Multiple endocrine neoplasia is a condition which encompasses several distinct syndromes featuring tumors of endocrine glands, each with its own characteristic pattern. In some cases, the tumors are malignant, in others, benign. Benign or malignant tumors of nonendocrine tissues occur as components of some of these tumor syndromes.
Proteus syndrome is a rare disorder with a genetic background that can cause tissue overgrowth involving all three embryonic lineages. Patients with Proteus syndrome tend to have an increased risk of embryonic tumor development. The clinical and radiographic symptoms of Proteus syndrome are highly variable, as are its orthopedic manifestations.
Li–Fraumeni syndrome is a rare, autosomal dominant, hereditary disorder that predisposes carriers to cancer development. It was named after two American physicians, Frederick Pei Li and Joseph F. Fraumeni Jr., who first recognized the syndrome after reviewing the medical records and death certificates of 648 childhood rhabdomyosarcoma patients. This syndrome is also known as the sarcoma, breast, leukaemia and adrenal gland (SBLA) syndrome.
Hereditary nonpolyposis colorectal cancer (HNPCC) is a hereditary predisposition to colon cancer.
A benign tumor is a mass of cells (tumor) that does not invade neighboring tissue or metastasize. Compared to malignant (cancerous) tumors, benign tumors generally have a slower growth rate. Benign tumors have relatively well differentiated cells. They are often surrounded by an outer surface or stay contained within the epithelium. Common examples of benign tumors include moles and uterine fibroids.
Succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial (CybS), also known as succinate dehydrogenase complex subunit D (SDHD), is a protein that in humans is encoded by the SDHD gene. Names previously used for SDHD were PGL and PGL1. Succinate dehydrogenase is an important enzyme in both the citric acid cycle and the electron transport chain. Hereditary PGL-PCC syndrome is caused by a parental imprint of the SDHD gene. Screening can begin by 6 years of age.
Birt–Hogg–Dubé syndrome (BHD), also Hornstein–Birt–Hogg–Dubé syndrome, Hornstein–Knickenberg syndrome, and fibrofolliculomas with trichodiscomas and acrochordons is a human, adult onset, autosomal dominant genetic disorder caused by a mutation in the folliculin (FLCN) gene. It can cause susceptibility to kidney cancer, renal and pulmonary cysts, and noncancerous tumors of the hair follicles, called fibrofolliculomas. The symptoms seen in each family are unique, and can include any combination of the three symptoms. Fibrofolliculomas are the most common manifestation, found on the face and upper trunk in over 80% of people with BHD over the age of 40. Pulmonary cysts are equally common (84%) and 24% of people with BHD eventually experience a collapsed lung. Kidney tumors, both cancerous and benign, occur in 14–34% of people with BHD; the associated kidney cancers are often rare hybrid tumors.
A hamartoma is a mostly benign, local malformation of cells that resembles a neoplasm of local tissue but is usually due to an overgrowth of multiple aberrant cells, with a basis in a systemic genetic condition, rather than a growth descended from a single mutated cell (monoclonality), as would typically define a benign neoplasm/tumor. Despite this, many hamartomas are found to have clonal chromosomal aberrations that are acquired through somatic mutations, and on this basis the term hamartoma is sometimes considered synonymous with neoplasm. Hamartomas are by definition benign, slow-growing or self-limiting, though the underlying condition may still predispose the individual towards malignancies.
Phosphatase and tensin homolog (PTEN) is a phosphatase in humans and is encoded by the PTEN gene. Mutations of this gene are a step in the development of many cancers, specifically glioblastoma, lung cancer, breast cancer, and prostate cancer. Genes corresponding to PTEN (orthologs) have been identified in most mammals for which complete genome data are available.
Carney complex and its subsets LAMB syndrome and NAME syndrome are autosomal dominant conditions comprising myxomas of the heart and skin, hyperpigmentation of the skin (lentiginosis), and endocrine overactivity. It is distinct from Carney's triad. Approximately 7% of all cardiac myxomas are associated with Carney complex.
Bannayan–Riley–Ruvalcaba syndrome (BRRS) is a rare overgrowth syndrome and hamartomatous disorder with occurrence of multiple subcutaneous lipomas, macrocephaly and hemangiomas. The disease is inherited in an autosomal dominant manner. The disease belongs to a family of hamartomatous polyposis syndromes, which also includes Peutz–Jeghers syndrome, juvenile polyposis and Cowden syndrome. Mutation of the PTEN gene underlies this syndrome, as well as Cowden syndrome, Proteus syndrome, and Proteus-like syndrome, these four syndromes are referred to as PTEN Hamartoma-Tumor Syndromes.
Endometrial intraepithelial neoplasia (EIN) is a premalignant lesion of the uterine lining that predisposes to endometrioid endometrial adenocarcinoma. It is composed of a collection of abnormal endometrial cells, arising from the glands that line the uterus, which have a tendency over time to progress to the most common form of uterine cancer—endometrial adenocarcinoma, endometrioid type.
Juvenile polyposis syndrome is an autosomal dominant genetic condition characterized by the appearance of multiple juvenile polyps in the gastrointestinal tract. Polyps are abnormal growths arising from a mucous membrane. These usually begin appearing before age 20, but the term juvenile refers to the type of polyp, not to the age of the affected person. While the majority of the polyps found in juvenile polyposis syndrome are non-neoplastic, hamartomatous, self-limiting and benign, there is an increased risk of adenocarcinoma.
Muir–Torre syndrome is a rare hereditary, autosomal dominant cancer syndrome that is thought to be a subtype of HNPCC. Individuals are prone to develop cancers of the colon, genitourinary tract, and skin lesions, such as keratoacanthomas and sebaceous tumors. The genes affected are MLH1, MSH2, and more recently, MSH6, and are involved in DNA mismatch repair.
Hereditary breast–ovarian cancer syndromes (HBOC) are cancer syndromes that produce higher than normal levels of breast cancer, ovarian cancer and additional cancers in genetically related families. It accounts for 90% of the hereditary cancers. The hereditary factors may be proven or suspected to cause the pattern of breast and ovarian cancer occurrences in the family. The name HBOC may be misleading because it implies that this genetic susceptibility to cancer is mainly in women. In reality, both sexes have the same rates of gene mutations and HBOC can predispose to other cancers including prostate cancer and pancreatic cancer. For this reason, the term "King syndrome" has recently come into use. The new name references Mary-Claire King who identified the genes BRCA1 and BRCA2.
Lhermitte–Duclos disease (LDD), also called dysplastic gangliocytoma of the cerebellum (DGC), is a rare, slowly growing tumor of the cerebellum, a gangliocytoma sometimes considered to be a hamartoma, characterized by diffuse hypertrophy of the granular layer of the cerebellum. It is often associated with Cowden syndrome. It was described by Jacques Jean Lhermitte and P. Duclos in 1920.
Perlman syndrome (PS), also known as nephroblastomatosis-fetal ascites-macrosomia-Wilms tumor syndrome, is a rare overgrowth syndrome caused by autosomal recessive mutations in the DIS3L2 gene. PS is characterized by macrocephaly, neonatal macrosomia, nephromegaly, renal dysplasia, dysmorphic facial features, and increased risk for Wilms' tumor. The syndrome is associated with high neonatal mortality.
A hereditary cancer syndrome is a genetic disorder in which inherited genetic mutations in one or more genes predispose the affected individuals to the development of cancer and may also cause early onset of these cancers. Hereditary cancer syndromes often show not only a high lifetime risk of developing cancer, but also the development of multiple independent primary tumors.
Charis Eng is a Singapore-born physician-scientist and geneticist at the Cleveland Clinic, notable for identifying the PTEN gene. She is the Chairwoman and founding Director of the Genomic Medicine Institute of the Cleveland Clinic, founding Director and attending clinical cancer geneticist of the institute’s clinical component, the Center for Personalized Genetic Healthcare, and Professor and Vice Chairwoman of the Department of Genetics and Genome Sciences at Case Western Reserve University School of Medicine.
Hereditary lobular breast cancer is a rare inherited cancer predisposition associated with pathogenic CDH1 (gene) germline mutations, and without apparent correlation with the hereditary diffuse gastric cancer syndrome. Research studies identified novel CDH1 germline variants in women with diagnosed lobular breast cancer and without any family history of gastric carcinoma. Firstly, in 2018 Giovanni Corso et al. defined this syndrome as a new cancer predisposition and the Authors suggested additional clinical criteria to testing CDH1 in lobular breast cancer patients. In 2020, the International Gastric Cancer Linkage Consortium recognized officially that the hereditary lobular breast cancer is a possible independent syndrome. To date, there are reported about 40 families clustering for lobular breast cancer and associated with CDH1 germline mutations but without association with diffuse gastric cancer. Other recent studies demonstrated a possible correlation between hereditary lobular breast cancer and gastric cancer risk.
