Genetic characteristics and extracolonic phenotypic manifestations in patients with familiar adenomatous polyposis.

Autores de IIS La Fe

• Víctor Argumánez Tello

  Autor

• Vicente María Lorenzo-Zúñiga García

  Autor

• Marco Bustamante Balén

  Autor

• Sonia Garcia Garcia

  Autor

• Isabel Terol Chafer

  Autor

• Juan Silvestre Oltra Soler

  Autor

• 

  Vicente Pons Beltrán

  Autor

Grupos

• Endoscopia Digestiva y Hepática

  

  Leader

  Vicente Pons Beltrán

• Investigación Traslacional en Genética

  

  Leader

  Francisco Martínez Castellano

Abstract

INTRODUCTION: Familial adenomatous polyposis (FAP) is a hereditary disease caused by mutations in the APC gene, which is also associated with extracolonic manifestations. The objective was to characterize the extracolonic manifestations in a cohort of patients with classic FAP and the possible genotype-phenotype association. MATERIALS AND METHODS: The study design was observational and descriptive. Demographic, clinical, and genetic variables were collected based on the type of mutation (frameshift, nonsense, splicing, rearrangement, and others). RESULTS: We included 45 patients with FAP (mean age 47years, range 21-78; 51% female), belonging to 21 families, with a median of 2 (range 0-6) manifestations per patient. Eighty percent (n=36) had upper digestive tract involvement, with duodenal adenomas (73%), fundic gland polyposis (56%), and ampullary adenoma (36%) being the most frequent findings. The most common extraintestinal manifestations were desmoid tumors (16%) and papillary thyroid carcinoma (13%). Thirty eight percent of the patients presented an aggressive phenotype (SpigelmanIII-IV, high-grade dysplasia, invasive neoplasia, desmoid tumor, and papillary thyroid carcinoma). The most common genetic mutations were frameshift (56%), nonsense (26%), and splicing (16%), primarily located in exon15 (50%). No significant correlation was found between the type of genetic mutation and the severity or location of phenotypic manifestations. CONCLUSIONS: One-third of patients with FAP present an aggressive phenotype, without a demonstrated correlation between the type of genetic alteration and the phenotypic manifestations.

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Keywords

• APC gene; Familial adenomatous polyposis; Gen APC; Genetic mutation; Poliposis adenomatosa familiar; Variante patogénica