Familial adenomatous polyposis (FAP)
Which are the symptoms?
The main feature is the development of hundreds of colorectal polyps. Equally characteristic is polyposis of the duodenum and sometimes the stomach, also with malignant potential. Thyroid, desmoid, pancreatic, and hepatic tumors (typically hepatoblastomas) may also occur. At the ocular level, it is characterized by congenital hypertrophy of the retinal pigment epithelium. Some infrequent variants of FAP are characterized by brain tumors (medulloblastoma), typical of Turcot syndrome, or osteomas of the skull and jaw, dental anomalies and epidermoid cysts (Gardner syndrome).
How is it diagnosed?
FAP and its variants are rare diseases. The cause of FAP, attenuated FAP and other variants (Gardner and Turcot syndrome) is a pathogenic variant (mutation) in the APC gene. Pathogenic variants in the APC gene are identified by gene sequencing. Sequencing is a molecular biology technique that identifies pathogenic variants using two techniques (Next Generation Sequencing and Multiplex ligation-dependent probe amplification). Based on personal and family history, suspicion of FAP is raised and genetic testing is indicated. Although patients often have a family history of FAP, up to 30% of FAP and AFAP cases are due to novel germline mutations ("de novo", i.e., not inherited from parents) in the APC gene. The APC gene, when mutated, causes rapid and uncontrolled multiplication of cells. This leads to the formation of numerous intestinal polyps, each with malignant potential.
How is it treated?
Different pathogenic variants of the APC gene can cause very different clinical pictures.
For this reason, patients with FAP require a highly specialized diagnostic and therapeutic pathway.
The goal is to diagnose and treat tumor precursors early. Depending on the body district at risk for cancer, a different surveillance strategy will be initiated. Prevention consists of regular surveillance of body districts at risk, in particular:
Colon-rectum: endoscopic surveillance by colonoscopy to prevent colorectal cancer by removing polyps (endoscopic polypectomy). When polyps become difficult to manage endoscopically because of number, size, and macroscopic appearance, prophylactic colectomy surgery is recommended. There are two types of prophylactic surgery: colectomy with anastomosis of the ileum to the rectum and proctocolectomy with anastomosis of the ileal pouch to the anus.
- Stomach and duodenum: surveillance by esophagogastroduodenoscopy to also evaluate the duodenal papilla. At the duodenal level, adenomas have an incidence of more than 90% and a median age of presentation of 52 years.
- Thyroid: thyroid ultrasound for early diagnosis of papillary tumor
- Desmoids: computed axial tomography or magnetic resonance imaging
- Pancreas: surveillance may be recommended in some cases
- Hepatoblastoma: serum alpha-fetoprotein and abdominal ultrasonography
- Brain: magnetic resonance imaging
- Eyes: slit lamp and indirect ophthalmoscopy