FAP and Other Hereditary Causes of Intestinal Polyps
SUMMARY:
Familial Adenomatous Polyposis (FAP) is an autosomal dominant hereditary cancer syndrome. Individuals with this condition are prone to the development of polyps in the large bowel with the potential to become cancerous in childhood and in adulthood. The two forms of FAP, classic vs. attenuated, are caused by variants in the same gene but are distinguished based on the number of polyps in affected family members. In addition to FAP, there are other genetic causes of colorectal polyposis that should be considered in individuals with this presentation.
Clinical Features
Classic FAP
- Adenomatous colon polyps: > 100 throughout lifetime
- Cancer Risks
- Colon cancer: Lifetime risk approaches 100%
- Desmoid tumors: Intra-abdominal 10% to 24%
- Duodenal or gastric cancer: Up to 10%
- Thyroid cancer (cribriform-morular variant): 1% to 12%
- Hepatoblastoma: 0.4% to 2.5%
- Pancreatic cancer: 1% to 2%
- Medulloblastoma: 1%
- Multifocal or bilateral congenital hypertrophy of the retinal pigment epithelium (CHRPE)
- Dental findings: Supernumerary teeth or congenitally missing teeth
- Benign cutaneous lesions: Fibromas and epidermoid cysts
Attenuated FAP
- 10 to 100 adenomatous colon polyps throughout lifetime
- Cancer diagnoses generally occur at older ages than classic FAP
- Lifetime colon cancer risk 70%
- Extra-colonic manifestations are uncommon
Genetics
- Autosomal dominant; 30% of cases are de novo
- Caused by pathogenic variants in the APC gene
Diagnosis
- Clinical diagnosis applies to patients with >100 cumulative adenomatous polyps
- Targeted genetic testing is appropriate when a family member has been diagnosed with FAP or another hereditary polyposis
- Multi-gene panel testing is often recommended for individuals with multiple colorectal polyps and no distinguishing syndromic features
Management
- Referral to cancer genetics and oncology for counseling and management
- Follow-up generally includes
- Regular colonoscopies with polypectomies beginning in early adolescence
- Consideration of risk-reducing colectomy
- Regular screenings for other associated cancers (upper endoscopy, thyroid ultrasounds)
- Pediatricians should be aware of any family history of FAP and recommendations for early cancer screenings
Note: Because medical interventions can prevent severe morbidity and mortality, FAP is on the ACMG list of secondary findings. The ACMG document makes the following recommendations:
- In the course of genetic testing for research or clinical care, the laboratory may identify variants in genes unrelated to the initial indication for testing, but nevertheless may have important health implications
- Results of such secondary findings should be communicated to the individuals who may benefit from this knowledge
- An individual can ‘opt out’ of receiving secondary findings
Other Genetic Conditions Associated with Polyposis
- MUTYH-Associated Polyposis (MAP)
- Autosomal recessive; Biallelic pathogenic variants in the MUTYH gene
- <100 colorectal polyps
- Increased risk for colorectal cancer | Median age of onset >50 years
- Increased risk (5%) for duodenal cancer and duodenal adenomas
- Peutz-Jeghers Syndrome
- Autosomal dominant; pathogenic variants in the STK11 gene
- Two or more polyps in the GI tract with distinct hamartomatous histopathology
- Melanocytic macules on lips, nose, mouth, eyes, genitals, and fingers, which may fade with puberty
- Increased risk of breast, ovarian, and other cancers
- Juvenile Polyposis Syndrome
- Autosomal dominant; pathogenic variants in the BMPR1A or SMAD4 genes
- Multiple GI polyps with juvenile histology
- Epistaxis, bleeding, and telangiectasias (with SMAD4 variants)
- POLD– and POLE– Associated Polyposis
- Autosomal dominant
- 30 to 100 adenomatous polyps
- Lifetime risk of colon cancer >20%
- Limited evidence of other associated cancer risks
KEY POINTS:
- FAP is a familial cancer syndrome associated with multiple colorectal polyps with a high risk of colon and other cancers
- Consider referral to genetics for patients who present with any of the following
- Colorectal polyps: >10
- A family history of colon cancer or >10 colon polyps, especially if cancer was diagnosed at relatively young ages (<50)
- Extra-colonic manifestations such as CHRPE, hepatoblastoma, desmoid tumors, or cribriform-morular variant of papillary thyroid cancer
- Features of other polyposis syndromes such as hyperpigmented lesions or polyps with juvenile or hamartomatous histology
- Management includes aggressive systematic screening for colon polyps and other associated cancers
Learn More – Primary Sources:
ACMG and NSGC Joint Practice Guidelines: Referral Indications for Cancer Predisposition Assessment
GeneReviews – APC-Associated Polyposis Conditions
ACOG Committee Opinion 793: Hereditary cancer syndromes and risk assessment.
Locate a Genetic Counselor or Genetics Services:

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