Attenuated FAP

Definition

Definition of Attenuated FAP
Attenuated FAP is an inherited colorectal cancer syndrome and accounts for 1 percent of all cases of colorectal cancer. The “F” stands for familial, meaning it runs in families; “A” stands for adenomatous, the type of polyps detected in the colon and small intestine that can turn into cancer; and “P” stands for polyposis, or the condition of having lots of colon polyps. The gene for FAP is on the long arm of chromosome 5 and is called the APC gene.

Symptoms

Symptoms of Attenuated FAP
From early adolescence and onwards, patients with this condition develop hundreds to thousands of polyps. These may bleed, leading to blood in the stool. If the blood is not visible, it is still possible for the patient to develop anemia due to gradually developing iron deficiency. If malignancy develops, this may present with weight loss, altered bowel habit, or even metastasis to the liver or elsewhere.

The genetic determinant in familial polyposis may also predispose carriers to other malignancies, e.g., of the duodenum and stomach. Other signs that may point to FAP are pigmented lesions of the retina ("CHRPE - congenital hypertrophy of the retinal pigment epithelium"), jaw cysts, sebaceous cysts, and osteomata (benign bone tumors). The combination of polyposis, osteomas, fibromas and sebaceous cysts is termed Gardner's syndrome (with or without abnormal scarring).

Causes

Causes of Attenuated FAP
Familial adenomatous polyposis can have different inheritance patterns and different genetic causes. When this condition results from mutations in the APC gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to cause the disorder. The incidence of malignancy in these cases approaches 100%. In most cases, an affected person has one parent with the condition.

Mutations in the MUTYH gene are inherited in an autosomal recessive pattern, which means two copies of the gene must be altered for a person to be affected by the disorder. Most often, the parents of a child with an autosomal recessive disorder are not affected but are carriers of one copy of the altered gene.

Prenatal testing is possible if a disease-causing mutation is identified in an affected family member; however, prenatal testing for typically adult-onset disorders is uncommon and requires careful genetic counseling.

Diagnosis

Diagnosis of Attenuated FAP
The diagnosis of AFAP is more complex than that of classic FAP because of the wide phenotypic variation of the disease. Given the right-sided distribution of colonic polyps in AFAP, total colonoscopy rather than sigmoidoscopy has been advocated for screening of patients at risk. Some advise chromoendoscopy to highlight the polyp burden. Similar to FAP diagnosis, AFAP diagnosis is based on the combination of clinical findings and genetic testing.

Treatment

Treatment of Attenuated FAP
The treatment of AFAP depends largely on the polyp burden and location. In a patient with few adenomas, colonoscopic polypectomy and medical management with a cyclooxygenase-2 inhibitor are sufficient if all polyps can be adequately removed. The adenoma-carcinoma sequence in these patients does not seem to be accelerated; thus, an interval of 1 to 2 years between colonoscopies should be accurate. If multiple polyps are found during colonoscopy, clusters are detected in a specific location, or total colonoscopy is technically difficult, surgical resection is the treatment of choice for these patients. When indicated, a subtotal colectomy with an ileorectal anastomosis can be performed because of the relative sparing of the rectum in AFAP. The remaining rectum does need lifelong surveillance.

Prognosis

Prognosis of Attenuated FAP
Consult with your doctor.

Prevention

Prevention of Attenuated FAP
Consult with your doctor.