Extra-intestinal manifestations of familial adenomatous polyposis

Abstract

Familial adenomatous polyposis (FAP) is an autosomal dominantly inherited disorder, which results from a germ line mutation in the APC (adenomatous polyposis coli) gene. FAP is characterized by the formation of hundreds to thousands of colorectal adenomatous polyps. Although the development of colorectal cancer stands out as the most prevalent complication, FAP is a multisystem disorder of growth. This means, it is comparable to other diseases such as the MEN syndromes, Von Hippel-Lindau disease and neurofibromatosis. However, the incidence of many of its clinical features is much lower. Therefore, a specialized multidisciplinary approach to optimize health care-common for other disorders-is not usually taken for FAP patients. Thus, clinicians that care for and counsel members of high-risk families should have familiarity with all the extra-intestinal manifestations of this syndrome. FAP-related complications, for which medical attention is essential, are not rare and their estimated lifetime risk presumably exceeds 30%. Affected individuals can develop thyroid and pancreatic cancer, hepatoblastomas, CNS tumors (especially medulloblastomas), and various benign tumors such as adrenal adenomas, osteomas, desmoid tumors and dental abnormalities. Due to improved longevity, as a result of better prevention of colorectal cancer, the risk of these clinical problems will further increase. We present a clinical overview of extra-intestinal manifestations, including management and treatment options for the FAP syndrome. Furthermore, we provide recommendations for surveillance of FAP complications based on available literature.

Fig. 1

Genotype–phenotype correlations of extra-intestinal familial adenomatous polyposis (FAP) manifestations according to the available literature.,,, The APC gene consists of 15 exons. The highest cumulative frequencies of extra-colonic manifestations are found between codons 976–1,067 and 1,310–2,011. The margins of codon regions associated with extra-intestinal manifestations are not absolute and merely provide a guideline. No genotype–phenotype correlations have been established for pancreatic carcinoma, brain tumors or adrenal gland adenomas. CHRPE congenital hypertrophy of the retinal pigment epithelium.