On this page
Familial adenomatous polyposis
Without preventive treatment, these polyps almost invariably progress to colorectal cancer, typically before age 40. FAP accounts for approximately 1% of all colorectal cancer cases in the UK and affects around 1 in 10,000 to 15,000 individuals. Early diagnosis through genetic testing and regular surveillance can substantially reduce cancer risk.
Available at Jeen Health
Clinical tests that include this
Overview
Familial adenomatous polyposis represents one of the most well-characterised inherited cancer predisposition syndromes. The hallmark feature is the development of numerous adenomatous polyps throughout the large intestine, usually beginning during the teenage years or early twenties. These polyps are benign initially, but their sheer number creates an almost certain risk of malignant transformation if left untreated. Research suggests that individuals with classic FAP develop multiple adenomatous growths that can number from hundreds to several thousand, creating extensive polyp coverage visible during colonoscopy [PMID:19762983]. The condition follows an autosomal dominant inheritance pattern, meaning a single pathogenic variant in one copy of the responsible gene is sufficient to cause disease.
Beyond the gastrointestinal tract, FAP can affect multiple organ systems. Some individuals develop polyps in the upper digestive tract, particularly the duodenum and stomach, as well as various benign growths elsewhere in the body. Extra-colonic manifestations may include specific types of benign bone tumours called osteomas, dental abnormalities such as extra teeth or unerupted teeth, and characteristic pigmented lesions on the retina of the eye called congenital hypertrophy of the retinal pigment epithelium. When certain combinations of these extra-intestinal features occur alongside the polyps, the condition may be referred to as Gardner syndrome, though Gardner syndrome represents part of the FAP spectrum rather than a distinct entity.
The natural history of untreated FAP is well documented. Without preventive surgery, the vast majority of affected individuals will develop colorectal cancer, with malignant transformation occurring at substantially younger ages than seen in sporadic colorectal cancer. This predictable progression has made FAP an important condition within the NHS Genomic Medicine Service, with established care pathways for surveillance and risk-reducing interventions. Early identification through genetic testing enables affected individuals and their families to access appropriate monitoring and treatment before cancer develops, fundamentally altering the prognosis.
Symptoms & clinical features
The clinical presentation of FAP varies considerably depending on the age of the individual and the extent of polyp development. Most people with FAP remain asymptomatic during childhood and early adolescence, with polyps beginning to appear typically between ages 10 and 15, though they may develop earlier or later. The polyps themselves usually cause no symptoms initially, which is why surveillance colonoscopy is essential for early detection. As polyp numbers increase and individuals reach their twenties and thirties, symptoms may begin to emerge [PMID:19762983].
When symptoms do occur, they often relate to the physical presence of numerous polyps within the bowel. Rectal bleeding is among the most common presenting features, ranging from small amounts of bright red blood noticed on toilet paper to more substantial bleeding mixed with stool. Changes in bowel habits frequently develop, including diarrhoea, constipation, or alternating patterns. Some individuals experience abdominal cramping or discomfort, though severe pain is uncommon unless complications such as obstruction or cancer have developed. Anaemia may result from chronic low-level bleeding, potentially causing fatigue, pallor, and shortness of breath during physical activity. Unexplained weight loss can occur, particularly as polyp burden increases or if malignant transformation has begun.
Extra-colonic features may be noticed before gastrointestinal symptoms become apparent. Parents might observe unusual lumps on a child's skull or jaw, representing osteomas, or dental professionals may identify supernumerary teeth or other dental anomalies during routine examinations. The retinal lesions characteristic of FAP cause no visual symptoms and are only detectable during specialist ophthalmological examination. Some individuals develop desmoid tumours, which are locally aggressive fibrous growths that most commonly occur in the abdominal wall or within the abdomen itself. Whilst not cancerous, desmoid tumours can cause significant complications through compression of adjacent structures and represent one of the leading causes of death in FAP patients who have undergone preventive colectomy. Upper gastrointestinal polyps, particularly in the duodenum, may occasionally cause symptoms such as abdominal discomfort or bleeding, though they are often detected through surveillance endoscopy before becoming symptomatic.
Video: Is cancer in your genes?
Affected organs
The colon and rectum bear the primary disease burden in FAP, with adenomatous polyps carpeting the mucosal surface in untreated individuals. These polyps vary in size from tiny millimetre-scale lesions to growths several centimetres in diameter. The entire large bowel is typically affected, though polyp density may vary between different segments. Without surgical intervention, the accumulated genetic changes within these polyps lead inexorably towards invasive colorectal carcinoma.
The upper gastrointestinal tract represents the second most significant site of involvement. Duodenal adenomas develop in most FAP patients as they reach adulthood. These polyps cluster particularly around the ampulla of Vater, where the bile and pancreatic ducts enter the duodenum, creating a specific cancer risk in this location. Gastric polyps are also common, though these are usually fundic gland polyps with very low malignant potential, unlike the adenomatous polyps seen in the colon. The small bowel beyond the duodenum is rarely affected. Desmoid tumours, when they occur, most frequently arise in the mesentery of the small intestine or the abdominal wall, particularly following abdominal surgery. These lesions can cause substantial morbidity through local invasion and compression of bowel, blood vessels, or ureters. The thyroid gland shows increased cancer risk in FAP, particularly papillary thyroid carcinoma in women. Hepatoblastoma, a rare liver cancer of early childhood, occurs at markedly elevated frequency in children with FAP, prompting specific surveillance recommendations for young patients. Brain tumours, specifically medulloblastomas, show a slight increase in incidence, though the absolute risk remains low. Skeletal manifestations include osteomas, most commonly affecting the mandible and skull, whilst dental abnormalities encompass supernumerary teeth, odontomas, and unerupted permanent teeth.
Risks & severity
The severity of FAP is primarily determined by the exceptionally high risk of colorectal cancer development without preventive intervention. Evidence suggests that without prophylactic colectomy, malignant transformation of adenomatous polyps occurs in nearly all affected individuals, typically at younger ages than sporadic colorectal cancer [PMID:12877894]. This aggressive natural history explains why prophylactic colectomy remains the cornerstone of management for most affected individuals.
Extra-colonic cancer risks contribute significantly to long-term morbidity and mortality, particularly after prophylactic bowel surgery has addressed the primary colorectal threat. Duodenal cancer represents an important cause of cancer death in FAP patients who have undergone colectomy. Papillary thyroid carcinoma shows increased incidence, particularly in women. Hepatoblastoma affects a notable proportion of children with FAP, representing a substantially elevated risk compared to the general paediatric population. Pancreatic cancer, gastric cancer, and central nervous system tumours all show modest elevation in risk, though absolute numbers remain relatively small. Desmoid tumours develop in a significant minority of FAP patients, with higher risk following abdominal surgery. Whilst not malignant, these lesions cause substantial morbidity and represent a leading cause of death in post-colectomy FAP patients, as they can encase vital structures and prove resistant to treatment.
The severity spectrum in FAP shows considerable variation, influenced partly by the specific location and nature of the pathogenic variant involved. Classic FAP, characterised by hundreds to thousands of polyps, represents the most common presentation. Attenuated FAP describes a milder phenotype with fewer polyps, typically numbering between 10 and 100, developing later in life with colorectal cancer risk emerging at older ages than in classic FAP. Some individuals with attenuated disease may not develop their first polyps until their thirties or even forties, creating diagnostic challenges. Genotype-phenotype correlations exist, with variants affecting particular regions of the APC protein associated with different severity patterns, though considerable individual variation occurs even within families carrying identical variants.
Genetic causes
Pathogenic variants in APC account for the vast majority of FAP cases. This gene, located on chromosome 5, encodes a protein that plays a critical role in regulating cellular proliferation and maintaining genomic stability [PMID:23925302]. Working as a tumour suppressor, the APC protein helps prevent cells from growing and dividing too rapidly or in an uncontrolled manner. One of its key functions involves regulating beta-catenin levels within cells. The APC protein participates in a cellular complex that marks beta-catenin for destruction; when beta-catenin accumulates excessively, it migrates to the nucleus and activates genes that promote cell proliferation.
When a pathogenic variant disrupts APC function, this regulatory mechanism fails. Beta-catenin builds up inside cells and enters the nucleus, where it switches on proliferation-promoting genes. This loss of growth control creates a permissive environment for polyp formation. Each cell in an affected individual carries one functional and one non-functional copy of APC. Polyps develop when the remaining functional copy sustains a somatic mutation, leaving the cell with no working APC protein. This explains why, despite inheriting the condition from birth, polyps typically do not appear until adolescence - time is required for random second mutations to accumulate in sufficient numbers of colonic cells. Beyond beta-catenin regulation, the APC protein also participates in other cellular processes including cell adhesion, migration, chromosome segregation during cell division, and apoptosis, and disruption of these functions may contribute to tumour development.
The location of a pathogenic variant within APC influences disease severity through genotype-phenotype correlations. Variants affecting the central region of the gene, particularly in what is termed the mutation cluster region, typically produce classic FAP with profuse polyposis and early cancer risk. Variants near the beginning or end of the gene more commonly result in attenuated FAP with fewer polyps and later onset. Variants in a specific region around codon 1309 associate with particularly severe disease, sometimes with polyp development beginning in childhood.
However, these correlations show considerable overlap, and individuals with identical variants may show different phenotypic severity even within the same family, suggesting that modifier genes and environmental factors influence expression. A proportion of individuals meeting clinical criteria for FAP do not have an identifiable APC pathogenic variant despite comprehensive genetic testing, and research suggests some of these cases may involve variants in the MUTYH gene, though MUTYH-associated polyposis typically requires two pathogenic variants and shows a slightly different phenotype.
- APC APC regulator of Wnt signaling pathwayThe APC gene, or APC regulator of Wnt signalling pathway, is crucial for regulating cell growth and division, acting as a tumour suppressor primarily associated with familial adenomatous polyposis (FAP).
Inheritance pattern
Familial adenomatous polyposis follows an autosomal dominant pattern of inheritance. This means that inheriting a single pathogenic variant in one copy of APC from one parent is sufficient to cause the condition. Each child of an affected parent has a 50% (1 in 2) chance of inheriting the familial pathogenic variant and therefore developing FAP themselves. The condition affects males and females equally, and an affected individual can pass the variant to children of either sex.
Most individuals diagnosed with FAP have inherited the pathogenic variant from an affected parent, representing true familial cases. However, a significant minority of cases arise from de novo variants, occurring for the first time in the affected individual with no prior family history of the condition. These de novo variants typically arise spontaneously during the formation of the egg or sperm cell from which the individual developed, or very early in embryonic development. When a person has FAP due to a de novo variant, their siblings are not at increased risk, but the affected individual's own children will face the 50% inheritance risk. Genetic testing of both parents can help distinguish between inherited and de novo variants, which has important implications for counselling other family members about their risks.
Once a pathogenic APC variant has been identified in a family member with FAP, predictive genetic testing becomes available for at-risk relatives, including children. This testing can definitively determine whether a relative has inherited the familial variant before any symptoms or polyps develop, enabling early surveillance for those who test positive and providing reassurance and release from screening for those who test negative. In the UK, predictive testing for children is generally offered from around age 10-12 years, or earlier if there are clinical indications, as this allows implementation of colonoscopic surveillance at an appropriate age. Genetic counselling is an integral part of this process, helping families understand inheritance patterns, interpret test results, and make informed decisions about testing and management.
Each child has a 50% chance of inheriting the pathogenic variant, regardless of sex.
Diagnosis & testing
Diagnosis of familial adenomatous polyposis typically combines clinical findings with genetic testing confirmation. The initial suspicion often arises during colonoscopy performed either as part of family screening or following investigation of symptoms. The presence of 100 or more adenomatous polyps in the colon and rectum establishes a clinical diagnosis of classic FAP. For individuals with fewer polyps, particularly if these develop later in life, the diagnosis may be attenuated FAP, though distinguishing this from other polyposis syndromes requires careful evaluation. Some individuals present with characteristic extra-colonic features such as congenital hypertrophy of the retinal pigment epithelium, osteomas, or dental abnormalities before gastrointestinal features become apparent, raising clinical suspicion that prompts genetic testing.
Genetic testing through analysis of APC provides definitive diagnosis and is available through the NHS Genomic Medicine Service for individuals meeting clinical criteria or with a family history of FAP. Identification of a pathogenic variant confirms the diagnosis and enables predictive testing of at-risk family members. Some individuals meeting clinical diagnostic criteria for FAP do not have an identifiable APC pathogenic variant despite comprehensive sequencing and deletion/duplication analysis. Some of these cases may involve MUTYH testing, particularly if features suggest attenuated polyposis, though MUTYH-associated polyposis follows recessive rather than dominant inheritance. Referral for genetic testing in the UK typically occurs through clinical genetics services, often following identification of polyposis on colonoscopy or when there is a known family history. The relevant NHS Genomic Medicine Service testing criteria fall under the Inherited Colorectal Cancer and Polyposis R-codes (R207 covers FAP specifically), facilitating access to appropriate genetic testing and ensuring consistent standards across the country. Individuals diagnosed with FAP or their at-risk family members should have access to genetic counsellors who can explain test results, discuss implications for relatives, and coordinate appropriate surveillance and management.
Management & lifestyle
The management of familial adenomatous polyposis centres on preventing colorectal cancer development through a combination of surveillance and prophylactic surgery, alongside monitoring for extra-colonic manifestations. Once FAP is diagnosed or an individual is known to carry a pathogenic APC variant, regular colonoscopic surveillance typically begins from around age 12-14 years (earlier if symptoms develop), performed initially at yearly intervals. This surveillance allows clinicians to monitor polyp development and determine the optimal timing for preventive surgery. The decision about when to recommend colectomy balances cancer risk against the impact of major surgery, taking into account factors including polyp burden, presence of advanced adenomas, family history of early cancer, and the individual's preferences and circumstances.
Prophylactic colectomy remains the definitive risk-reducing intervention for colorectal cancer in FAP. The timing of this surgery typically occurs during late adolescence or early twenties, though individual circumstances vary. Two main surgical approaches exist: total colectomy with ileorectal anastomosis, which removes the colon but preserves the rectum, or proctocolectomy with ileal pouch-anal anastomosis, which removes both colon and rectum. The choice between these procedures depends on rectal polyp burden, genetic factors, patient preference, and surgical expertise. Individuals who retain their rectum require ongoing surveillance of the remaining rectal segment, as polyps will continue to develop there, albeit at lower density than in the colon. Those undergoing complete removal of colon and rectum have eliminated the colorectal cancer risk but face functional implications regarding bowel habit.
Upper gastrointestinal surveillance through oesophago-gastro-duodenoscopy begins from around age 25-30 years, performed at intervals of 1-5 years depending on polyp findings, using the Spigelman staging system to classify duodenal polyposis severity. Management of duodenal polyps may involve endoscopic removal of larger lesions, though complete clearance is usually impossible given polyp numbers. In cases of severe duodenal polyposis or duodenal cancer development, surgical options including pancreas-preserving duodenectomy may be considered, though this represents major surgery with significant morbidity. Women with FAP should be offered thyroid surveillance given increased papillary thyroid cancer risk, typically through annual neck palpation and consideration of thyroid ultrasound. Children diagnosed with FAP, particularly those under age five, may be offered hepatoblastoma surveillance through measurement of serum alpha-fetoprotein and liver ultrasound. There is no established screening for desmoid tumours, as these typically present symptomatically, though some centres perform periodic abdominal imaging.
Lifestyle considerations include maintaining regular contact with specialist services experienced in FAP management, as this is a lifelong condition requiring ongoing surveillance even after prophylactic surgery. Research suggests non-steroidal anti-inflammatory drugs may reduce polyp burden, though these are not a substitute for surgery and their role remains under investigation. Genetic counselling should be available to discuss family planning, predictive testing of children, and implications for other family members. The NHS manages FAP through specialist multi-disciplinary teams including colorectal surgeons, gastroenterologists, clinical geneticists, genetic counsellors, and specialist nurses, ensuring coordinated care across the patient's lifetime.
UK care pathway
Within the UK, familial adenomatous polyposis is managed through the NHS Genomic Medicine Service using established care pathways that ensure consistent access to genetic testing, surveillance, and treatment across the country. Individuals with suspected FAP, either through clinical findings or family history, are typically referred to clinical genetics services for assessment and genetic testing. The relevant testing pathway falls under the Inherited Colorectal Cancer and Polyposis category within the National Genomic Test Directory, with R207 specifically covering FAP and R210.2 covering early-onset or family history of colorectal cancer or polyposis. This framework ensures that appropriate individuals receive timely genetic testing and that results are interpreted by professionals with expertise in hereditary cancer syndromes.
Once a diagnosis is established, care is coordinated through specialist inherited colorectal cancer services, often involving multi-disciplinary team approaches combining gastroenterology, colorectal surgery, clinical genetics, and specialist nursing. Access to genetic counsellors is a key component of the pathway, providing support for newly diagnosed individuals, facilitating predictive testing for at-risk family members, and ensuring that relatives are appropriately informed and offered testing and surveillance. Surveillance protocols follow nationally agreed guidelines, with colonoscopy, upper gastrointestinal endoscopy, and other monitoring investigations performed at specialist centres experienced in managing polyposis syndromes. When prophylactic surgery is required, referral to surgeons with specific expertise in FAP ensures optimal outcomes and access to procedures such as ileal pouch surgery. Long-term follow-up remains within these specialist services, recognising that FAP requires lifelong monitoring for extra-colonic manifestations even after colorectal cancer risk has been addressed through surgery.
Frequently asked questions
If I have FAP, will I definitely get bowel cancer?
Without preventive treatment, the risk of developing colorectal cancer is extremely high. However, prophylactic surgery to remove the colon before cancer develops can prevent this outcome, which is why clinical teams typically recommend regular surveillance and discuss the timing of preventive surgery based on your individual circumstances.
Can my children be tested for FAP before polyps develop?
Yes, once a pathogenic APC variant has been identified in your family, predictive genetic testing is available for your children through the NHS. Testing is typically offered from around age 10-12 years, allowing time for discussion with a genetic counsellor and enabling early surveillance for those who test positive. Children who do not inherit the familial variant do not need colonoscopy surveillance.
What happens to bowel function after preventive surgery?
This depends on which operation you have. If you have a total colectomy with ileorectal anastomosis (keeping your rectum), bowel function is usually reasonably good, though you may have more frequent bowel movements than before. If you have a proctocolectomy with ileal pouch (removing both colon and rectum), surgical teams provide detailed counselling about bowel function expectations before surgery, and most people eventually achieve acceptable bowel control, though frequency may be higher than normal.
Do I still need surveillance after having my colon removed?
Yes, ongoing surveillance remains important. If your rectum was preserved, you will need regular examinations of the remaining rectal segment as polyps will continue to develop there. All FAP patients require upper gastrointestinal endoscopy to monitor the duodenum regardless of what bowel surgery was performed. Additional surveillance for thyroid and other potential sites may also be recommended depending on your individual circumstances.
My sibling has FAP but I haven't been tested - what should I do?
You should ask your GP to refer you to clinical genetics services for assessment and discussion of genetic testing. If you have inherited the familial APC variant, early surveillance can detect polyps before cancer develops. If you have not inherited the variant, you can be reassured that you are not at increased risk and do not need ongoing colonoscopy surveillance. A genetic counsellor can explain the implications of testing and help you make an informed decision.
References
- Waller A, Findeis S, Lee MJ. Familial Adenomatous Polyposis. Journal of pediatric genetics. 2016. PMID: 27617147
- Cruz-Correa M, Giardiello FM. Familial adenomatous polyposis. Gastrointestinal endoscopy. 2003. PMID: 14652558
- Armitage NC. Familial adenomatous polyposis. Journal of the Royal Society of Medicine. 1992. PMID: 1311383
- Eizuka M, Toya Y, Kosaka T. Attenuated Familial Adenomatous Polyposis. Internal medicine (Tokyo, Japan). 2023. PMID: 36725040
- Li M, Zhang X, You Y. Familial adenomatous polyposis and gastric cancer. QJM : monthly journal of the Association of Physicians. 2026. PMID: 41075183
- Burt RW. Screening and Survival in Familial Adenomatous Polyposis. Journal of clinical gastroenterology. 2016. PMID: 26535482
- Stanich PP, Sullivan B, Kim AC. Endoscopic Management and Surgical Considerations for Familial Adenomatous Polyposis. Gastrointestinal endoscopy clinics of North America. 2022. PMID: 34798980
- Bhurwal A, Prochilo G, Patel AV. Familial Adenomatous Polyposis. The American journal of the medical sciences. 2020. PMID: 32278488