APC-Related Familial Adenomatous Polyposis: Clinical Diversity and Molecular Findings from a Single Center
2.INTERNATIONAL HEREDITARY CANCERS CONGRESS, Antalya, Turkey, 5 - 08 February 2026, pp.154-156, (Full Text)
- Publication Type: Conference Paper / Full Text
- City: Antalya
- Country: Turkey
- Page Numbers: pp.154-156
- Open Archive Collection: AVESIS Open Access Collection
- Eskisehir Osmangazi University Affiliated: Yes
Abstract
Objective: Conditions associated with APC pathogenic variants include familial adenomatous polyposis (FAP), which may present as the classic or attenuated form, and gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). FAP [MIM #175100] is an autosomal dominant colorectal cancer predisposition syndrome characterized by the development of numerous colorectal adenomatous polyps. The worldwide incidence of FAP is estimated to be 3–10 per 100,000 individuals, accounting for approximately 1% of all colorectal cancers. In addition to colorectal adenomas, extra-colonic manifestations such as desmoid tumors, congenital hypertrophy of the retinal pigment epithelium, osteomas, dental anomalies, epidermoid cysts, lipomas, and upper gastrointestinal tract polyps may also be observed in affected individuals. Materials-Methods: This study aimed to evaluate the clinical and molecular characteristics of 11 patients diagnosed with Familial Adenomatous Polyposis syndrome between 2021 and 2025 at the Eskisehir Osmangazi University Department of Medical Genetics. Results: Hereditary mutations in the APC gene were identified in 11 patients, and all of these variants were classified as pathogenic or likely pathogenic according to ACMG criteria. The most frequent alterations were frameshift variants in 54.5% (6/11), five due to small deletions and one to a duplication, all of which resulted in premature stop-codon formation. Of these six frameshift variants, three (50%) represented novel changes that have not been previously reported in the literature. Nonsense mutations accounted for 36.4% (4/11) of the cases, whereas a single splice-site variant was detected in one patient. The majority of the variants were located in exon 16, a functionally critical region of the APC gene that is frequently associated with the classical FAP phenotype. The ages of the patients ranged from 12 to 55 years (median: 27 years). Notably, two patients exhibited predominantly extra-colonic onset: one patient carrying a nonsense variant in exon 16 developed a mandibular desmoid tumor at the age of 12 years prior to the onset of colorectal polyposis,and another patient harboring a nonsense variant in exon 5 developed an ethmoid bone osteoma prior to being diagnosed with FAP at the age of 55 years. In addition, a patient with a frameshift mutation in exon 16 developed an abdominal-wall desmoid tumor after the onset of colorectal polyposis, representing a clinically significant but recognized extracolonic complication of FAP. Apart from these cases, all remaining patients initially presented with multiple colorectal polyps, consistent with the classical FAP presentation. In accordance with current clinical management recommendations, genetic counseling was provided to all patients, and targeted variant testing were recommended for at-risk family members. Conclusion: In this APC-related FAP cohort, all detected variants were pathogenic or likely pathogenic, with a predominance of truncating mutations and clustering in exon 16. The two patients with extracolonic onset prior to colorectal polyposis illustrate the phenotypic variability of APC-associated disease and highlight the need for early genetic testing and surveillance, particularly in individuals presenting with desmoid tumors or osteomas.