IllnessPolyposis coli, differential diagnosis

NGS +

[Sanger]

Familial adenomatous polyposis (FAP; Gardner syndrome) is a cancer predisposition syndrome characterized by hundreds to thousands of adenomatous colorectal polyps, with near universal progression to colorectal carcinoma by age 35-40 years. FAP causes less than 1% of all cases of colorectal carcinoma in Western countries. The majority of FAP cases are caused by germline mutations in the APC gene and are inherited in an autosomal dominant manner, although de novo germline mutations occur in up to one-third of cases. A milder, autosomal recessive form of FAP typically develops fewer than 100 polyps; it is caused by mutations in the MUTYH gene. In the differential diagnosis, consider Lynch syndrome (hereditary non-polyposis colon cancer, HNPCC), MSH3-associated polyposis, Peutz-Jeghers syndrome, PTEN hamartoma tumor syndrome, juvenile polyposis syndrome, hereditary mixed polyposis syndrome, NTHL1-associated polyposis and finally neurofibromatosis type 1. The detection probability of a pathogenic APC variant is highly dependent on the severity of colonic polyposis and family history. Detection rates are higher in classic polyposis than in attenuated phenotypes and higher in individuals with a positive family history. Pathogenic APC variants are detected in <30% of patients with attenuated phenotypes. Therefore, the clinical diagnosis cannot be excluded with certainty by a negative molecular genetic result.

Reference: https://www.ncbi.nlm.nih.gov/books/NBK1345/

• Allelic: Adrenocortical carcinoma, pediatric (TP53)
• Allelic: Basal cell carcinoma 7 (TP53)
• Allelic: Bone marrow failure syndrome 5 (TP53)
• Allelic: Choroid plexus papilloma (TP53)
• Allelic: Diamond Blackfan anaemia (RPS20)
• Allelic: Endometrial cancer, susceptibility to (MLH3)
• Allelic: Glioma susceptibility 1(TP53)
• Allelic: Li-Fraumeni syndrome (TP53)
• Allelic: Osteosarcoma (TP53)
• Allelic: Uveal melanoma, susceptibility to, 1 (MBD4)
• Adenomas, multiple colorectal (MUTHY)
• Brain tumor-polyposis syndrome 2 (APC)
• Colorectal cancer (TP53)
• Colorectal cancer, hereditary nonpolyposis, type 7 (MLH3)
• Colorectal cancer, somatic (FLCN)
• Colorectal cancer, susceptibility to, 10 (POLD1)
• Colorectal cancer, susceptibility to, 12 (POLE)
• Cowden syndrome 1 (PTEN)
• Cowden syndrome 6 (AKT1)
• Desmoid disease, hereditary (APC)
• Familial adenomatous polyposis 1 [FAP1] (APC)
• Familial adenomatous polyposis 3 (NTHL1)
• Familial adenomatous polyposis 4 (MSH3)
• Gardner Syndrom (APC)
• Hereditary mixed polyposis syndrome [Ashkenasi duplication] (GREM1)
• Juvenile polyposis/hereditary hemorrhagic telangiectasia syndrome (SMAD4)
• Multiple endocrine neoplasia IIA + IIB (RET)
• Peutz-Jeghers syndrome (STK11)
• Polyposis, juvenile intestinal (BMPR1A, SMAD4)
• RPS20-assoc hereditary nonpolyposis CRC (RPS20)
• Tumor predisposition syndrome 2 (MBD4)