Familial adenomatous polyposis (FAP) also known as familial polyposis (affecting the colon), and Gardner Syndrome (colon and extracolonic manifestations), is a hereditary colorectal cancer syndrome associated with the development of hundreds to thousands of adenomatous polyps in the colorectum. It affects the entire life span from pediatrics to geriatrics with diagnosis and need for surgery usually in the teen-age years. There are no medical treatments for these patients and colectomy is necessary to prevent the inevitable occurrence of colorectal cancer. It is a lifetime concern for patients and families due to the development of extracolonic manifestations (either benign or malignant), the risk of rectal cancer (depending on the type of surgery performed) and a 50-percent chance of passing this condition to their children. Since the discovery of the adenomatous polyposis coli gene (APC) genetic testing is available for FAP. Testing provides early diagnosis and treatment, helping patients live normal lives by preventing unnecessary screening procedures and mitigating the risk of developing colorectal cancer.
Clinical Features: The cause of FAP is a germline mutation of the APC gene located on chromosome 5q21.1-3 The incidence of FAP is 1/8,300 to 1/14,025 live births,4 affects both sexes equally, is seen worldwide and is 1 percent of all colon cancers. Approximately one-third of FAP cases are spontaneous mutations. There is no family history of FAP. The average age of onset for polyp development is 15 years old (occuring in 50 percent of all FAP patients) and 95 percent of patients develop polyps by the age of 35.5,6 In an unscreened patient, symptoms usually appear by the age of 30, average age of diagnosis is 36, colorectal cancer diagnosis on average by 39, and death from colorectal cancer by a mean age of 42. Colorectal adenomas spread throughout the colon. The histopathology of adenoma development can be microadenomas in flat tissue, tubular, tubulovillous, villous adenomas and adenocarcinoma. Colorectal cancer is inevitable, primarily in the left colon, if a colectomy is not performed.7
FAP patients can have only polyposis or it can be associated with various extracolonic manifestations. Gardner Syndrome (old terminology) is FAP with extracolonic manifestations and Crails Syndrome is FAP with a brain tumor, specifically meduloblastomas.8
Patients with FAP can develop any number of extracolonic manifestations and these lesions can be benign or malignant. Benign extracolonic manifestations include:
- Ocular lesions of the retina, congenital hypertrophy of the retinal pigment epithelium (CHRPE)9-11
- Nasopharangeal angiofibromas (a rare highly vascular localized invasive tumor that occurs exclusively in the nares or nasopharynx of male adolescents)12
- Osteomas of the long bones13,14
- Radio-opaque jaw lesions of the mandible or maxilla15
- Dental abnormalities such as supernumerary teeth16
- Cutaneous lesions that usually develop in the teenage years such as sebaceous and epidermoid cysts located on the extremities, scalp, or face, soft tissue tumors such as lipomas, and fibromas13,17-18
- Desmoid tumors (benign fibromatous lesions that arise usually in the abdominal wall or mesentery)19
- Gastric (50 percent of patients), duodenal, jejunal, and ileum adenomas, and fundal gland retention polyps of the stomach (23 percent to 56 percent of patients).20-22
Malignant extracolonic manifestations associated with FAP are: cancers of the brain;8 thyroid, biliary tree and pancreas;23 duodenum and periampullary area;24 and hepatoblastoma.25 In FAP patients, brain tumors are specifically medulloblastomas presenting by the second decade of life; and thyroid cancer usually occurs by the third decade of life. Duodenal and periampullary cancers are the second leading cause of death in FAP patients after colorectal cancers. Hepatoblastomas are rare embryonic tumors of the liver that occur in the first five years of life in approximately 1.6 percent of the offspring of FAP parents.25 The relative risk for FAP patients to develop cancer is: brain (sevenfold), thyroid (eightfold), pancreas (fivefold), duodenal (331-fold), periampullary (124-fold), and hepatoblastoma (847-fold) greater than the general population.26
The germline mutation is a tumor suppressor or gatekeeper gene important in cell adhesion, signal transduction and transcription activation.27 There are more than 300 mutations, but the most common mutation is a deletion in codon 1309.28
Attenuated Familial Adenomatous Polyposis (AFAP)
AFAP is a less severe phenotype of FAP in which affected individuals develop fewer polyps -- less than 100 colorectal adenomas -- at a later age than those with typical FAP. Family members need to be screened with a colonoscopy rather than a sigmoidoscopy since the polyps are not evenly distributed through the colon in AFAP. Screening should begin in the teen-age years since these patients still have a 100-percent lifetime risk of colon cancer.29,30
Genetic testing is considered the standard of care in managing FAP.31,32 Indications for APC gene testing are: patients with 100 or more colorectal adenomatous polyps, first-degree relatives (10 years or older) of affected individuals with FAP; patients with greater than 20 cumulative colorectal adenomas,33 and first-degree relatives (10 years or older) of patients with attenuated FAP. There is one specific gene mutation found in a family and each at-risk person has a 50-50 chance of inheriting that gene mutation. To begin testing at risk persons, a family member with adenomas must be evaluated for a mutation.31,34 If a mutation is found, testing at-risk family members will provide a true positive or true negative result. If a mutation is not found, at-risk family members cannot be tested due to inconclusive results. It is important that the gene test is interpreted accurately so appropriate screening procedures can be recommended.
Commercially available genetic tests for FAP include: sequencing, linkage, protein truncation and a combination of protein truncation with conformation strand gel electrophoresis (CSGE), single-strand conformation polymorphism (SSCP) or sequencing.35-39 Since protein truncation detects disease-causing mutations, is less costly and has a shorter turnaround time, it is the preferred method of genetic testing.
It is imperative that genetic counseling accompany genetic testing. Counseling can occur when the diagnosis of FAP is made, the patient is considering reproductive options, a FAP patient is having their offspring screened or an at-risk patient considers genetic testing. Counseling should be done both pre- and post-testing. It helps the patient and family to understand medical and genetic information about FAP and provides emotional and psychological support for the entire family.
During the first precounseling visit, it is important to educate families about the clinical and management aspects of FAP, its hereditary nature, exploring family history and experiences and exploring perception of risk for FAP and cancer. In addition, the consequences of receiving gene positive or negative results and recommendations concerning screening guidelines for each possible test outcome should be given. It is critical that written informed consent for gene testing be obtained.40 Disclosure of the test result happens in the second post counseling visit. Patients with positive and negative gene test results have many concerns that can be addressed during this time including: anger, denial, social stigma, fear of surgery or death, interference with school or work, loss of insurability for gene positive patients, survivor guilt in gene negative mutation individuals or fears of what will happen to their affected family members.40-41 A follow-up session is important since patients with positive results may referrals for additional professional support warranted.
Screening: The best method for screening patients at risk for FAP is APC gene testing.42 If the patient is APC gene negative, then flexible sigmoidoscopy should be performed at least once at age 25 to confirm the negative genetic result. If the patient is APC gene positive (positive for a disease causing mutation), flexible sigmoidoscopy should be performed yearly until polyps are found, then surgery is recommended. If a mutation has not been found in a family or genetic testing cannot be done, at-risk individuals need frequent endoscopic screening. Screening begins between 10 and 12 years old with a yearly flexible sigmoidoscopy. The frequency of sigmoidoscopy is then decreased with each decade until age 50. When polyps develop surgery is recommended. After age 50, patients are advised to follow screening guidelines for the average person.42
Treatment and Nursing Care
The treatment goal for FAP is to prevent colorectal cancer. Colectomy is the only effective therapy that eliminates the development of colorectal cancer in FAP patients. The timing of surgery should depend on the number, size and histopathology of the polyps in the colon. In general, surgery is advised when polyps develop. Surgical options are: total proctocolectomy with a Brooke ileostomy or Kock pouch (continent ileostomy); subtotal colectomy with ileorectal anastomosis; and proctocolectomy with mucosal proctectomy and ileoanal pull-through with J pouch formation.43-45
Postoperative follow-up depends on the type of surgery a patient chooses. Patients with ileorectal anastomosis surgery require flexible sigmoidoscopies at least every six months due to the risk of rectal cancer.46-47 Patients with ileoanal pull-through surgery require endoscopic screening with biopsy if they develop adenomas in the pouch.48 Upper endoscopic surveillance is recommended for all patients due to the risk of developing upper tract polyps and cancer.24 Depending on the number of polyps, and histopathology, endoscopic surveillence can occur every six months to four years.
Presently, there is no medical treatment or primary chemopreventive agents to prevent polyp development in FAP. The prevention and regression of polyps in the retained rectum of ileorectal anastomosis surgical patients is effective, if treated in the short term, with sulindac and celecoxib.49-51 Celecoxib is the only drug approved by the Food and Drug Administration (FDA) for use in FAP patients as an adjunct therapy for ileorectal anastomosis patient for regression of their rectal polyps.52
Nursing care of the FAP patient involves support of all family members, patient education and pre-op and post-op care, and needs to be provided throughout the patient's life span. Emotional and psychological support is the biggest aspect of nursing care in FAP patients and their families.
The diagnosis and surgical treatment of FAP usually occurs in the teen-age years with support and education beginning earlier. Children in families with FAP usually have greater knowledge and more appropriate expectations than patients with a spontaneous mutation. Parents, grandparents, other family members and caregivers need to honestly address children's questions and concerns. Complications relating to the extracolonic manifestations requiring surgery or other management can occur at any age. Since this is a family disorder, encourage parents to talk openly about the disease with the affected and unaffected offspring. Obtaining an accurate family history helps with appropriate referrals to physicians, genetic counselors, colon cancer registries, support groups, surgeons, ostomy nurses and other families with FAP.
Affected individuals need to understand the hereditary nature of the disease including the 50-percent chance of passing this condition to their offspring. The disorder can still be inherited even if the parent's colon is removed, and individuals not affected with APC gene mutation negative cannot pass the disorder to their children. The consequences of gene positive, gene negative and no mutation test results with appropriate screening guidelines needs to be stressed to these patients regardless of age. Patients and their families need to be educated about about follow-up care. Depending on the type of colon surgery, the risk of colorectal cancer can be eliminated.
Patients must understand that ileorectal anastomosis surgery does not eliminate rectal cancer risk due to the retained rectum segment, and that screening by flexible sigmoidoscopy is necessary at least every six months. The importance of upper tract screening must be emphasized.
Preoperative care is just as important as postoperative care. Since surgery usually occurs in the teen-age years, it is important to address their concerns. Refer them to patients their own age who have experience with the type of surgery to be performed. Talking directly to patients helps them to understand what is expected and what will happen, especially if they need an ileostomy. If an ileostomy is needed, refer the family to an enterostomal (ET) nurse prior to surgery to obtain information on how to care for the ostomy post-op. They will have a better idea of how long they may be out of school, so the surgery can be planned accordingly. Parents of affected children should interact with experienced parents to obtain information, ideas and hints, and form a network of support.
FAP encompasses a lifetime of concern affecting many generations in a family because their lives are affected in a variety of ways. Hopefully advances in medical and surgical management will provide more options for the treatment of FAP patients.
Linda M. Hylind BS, RN, is a GI clinical and research nurse at The Johns Hopkins Hospital and University in Baltimore, Md.
Francis M. Giardiello is a professor of medicine and division director for gastroenterology and hepatology at the same facility.
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DID YOU KNOW
There is controversy within the medical community about whether it is ethical to screen children about genetic diseases. The following organizations and researchers have written articles concerning FAP and genetic testing: