I. Lynch syndrome
Lynch syndrome (Lynch syndrome) is an autosomal dominant disorder caused by germline mutations in the mismatch repair gene (MMR). The disease has the following characteristics.
(1) Early age of onset, with a median age of about 44 years, and the time required for its progression from adenoma to adenocarcinoma is relatively short, taking 8-10 years in normal subjects to progress from adenoma to adenocarcinoma, but only 2-3 years in patients with Lynch syndrome;
(2) Proximal colon is the most common, and about 70% of them are located in the proximal part of the splenic flexure;
(3) Multiple primary colorectal cancers are significantly more common;
(4) The incidence of extraintestinal malignant tumors is high, and simultaneous and heterochronic multiple primary cancers such as endometrial cancer, ovarian cancer, gastric cancer, intrahepatic bile duct cancer, urinary tract tumors and skin cancer are significantly higher than normal population.
(5) Hypofractionated adenocarcinoma and mucinous adenocarcinoma are common and accompanied by lymphocytic infiltration or aggregation of lymph-like cells;
(6) Vertical inheritance and family aggregation;
(7) Most of them show swelling growth rather than infiltrative growth. The prognosis is better.
Familial adenomatous polyposis
Familial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by APC mutations. The intestine is filled with polyps, ranging from tens to hundreds, or even thousands. Common symptoms include diarrhea, abdominal pain, and blood in the stool. Patients often suffer from anemia and weight loss due to prolonged consumption. The seriousness of this disease lies in the high cancer rate, which is often not limited to one location but is “multicentric”. Adenomatous polyps can appear at the age of 12 or 13 years old, and by the age of 20 years old, the polyps have spread all over the large intestine, and if left untreated, almost all cases will become cancerous by the age of 40 years old.
MUTYH-associated polyposis
MUTYH-associated polyposis (MAP) is an autosomal recessive disorder due to mutations in the MUTYH gene, and is very similar to familial adenomatous polyposis in its presentation. However, no APC mutation is found in genetic testing and there is no tumor microsatellite instability. However, once this guy shows his “fangs”, the victims will face more threats – patients with MUTYH mutation have a significantly higher risk of colorectal cancer.
Gardner syndrome (GS)
It is a rare autosomal dominant disorder with three major features: colorectal polyposis combined with multiple osteomas and soft tissue tumors.
V. Gliomatous polyposis syndrome (Turcot syndrome)
It is a rare clinical subtype of FAP, characterized by familial multiple colonic adenomas with central nervous system malignancies.
Sixth, melanotic polyposis (PJS)
PJS is associated with mutations in the SKT11 gene. The three main clinical features are skin mucosal discoloration, gastrointestinal misshapen polyps and familial inheritance. Typical cutaneous mucosal dark spots and/or intussusception, intestinal obstruction or bleeding may occur during childhood. The risk of polyp malignancy increases with age. Polyps can appear throughout the intestine.
VII. Familial Juvenile Polyposis of the Colon (FJIPC)
Autosomal dominant, mainly associated with mutations in SMAD4 or BMPR1A genes. FJIPC also has the “virtue” of “helping cancer”, which can significantly increase the risk of colorectal, small bowel, gastric and pancreatic cancer. Some patients with familial juvenile colonic polyposis may have congenital disorders such as pestle and mortar finger (toe), hypertrophic pulmonary osteoarthropathy, hydrocephalus, cleft lip, cleft palate, congenital heart disease, etc. Carriers of SMAD4 mutation sometimes develop hereditary associated capillary hemorrhage, which manifests as recurrent rhinorrhea, skin mucosa or pulmonary capillary dilation, and arteriovenous malformation of brain or liver.
VIII. PTEN malformation syndrome (PHTS)
PTEN mutations cause autosomal dominant genetic disorders, including Cowden syndrome and BRRS syndrome, which manifest as colorectal polyposis with multiple malformations, facial papules, acromegaly and oral mucosal papillomas. BRRS syndrome is also an autosomal dominant disorder caused by PTEN mutations and is characterized by colorectal polyposis, macrosomia, lipomatosis, hemangiomatosis and genital discoloration.