Familial Adenomatous Polyposis (FAP) Syndrome

Gardner Syndrome

Epidemiology and Etiology:

· APC mutations (5q21) (90%)

· Deletions in 8-12%

· subtypes:

· Classic (500-2500 colonic adenomas)

· Minimum 100 polyps in colon

· Cancer risk 100%

· Attenuated (average 30 polyps)

· Most in proximal colon

· Cancer risk 50%

· Gardner

· Classic FAP + lesions at other sites (listed below)

· Turcot

· Colonic polyposis + CNS tumours

· 2/3 have APC mutations

· 1/3 have HNPCC

·

Common sites:

· Colon

· Polyposis (> 100)

· Adenocarcinoma

· 39 y mean age in untreated individuals

· ganglioneuroma

· Small bowel

· Ampulla of Vater

· Adenoma

· Adenocarcinoma

· Stomach

· Adenoma

· Fundic gland polyp

· Adenocarcinoma

· Bone (mandible, skull, long bones)

· Osteoma

· Skin

· Epidermal cyst

· Pilomatricoma

· Soft Tissue

· Fibromatosis

· Thyroid

· Carcinoma

· CNS

· Medulloblastoma

· Liver

· Hepatoblastoma

· Congenital hypertrophy of the retinal pigment epithelium (CHRPE)

Gross features:

·

Histologic features:

· GI polyps:

· Vast majority are tubular adenomas

Immunophenotype:

Marker:

Sensitivity:

Specificity:

Molecular features:

· APC full gene sequencing is available

· Most accurate test – sensitivity <=90%

· MLPA or qPCR or SB for deletions

Other features:

· Colectomy advised when more than 20-30 adenomas with “advanced histology” have occurred

· Polypectomy recommended for adenomas with

· > 1cm

· Villous

· Severe dysplasia

· Symptomatic

· NSAIDs, particularly sulindac, may cause decrease in number of polyps

References:

· Kumar V, Fausto N, Abbas A. Robbins & Cotran Pathologic Basis of Disease, Seventh Edition. 7th ed. Saunders; 2004.

· Genetests.org