Mismatch repair cancer syndrome (MMRCS) is a cancer syndrome associated with biallelic DNA mismatch repair mutations. It is also known as Turcot syndrome (after Jacques Turcot, who described the condition in 1959) and by several other names.

In MMRCS, neoplasia typically occurs in both the gut and the central nervous system (CNS). In the large intestine, familial adenomatous polyposis occurs; in the CNS, brain tumors.

The classical LFS malignancies - sarcoma, cancers of the breast, brain and adrenal glands - comprise about 80% of all cancers that occur in this syndrome.

The risk of developing any invasive cancer (excluding skin cancer) is ~50% by age 30 (1% in the general population) and is 90% by age 70. Early onset breast cancer accounts for 25% of all the cancers in this syndrome. This is followed by soft tissue sarcomas (20%), bone sarcoma (15%) and brain tumors - especially glioblastomas - (13%). Other tumours seen in this syndrome include leukemia, lymphoma and adrenocortical carcinoma.

~90% of females with LFS develop breast cancer by age 60 years; the majority of these occur before age 45 years. Females with this syndrome have almost a 100% lifetime risk of developing cancer. This compares with 73% for affected males. The difference may be due to much smaller breast tissue in males as well as increased estrogen levels in females.

The risks of sarcoma, female breast cancer and haematopoietic malignancies in mutation carriers are more than 100 times greater than those seen in the general population.

Other tumours reported in this syndrome but not yet proved to be linked with it include melanoma, Wilm's and other kidney tumors, hepatacellular carcinoma, gonadal germ cell, pancreatic, gastric, choroid plexus, colorectal and prostate cancers.

80% of children with adrenocortical carcinoma and 2%-10% of childhood brain tumors have p53 mutations.

2%-3% of osteosarcomas, 9% rhabdomyosarcomas and 7%-20% patients with multiple primary tumors have p53 mutations.

Although most cases of this syndrome have early onset of cancer, cases have also been reported later in life.

Muir–Torre syndrome (MTS) 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.

Muir–Torre syndrome is characterized by both:

1. At least a single sebaceous gland tumor (either an adenoma, an epithelioma, or a carcinoma)

2. A minimum of one internal malignancy

The Amsterdam criteria are frequently used to diagnose Lynch syndrome and Muir–Torre syndrome. They include the following:

- 3 or more relatives with an HNPCC-associated cancer (i.e., colorectal, cancer of the endometrium, small bowel, ureter, or renal pelvis)

- 2 or more successive generations affected by cancer

- 1 or more persons with cancer is a first-degree relative of the other 2, at least 1 case of colorectal cancer younger than age 50 years, a diagnosis of familial adenomatous polyposis has been excluded, tumors are verified by histologic examination

Muir–Torre syndrome is a genetic condition. Mutations in MLH1 and MSH2 are linked with the disease. These genes code for DNA mismatch repair genes, and mutations increase the risk of developing cancerous qualities.

Many patients who have sebaceous neoplasms with mutations in MSH2 and MLH1 do not in fact have Muir–Torre syndrome. The Mayo Muir–Torre risk score was devised to improve the positive predictive value of immunohistochemistry and reduce the false positive rate.

The Mayo Muir–Torre Risk score assigns points based several characteristics. A score of 2 or greater has a high positive predictive value of Muir–Torre syndrome. A score of 1 or lower is less likely to be Muir–Torre syndrome.

Age of onset of first sebaceous neoplasm: <60 years = 1 point, otherwise 0 points

Total number of sebaceous neoplasms: 1 = 0 points, >2 = 2 points.

Personal history of Lynch related cancers: No = 0 points, Yes = 1 point

Family history of Lynch-related cancer: No = 0 points, Yes = 1 point

The most common internal malignancies associated with Muir–Torre syndrome are: Colorectal (56%), Urogenital (22%), Small Intestine (4%), and Breast (4%). A variety of other internal malignancies have been reported.

Bannayan–Riley–Ruvalcaba syndrome is associated with enlarged head and benign mesodermal hamartomas (multiple hemangiomas, and intestinal polyps). Dysmorphy as well as delayed neuropsychomotor development can also be present. The head enlargement does not cause widening of the ventricles or raised intracranial pressure; these individuals have a higher risk of developing tumors, as the gene involved in BRRs is phosphatase and tensin homologue.

Some individuals have thyroid issues consistent with multinodular goiter, thyroid adenoma, differentiated non-medullary thyroid cancer,

most lesions are slowly growing. Visceral as well as intracranial involvement may occur in some cases, and can cause bleeding and symptomatic mechanical compression

A cancer syndrome or family cancer syndrome is a genetic disorder in which inherited genetic mutations in one or more genes predispose the affected individuals to the development of cancers and may also cause the early onset of these cancers. Cancer syndromes often show not only a high lifetime risk of developing cancer, but also the development of multiple independent primary tumors. Many of these syndromes are caused by mutations in tumor suppressor genes, genes that are involved in protecting the cell from turning cancerous. Other genes that may be affected are DNA repair genes, oncogenes and genes involved in the production of blood vessels (angiogenesis). Common examples of inherited cancer syndromes are hereditary breast-ovarian cancer syndrome and hereditary non-polyposis colon cancer (Lynch syndrome).

Li–Fraumeni syndrome is diagnosed if the following three criteria are met:

- the patient has been diagnosed with a sarcoma at a young age (below 45),

- a first-degree relative has been diagnosed with any cancer at a young age (below 45), and

- another first-degree or a second-degree relative has been diagnosed with any cancer at a young age (below 45) or with a sarcoma at any age.

Other criteria have also been proposed:

- a proband with any childhood cancer or sarcoma, brain tumor or adrenal cortical carcinoma diagnosed before age 45

- a first or second degree relative with a typical LFS malignancy (sarcoma, leukaemia, or cancers of the breast, brain or adrenal cortex) regardless of age at diagnosis

and/or

- a first or second degree relative with any cancer diagnosed before age 60.

A third criterion has been proposed

- two first or second degree relatives with LFS-related malignancies at any age.

People with Cowden syndrome develop characteristic lesions called hamartomas, which are small, noncancerous growths that are most commonly found on the skin and mucous membranes (such as the lining of the mouth, nose, and intestines), but can also occur other parts of the body, such as the thyroid and breast. The majority of affected individuals develop the characteristic skin lesions by 20 years of age.

Hamartomas are typically benign; however, people with Cowden syndrome are at increased risk of developing several types of cancer, including cancers of the breast, thyroid, uterus (endometrial), and kidney cancers. Two thirds of people have thyroid abnormalities, which usually consist of follicular adenomas (benign) or multinodular goiter of the thyroid. Up to 10 percent of people with Cowden Syndrome develop follicular thyroid cancer.

Skin abnormalities in people with Cowdens syndrome can include oral and skin papillomas and benign growths of the skin called trichilemmomas. Additional signs and symptoms of Cowden syndrome can include an enlarged head (macrocephaly), a rare noncancerous brain tumor called Lhermitte-Duclos disease, and glycogenic acanthosis of the esophagus. Up to 75% have benign breast conditions such as ductal hyperplasia, intraductal papillomatosis, adenosis, lobular atrophy, fibroadenomas, and fibrocystic changes.

Gardner syndrome, also known as Gardner's syndrome or familial colorectal polyposis, is an autosomal dominant form of polyposis characterized by the presence of multiple polyps in the colon together with tumors outside the colon. The extracolonic tumors may include osteomas of the skull, thyroid cancer, epidermoid cysts, fibromas, as well as the occurrence of desmoid tumors in approximately 15% of affected individuals.

Desmoid tumors are fibrous tumors which usually occur in the tissue covering the intestines and may be provoked by surgery to remove the colon. The countless polyps in the colon predispose to the development of colon cancer; if the colon is not removed, the chance of colon cancer is considered to be very significant. Polyps may also grow in the stomach, duodenum, spleen, kidneys, liver, mesentery and small bowel. In a small number of cases, polyps have also appeared in the cerebellum. Cancers related to Gardner syndrome commonly appear in the thyroid, liver and kidneys. The number of polyps increases with age, and hundreds to thousands of polyps can develop in the colon.

The syndrome was first described in 1951. There is no cure at this time, and in its more advanced forms, it is considered a terminal diagnosis with a life expectancy of 35–45 years; treatments are surgery and palliative care, although some chemotherapy has been tried with limited success.

Cowden syndrome (also known as Cowden's disease and sometimes as multiple hamartoma syndrome) is a rare autosomal dominant inherited disorder characterized by multiple non-cancerous tumor-like growths called hamartomas, which typically are found in the skin, mucous membranes (mouth, nasal membranes, GI tract), thyroid gland, and breast tissue. While the hamartomas are benign, people with Cowden syndrome are at increased risk of certain forms of cancer, including breast, thyroid, uterus (endometrial), and kidney cancers.

Cowden syndrome is associated with mutations in PTEN, a tumor suppressor gene, that cause the PTEN protein not to work properly leading to hyperactivity of the mTOR pathway. These mutations lead to characteristic features including macrocephaly, intestinal hamartomatous polyps, benign skin tumors (multiple trichilemmomas, papillomatous papules, and acral keratoses) and dysplastic gangliocytoma of the cerebellum (Lhermitte-Duclos disease). In addition, there is a predisposition to breast carcinoma, follicular carcinoma of the thyroid, and endometrial carcinoma.

Birt–Hogg–Dubé syndrome affects the skin and increases the risk of tumors in the kidneys and lungs. The condition is characterized by multiple noncancerous dome-shaped tumors of the hair follicles (fibrofolliculomas), particularly on the face, neck, and—more rarely—the upper chest. The fibrofolliculomas are generally described as having an opaque white color or a yellowish tone and have a waxy, smooth texture. The tumors are always found on and around the nose and on and behind the outer ear. Typically, they first appear in a person's 20s or 30s, and are found in more than 80% of people with the syndrome above the age of 40. The tumors become larger and more numerous over time. Tumors differ between individuals: they may appear merged in plaques, look similar to a comedo with a plug of keratin, or include epidermoid cysts. A large number of tumors on the face can be associated with hyperseborrhea (abnormally elevated sebum production). The presence of fibrofolliculomas on a person's face can cause significant psychological distress.

Other tumors can include trichodiscomas (tumors of the hair disc, which may be identical to fibrofolliculomas), angiofibromas, and perifollicular fibromas. However, angiofibromas are more common in tuberous sclerosis. Along with the tumors, other skin conditions are seen in people with Birt–Hogg–Dubé syndrome. Approximately 40% of people or families with the disease have papules in their mouth, which can be located on the cheeks (buccal mucosa), tongue, gums, or lips. Either white or mucosa-colored, they are discrete, small, and soft and consist of fibrous tissue covered in thickened epithelium. Collagenomas of the skin are also found in some families. Many people with BHD have skin lesions that appear to be acrochordons (skin tags), but may instead be fibrofolliculomas. These lesions are usually found in the armpit, on the eyelids, and in folds of skin. Not all individuals develop the facial tumors; some families with the mutation that causes BHD develop only kidney tumors or spontaneous pneumothorax.

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.

The risks associated with this syndrome include a strong tendency of developing cancer in a number of parts of the body. While the hamartomatous polyps themselves only have a small malignant potential (<3% - OHCM), patients with the syndrome have an increased risk of developing carcinomas of the pancreas, liver, lungs, breast, ovaries, uterus, testicles and other organs.

The average age of first diagnosis is 23, but the lesions can be identified at birth by an astute pediatrician or family physician. Prior to puberty, the mucocutaneous lesions can be found on the palms and soles. Often the first presentation is a bowel obstruction from an intussusception which is a common cause of mortality; an intussusception is a telescoping of one loop of bowel into another segment.

People over 20 years of age with Birt–Hogg–Dubé syndrome have an increased risk of developing slow-growing kidney tumors (chromophobe renal carcinoma and renal oncocytoma, respectively), kidney cysts, and possibly tumors in other organs and tissues. These tumors often occur in both kidneys and in multiple locations in each kidney. The average number of kidney tumors found in a person with BHD is 5.3, though up to 28 tumors have been found. Hybrid oncocytoma/chromophobe carcinoma, found in 50% of cases, is the most commonly found cancer, followed by chromophobe renal carcinoma, clear cell renal carcinoma, renal oncocytoma, and papillary renal cell carcinoma. People over 40 years old and men are more likely to develop kidney tumors, which are diagnosed at a median age of 48. Kidney cancer associated with BHD have been diagnosed in people at ages as young as 20.

In general, people with Birt–Hogg–Dubé syndrome are at roughly seven times the risk of kidney cancer compared to the unaffected population. Estimates of the incidence among people with the disease range from 14%–34%. Rarely, it is associated with clear cell renal cell carcinoma and papillary renal cell carcinoma. If it develops in someone with BHD, renal cell carcinoma occurs later in life and has a poor prognosis. Though the types of tumor typically associated with BHD are considered less aggressive, cases of advanced or metastatic kidney cancer have been observed in people with the syndrome. Both benign and cancerous tumors can reduce kidney function over time as they grow larger.

Hereditary cancer syndromes underlie 5 to 10% of all cancers. Scientific understanding of cancer susceptibility syndromes is actively expanding: additional syndromes are being found, the underlying biology is becoming clearer, and commercialization of diagnostic genetics methodology is improving clinical access. Given the prevalence of breast and colon cancer, the most widely recognized syndromes include hereditary breast-ovarian cancer syndrome (HBOC) and hereditary non-polyposis colon cancer (HNPCC, Lynch syndrome).

Some rare cancers are strongly associated with hereditary cancer predisposition syndromes. Genetic testing should be considered with adrenocortical carcinoma; carcinoid tumors; diffuse gastric cancer; fallopian tube/primary peritoneal cancer; leiomyosarcoma; medullary thyroid cancer; paraganglioma/pheochromocytoma; renal cell carcinoma of chromophobe, hybrid oncocytic, or oncocytoma histology; sebaceous carcinoma; and sex cord tumors with annular tubules. Primary care physicians can identify people who are at risk of heridatary cancer syndrome.

Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is an autosomal dominant genetic condition that has a high risk of colon cancer as well as other cancers including endometrial cancer (second most common), ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin. The increased risk for these cancers is due to inherited mutations that impair DNA mismatch repair. It is a type of cancer syndrome.

Under the name constitutional mismatch repair-deficiency, (CMMR-D), it has been mapped to MLH1, MSH2, MSH6 or PMS2. Although these are the same genes mutated in the condition known as Lynch syndrome or hereditary nonpolyposis colorectal cancer, the mutations are biallelic in CMMR-D.

The term "childhood cancer syndrome" has also been proposed.Café-au-lait macules have been observed.

Peutz–Jeghers syndrome (often abbreviated PJS) is an autosomal dominant genetic disorder characterized by the development of benign hamartomatous polyps in the gastrointestinal tract and hyperpigmented macules on the lips and oral mucosa (melanosis). This syndrome can be classed as one of various hereditary intestinal polyposis syndromes and one of various hamartomatous polyposis syndromes. It has an incidence of approximately 1 in 25,000 to 300,000 births.

Attenuated familial adenomatous polyposis is a form of familial adenomatous polyposis, a cancer syndrome. It is a pre-malignant disease that can develop into colorectal cancer. A patient will have fewer than a hundred polyps located typically in right side of the colon. Cancer might develop as early as the age of five, though typically presents later than classical FAP.

Gardner syndrome consists of adenomatous polyps of the gastrointestinal tract, desmoid tumours, osteomas, epidermoid cysts, lipomas, dental abnormalities and periampullary carcinomas. The incidence of the syndrome is 1:14,025 with an equal sex distribution. It is determined by the autosomal dominant familial polyposis coli gene (APC) on chromosome

5.

Gardner syndrome can be identified based on oral findings, including multiple impacted and supernumerary teeth, multiple jaw osteomas which give a "cotton-wool" appearance to the jaws, as well as multiple odontomas, congenital

hypertrophy of the retinal pigment epithelium (CHRPE), in addition to multiple adenomatous polyps of the colon. Gardner syndrome is also associated with familial adenomatous polyposis and may manifest as aggressive fibromatosis (desmoid tumors) of the retroperitoneum.

Desmoid tumors arise most frequently from the aponeurosis of the rectus abdominal muscle of multiparous women. The extra-abdominal form is rare and desmoids of the breast may arise in the mammary gland or may occur as an extension of a lesion arising from the muscles of the chest wall. The incidence of mammary desmoid tumours is less than 0.2% of primary breast neoplasms.

In Gardner’s syndrome the incidence ranges from 4% to 17%. Desmoid tumours associated with Gardner’s syndrome have been shown to have an alteration of the β-catenin pathway and over express β-catenin.

Most patients with fundic gland polyps (FGPs) do not have any symptoms, and the diagnosis is made on gastroscopy done for other reasons. Retrospective analysis of patients with sporadic FGPs shows that a high percentage do have symptoms, but that this is more likely to be related to the underlying disease responsible for the polyposis. These symptoms include:

- epigastric pain

- nausea

- vomiting

- weight loss

The polyps on endoscopy are usually tiny, numerous and sessile, and usually scattered throughout the fundus of the stomach, where parietal cells are more numerous. They have the same colour as the gastric mucosa, and never have a stalk.

When the polyps are biopsied, the pathology typically shows shortened gastric pits, and both superficial and deep cystic lesions in the fundic glands, lined by all three types of cells of acid-producing mucosa: mucous, parietal and chief cells. As sometimes parietal cell hyperplasia may develop deep dilations of gland, one should be really strict in the diagnosis of FGPs (i.e. the presence of deep and superficial dilations). Infrequently, the two lesions may coexist. Foci of dysplasia can sometimes be seen.

From early adolescence, patients with this condition gradually (and much of the time 'silently') develop hundreds to thousands of colorectal polyps (and sometimes polyps elsewhere)—small abnormalities at the surface of the intestinal tract, especially in the large intestine including the colon or rectum. These may bleed, leading to blood in the stool. If the blood is not visible, it is still possible for the patient to develop anemia due to gradually developing iron deficiency. If malignancy develops, this may present with weight loss, altered bowel habit, or even metastasis to the liver or elsewhere. FAP can also develop 'silently' in some individuals, giving few or no signs until it has developed into advanced colorectal cancer.

Because familial polyposis develops very gradually over years, and can also manifest in an 'attenuated' form even more gradually, polyps resulting from FAP can lead to cancer developing at any point from adolescence to old age.

Depending on the nature of the defect in the APC gene, and whether it is the full or attenuated form, familial polyposis may manifest as polyps in colon or in the duodenal tract, or in any combination of these. Therefore, an absence of polyps in, for example, the rectum, may not of itself be sufficient to confirm absence of polyps. It may be necessary to consider and visually examine other possible parts of the intestinal tract. Colonoscopy is preferred over sigmoidoscopy for this, as it provides better observation of the common right-side location of polyps.

The genetic determinant in familial polyposis may also predispose carriers to other malignancies, e.g., of the duodenum and stomach (particularly ampullary adenocarcinoma). Other signs that may point to FAP are pigmented lesions of the retina ("CHRPE—congenital hypertrophy of the retinal pigment epithelium"), jaw cysts, sebaceous cysts, and osteomata (benign bone tumors). The combination of polyposis, osteomas, fibromas and sebaceous cysts is termed "Gardner's syndrome" (with or without abnormal scarring).

Age of onset is variable. The term 'Juvenile' in the title of Juvenile polyposis syndrome refers to the histological type of the polyps rather than age of onset.

Affected individuals may present with rectal bleeding, abdominal pain, diarrhea or anemia. On colonoscopy or sigmoidoscopy polyps that vary in shape or size are present. The polyps can be sessile or pedunculated hamartomatous polyps.

Polyps are most frequent in the stomach and large intestine, are also found in the small intestine, and are least frequent in the esophagus. A biopsy will reveal them to be hamartomas; the possibility that they progress to cancer is generally considered to be low, although it has been reported multiple times in the past. Chronic diarrhea and protein-losing enteropathy are often observed. Possible collateral features include variable anomalies of ectodermal tissues, such as alopecia, atrophy of the nails, or skin pigmentation

Fundic gland polyposis is a medical syndrome where the fundus and the body of the stomach develop many polyps. The condition has been described both in patients with familial adenomatous polyposis (FAP) and attenuated variants (AFAP), and in patients in whom it occurs sporadically.