MedGen

APC-associated polyposis conditions include (classic or attenuated) familial adenomatous polyposis (FAP) and gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). FAP is a colorectal cancer (CRC) predisposition syndrome that can manifest in either classic or attenuated form. Classic FAP is characterized by hundreds to thousands of adenomatous colonic polyps, beginning on average at age 16 years (range 7-36 years). For those with the classic form of FAP, 95% of individuals have polyps by age 35 years; CRC is inevitable without colectomy. The mean age of CRC diagnosis in untreated individuals is 39 years (range 34-43 years). The attenuated form is characterized by multiple colonic polyps (average of 30), more proximally located polyps, and a diagnosis of CRC at a later age than in classic FAP. For those with an attenuated form, there is a 70% lifetime risk of CRC and the mean age of diagnosis is 50-55 years. Extracolonic manifestations are variably present and include polyps of the stomach and duodenum, osteomas, dental abnormalities, congenital hypertrophy of the retinal pigment epithelium (CHRPE), benign cutaneous lesions, desmoid tumors, adrenal masses, and other associated cancers. GAPPS is characterized by proximal gastric polyposis, increased risk of gastric adenocarcinoma, and no duodenal or colonic involvement in most individuals reported. [from GeneReviews]

Li-Fraumeni syndrome (LFS) is a cancer predisposition syndrome associated with high risks for a diverse spectrum of childhood- and adult-onset malignancies. The lifetime risk of cancer in individuals with LFS is =70% for men and =90% for women. Five cancer types account for the majority of LFS tumors: adrenocortical carcinomas, breast cancer, central nervous system tumors, osteosarcomas, and soft-tissue sarcomas. LFS is associated with an increased risk of several additional cancers including leukemia, lymphoma, gastrointestinal cancers, cancers of head and neck, kidney, larynx, lung, skin (e.g., melanoma), ovary, pancreas, prostate, testis, and thyroid. Individuals with LFS are at increased risk for cancer in childhood and young adulthood; survivors are at increased risk for multiple primary cancers. [from GeneReviews]

Beckwith-Wiedemann syndrome (BWS) is a growth disorder variably characterized by neonatal hypoglycemia, macrosomia, macroglossia, hemihyperplasia, omphalocele, embryonal tumors (e.g., Wilms tumor, hepatoblastoma, neuroblastoma, and rhabdomyosarcoma), visceromegaly, adrenocortical cytomegaly, renal abnormalities (e.g., medullary dysplasia, nephrocalcinosis, medullary sponge kidney, and nephromegaly), and ear creases/pits. BWS is considered a clinical spectrum, in which affected individuals may have many of these features or may have only one or two clinical features. Early death may occur from complications of prematurity, hypoglycemia, cardiomyopathy, macroglossia, or tumors. However, the previously reported mortality of 20% is likely an overestimate given better recognition of the disorder along with enhanced treatment options. Macroglossia and macrosomia are generally present at birth but may have postnatal onset. Growth rate slows around age seven to eight years. Hemihyperplasia may affect segmental regions of the body or selected organs and tissues. [from GeneReviews]

Adrenocortical carcinoma (ADCC) is a rare but aggressive childhood tumor, representing about 0.4% of childhood tumors, with a high incidence of associated tumors. ADCC occurs with increased frequency in patients with the Beckwith-Wiedemann syndrome (130650) and is a component tumor in Li-Fraumeni syndrome (LFS; 151623). [from OMIM]

A malignant neoplasm of the adrenal cortex that may produce hormones such as cortisol, aldosterone, estrogen, or testosterone. [from HPO]