M 1P - Medullary thyroid CA, Marfanoid habitus, pheo, diffuse ganglioneuromatosis of GI tract

Question 4

MEN4

Answer 4

Gene: CDKN1B
Features: same as MEN1

Question 5

NF1

Answer 5

Gene: NF1 (neurofibromin)
Features: Multiple neurofibromas, optic nerve pilocytic astro, GIST, cafe-au-lait spots, lisch nodules

Question 6

NF2

Answer 6

Gene: NF2 (merlin)
Features: Bilateral acoustic schwannomas, meningiomas, ependymomas, cafe-au-lait spots but NO lisch nodules

Question 7

Tuberous Sclerosis

Answer 7

Gene: TSC1 (hamartin), TSC2 (tuberin)
Features: PEComas (renal angiomyolipoma, pulmonary lymphangiomeiomyomatosis, clear cell sugar tumor of lung etc), cardiac rhabdomyoma, cortical tubers, supependymal giant cell astrocytoma, cutaneous angiofibromas, eosinophilic solid and cystic RCC

Question 8

Sturge-Weber

Answer 8

Gene: GNAQ
Features: Port-wine stain in trigeminal nerve distribution, Angiomatosis of leptomeninges, pheo, choroidal hemangioma

Question 9

VHL

Answer 9

Gene: VHL (pVHL)
Features: CCRCC, cysts (kidney, pancreas, liver), hemangioblastomas, pheo, papillary cystadenoma of epididymis/broad ligament, endolymphatic sac tumor of ear

Question 10

Birt-Hogg-Dube

Answer 10

Gene: BHD (folliculin)
Features: RCC, oncocytoma, hybrid oncocytic tumor (highly specific), facial fibrofolliculomas, pulmonary cysts with spontaneous pneumothorax

Question 11

Beckwith-Wiedeman

Answer 11

Gene: Duplication of paternal allele 11p15
Features: Overgrowth of organs, tongue, childhood neoplasia (nephroblastoma, pancreatoblastoma, hepatoblastoma, neuroblastoma)

Question 12

WAGR

Answer 12

Gene: Deletion of WT1
Features: Wilms tumor, aniridia, GU abnormalities, mental retardation

Question 13

Denys-Drash

Answer 13

Gene: WT1 point mutation
Features: Wilms tumor, gonadoblastoma, diffuse mesangial sclerosis

Question 14

Hereditary papillary renal cell cancer

Answer 14

Gene: MET
Features: Multiple bilateral papillary RCC

Question 15

Hereditary leiomyomatosis and renal cell carcinoma

Answer 15

Gene: FH/fumarate hydratase
Features: RCCs and leiomyomas (cutaneous and uterine) with notable nuclear abnormalities

Question 16

Succinate dehydrogenase-deficient RCC

Answer 16

Gene: SDHB&raquo_space; SDHC» SDHD > SDHA
Features: RCCs with notable features, pheo/paraganglioma, GIST

Question 17

McCune-Albright

Answer 17

Gene: Mosaicism in GNAS1
Features: Fibrous dysplasia (polyostatic), cafe-au-lait spots, endocrine abnormalities

Question 18

Mazabrand syndrome

Answer 18

Gene: Activating GNAS1
Features: Fibrous dysplasia, soft tissue myxoma

Question 19

Ollier disease

Answer 19

Gene: IDH1/2
Features: Enchondromatosis, increased risk of chondrosarc

Question 20

Maffucci syndrome

Answer 20

Gene: IDH1/2
Features: Enchondromatosis, soft tissue hemangiomas, increased risk of chondrosarc and angiosarc

Question 21

FAP

Answer 21

Gene: APC
Features: Colonic polyposis and carcinoma, small intestine (particularly duodenum and periampullary) polyps, periampullary adenoCA, fundic gland polyps (esp with dysplasia), cribriform-morular variant PTC, nasal angiofibromas

Question 22

Gardner syndrome

Answer 22

Gene: APC
Features: FAP features PLUS fibromatosis, osteomas, nuchal fibromas, epidermoid cysts, pilomatricomas, unerupted and supernumerary teeth, CHRPE (congenital hypertrophy of the retinal pigment epithelium)

Question 23

Turcot syndrome

Answer 23

Gene: APMS2
Features: FAP features PLUS Medulloblastoma
OR
glioblastoma and Lynch syndrome tumors

Question 24

Hereditary nonpolyposis colorectal cancer/Lynch syndrome

Answer 24

Gene: MLH1, MSH2, MSH6, PMS2, EPCAM
Features: Colorectal CA, endometrial CA, ovarian CA, gastric, pancreatobiliary, urothelial CA of upper urinary tract, small bowel, brain, sebaceous neoplasms

Question 25

Muir-Torre

Answer 25

Gene: MSH2 Features: Lynch tumors, sebaceous neoplasms, keratoacanthoma

Question 26

MYH-associated polyposis

Answer 26

Gene: MYH Features: Attenuated FAP but AR inheritance pattern

Question 27

Hereditary diffuse gastric cancer syndrome

Answer 27

Gene: CDH1 (E-cadherin) Features: gastric signet ring cell CA, lobular breast CA

Question 28

Peutz-Jeghers syndrome

Answer 28

Gene: STK11 Features: hamartomatous GI polyps (small bowel >> stomach, colon), colorectal CA, pancreatic CA, gastric CA, small bowel CA,, cervical minimal deviation adenocarcinoma, sex cord tumor with annual tubules (SCTAT), large cell calcifying Sertoli cell tumor, Breast CA, lung CA

Question 29

Juvenile Polyposis

Answer 29

Gene: SMAD4 Features: Juvenile polyp involving colon or entire GI tract. Associated CRC risk

Question 30

Cronkhite-Canada

Answer 30

Gene: Unknown, not familial Features: Stomach, small bowel, colon hyperplastic-type polyps. Minimally increased CRC risk Alopecia, cutaneous macular hyperpigmentation

Question 31

Hereditary Breast and Ovarian Cancer

Answer 31

Gene: BRCA1 Features: Breast cancer (esp medullary, triple neg), serous ovarian carcinoma Gene: BRCA2 Features: Breast CA (Luminal type), ovarian CA, male breast CA, prostate CA, pancreatic

Question 32

Cowden Disease

Answer 32

Gene: PTEN Features: Breast CA. trichilemmomas, hamartomatous/hyperplasia/adenomatous/inflammatory GI polyps, hemangiomas, lymphangiomas, thyroid, RCC, Merkle, melanoma

Question 33

Familial atypical multiple mole melanoma syndrome

Answer 33

Gene: CDKN2A Features: dysplasia nevi, melanoma, pancreatic adenocarcinoma

Question 34

Gorlin syndrome

Answer 34

Gene: PTCH1 Features: BCCs, OKCs, bilateral ovarian fibroma, medulloblastoma, congenital malformations

Question 35

Xeroderma Pigmentosa

Answer 35

Gene: XP family Features: BCC, SCC, keratoacanthoma, melanoma, progressive neurologic deterioration

Question 36

Mahvash disease

Answer 36

Gene: GCGR - autosomal recessive inheritance Features: pancreatic islet glucagon cell hyperplasia, micro and macroglucagonomas

Question 37

Hyperparathyroidism-jaw tumor syndrome

Answer 37

Gene: CDC73 Features: Parathyroid carcinoma, ossifying fibromas of jaw

Question 38

Carney-Stratakis syndrome

Answer 38

Gene: SDHB >> SDHC>> SDHD > SDHA Features: pheo/paraganaglioma, GISTs (esp epithelioid), SDH-deficient RCC, PitNET

Question 39

Carney triad

Answer 39

Gene: SDHC promoter hypermethylation Features: pheo/paraganglioma, GIST (esp epithelioid), pulmonary chondroma

Question 40

Li-Fraumeni

Answer 40

Gene: TP53 (p53) Features: Sarcomas, carcinoma (breast, colon, pancreas, adrenal), leukemia, melanoma, glioma

Question 41

Ataxia-Telangiectasia

Answer 41

Gene: ATM - autosomal recessive inheritance Features: leukemias/lymphomas, carcinomas (breast, gastric, liver), variable immunodeficiency

Question 42

Bloom syndrome

Answer 42

Gene: BLM - autosomal recessive Features: wide range of malignancy esp leukemias

Question 43

Fanconi anemia

Answer 43

Gene: unspecified Features: Leukemias, HCC, BM hypoplasia

Question 44

Carney Complex

Answer 44

Gene: PRKAR1A Features: Myxomas, pigmented and calcifying lesions (blue nevus, pigmented nodular adrenocortical hyperplasia, psammomatous melanotic schwannoma), endocrine hyperactivity

Question 45

Retinoblastoma

Answer 45

Gene: RB1 Features: Bilateral retinoblastoma, pineoblastoma, osteosarcoma

Question 46

Hereditary hemorrhagic telangiectasia

Answer 46

Gene: ACVRL Features: Aneurysmal telangiectasia of multiple organs complicated by bleeding

Question 47

DICER1 syndrome

Answer 47

Gene: DICER1 Features: Pleuropulmonary blastoma, cystic nephroma, sertoli-leydig cell tumor of ovary, chondromesenchymal hamartoma

Question 48

BAP1 hereditary cancer predisposition syndrom

Answer 48

Gene: BAP1 Features: Uveal and cutaneous melanoma, BAP-1 associated nevi, mesothelioma, CCRCC

Question 49

Rhabdoid tumor predisposition syndrome

Answer 49

Gene: SMARCB1 Features: Malignant rhabdoid tumor (renal and extrarenal), ATRT, SCCOHT