1Fanconi anemia
Gene/chromosome: FANCA (16q), multiple Fanconi genes; Inheritance: Usually autosomal recessive; Triad: Pancytopenia, congenital anomalies, short stature; Associated: AML, MDS, squamous cell carcinoma; Investigation: Chromosomal breakage test with diepoxybutane (DEB) or mitomycin C
2Bloom syndrome
Gene/chromosome: BLM, chromosome 15; Inheritance: Autosomal recessive; Triad: Short stature, photosensitive facial erythema, recurrent infections; Associated: Leukemia, lymphoma, multiple solid tumors; Investigation: Increased sister chromatid exchanges
3Li-Fraumeni syndrome
Gene/chromosome: TP53, chromosome 17; Inheritance: Autosomal dominant; Triad: Early-onset cancers, sarcomas, breast cancer; Associated: Osteosarcoma, brain tumors, adrenocortical carcinoma, breast cancer; Investigation: Germline TP53 testing
4Lynch syndrome
Gene/chromosome: MLH1, MSH2, MSH6, PMS2, EPCAM; Inheritance: Autosomal dominant; Triad: Early colorectal cancer, endometrial cancer, family history of related cancers; Associated: Colorectal, endometrial, ovarian, gastric, urinary tract cancers; Investigation: Tumor MSI testing or mismatch-repair immunohistochemistry
5Familial adenomatous polyposis (FAP)
Gene/chromosome: APC, chromosome 5; Inheritance: Autosomal dominant; Triad: Hundreds of colorectal adenomas, early colorectal cancer, family history; Associated: Colorectal carcinoma, desmoid tumors, osteomas; Investigation: Colonoscopy and APC genetic testing
6Gardner syndrome
Gene/chromosome: APC, chromosome 5; Inheritance: Autosomal dominant; Triad: Colonic polyposis, osteomas, dental abnormalities; Associated: Colorectal carcinoma, desmoid tumors; Investigation: Colonoscopy, APC testing
7Peutz-Jeghers syndrome
Gene/chromosome: STK11, chromosome 19; Inheritance: Autosomal dominant; Triad: Hamartomatous polyps, mucocutaneous pigmentation, intussusception; Associated: Pancreatic, breast, ovarian, gastrointestinal cancers; Investigation: STK11 testing, endoscopy
8Cowden syndrome
Gene/chromosome: PTEN, chromosome 10; Inheritance: Autosomal dominant; Triad: Multiple hamartomas, macrocephaly, mucocutaneous lesions; Associated: Breast, thyroid, endometrial cancers; Investigation: PTEN genetic testing
9Hereditary retinoblastoma
Gene/chromosome: RB1, chromosome 13; Inheritance: Autosomal dominant predisposition; Triad: Bilateral retinoblastoma, leukocoria, early-onset tumor; Associated: Osteosarcoma, pineal tumors, second malignancies; Investigation: RB1 testing, fundus examination
10Hereditary breast and ovarian cancer syndrome
Gene/chromosome: BRCA1 chromosome 17, BRCA2 chromosome 13; Inheritance: Autosomal dominant; Triad: Early breast cancer, ovarian cancer, family history; Associated: Breast, ovarian, prostate, pancreatic cancers; Investigation: Germline BRCA testing
11MEN 1 syndrome
Gene/chromosome: MEN1, chromosome 11; Inheritance: Autosomal dominant; Triad: Parathyroid, pancreatic/duodenal neuroendocrine, pituitary tumors; Associated: Gastrinoma, insulinoma, prolactinoma; Investigation: MEN1 genetic testing, calcium/PTH, hormone evaluation
12MEN 2A syndrome
Gene/chromosome: RET, chromosome 10; Inheritance: Autosomal dominant; Triad: Medullary thyroid carcinoma, pheochromocytoma, hyperparathyroidism; Associated: Medullary thyroid carcinoma; Investigation: RET testing, serum calcitonin, metanephrines
13MEN 2B syndrome
Gene/chromosome: RET, chromosome 10; Inheritance: Autosomal dominant; Triad: Medullary thyroid carcinoma, pheochromocytoma, mucosal neuromas; Associated: Marfanoid habitus, intestinal ganglioneuromatosis; Investigation: RET testing, serum calcitonin
14Birt-Hogg-Dubé syndrome
Gene/chromosome: FLCN, chromosome 17; Inheritance: Autosomal dominant; Triad: Fibrofolliculomas, lung cysts, spontaneous pneumothorax; Associated: Renal cell carcinoma; Investigation: FLCN testing, renal MRI
15Hereditary diffuse gastric cancer
Gene/chromosome: CDH1, chromosome 16; Inheritance: Autosomal dominant; Triad: Diffuse gastric cancer, signet-ring histology, family history; Associated: Lobular breast carcinoma; Investigation: CDH1 testing, upper GI surveillance
16Hereditary spherocytosis
Gene/chromosome: ANK1, SPTB, SPTA1, SLC4A1, EPB42; Inheritance: Usually autosomal dominant; Triad: Anemia, jaundice, splenomegaly; Associated: Pigment gallstones, aplastic crisis with parvovirus B19; Investigation: Increased EMA binding test, spherocytes on smear
17Thalassemia major
Gene/chromosome: HBB, chromosome 11; Inheritance: Autosomal recessive; Triad: Severe anemia, hepatosplenomegaly, growth failure; Associated: Iron overload, cardiomyopathy, endocrine dysfunction; Investigation: Hb electrophoresis/HPLC showing increased HbF and HbA2 pattern
18Sickle cell disease
Gene/chromosome: HBB, chromosome 11; Inheritance: Autosomal recessive; Triad: Hemolytic anemia, vaso-occlusive pain, functional asplenia; Associated: Acute chest syndrome, stroke, osteomyelitis; Investigation: Hb electrophoresis showing HbS
19G6PD deficiency
Gene/chromosome: G6PD, chromosome X; Inheritance: X-linked; Triad: Episodic hemolysis, jaundice, dark urine; Associated: Hemolysis after oxidant drugs, fava beans, infection; Investigation: G6PD enzyme assay