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<p>Familial adenomatous polyposis (FAP) is an autosomal dominant genetic disorder primarily caused by pathogenic mutations in the adenomatous polyposis coli (<i>APC</i>) gene. Some FAP cases are clinically diagnosed even in the absence of a family history. Both the NCCN Clinical Practice Guidelines (Version 3.2024) and the Japanese Society for Cancer of the Colon and Rectum Guidelines for the Clinical Practice of Hereditary Colorectal Cancer Guidelines (2020) recommend genetic testing for FAP cases without a family history; however, its implementation is limited due to ethical and economic considerations. Herein, we report two cases in which genetic testing was performed on patients clinically diagnosed with FAP despite the absence of a family history. Case 1: A 44-year-old woman presented with transverse colon cancer and polyposis, identified using colonoscopy. Despite having no family history of FAP, she was diagnosed with attenuated FAP (AFAP) based on the preoperative findings. The patient underwent laparoscopic total colectomy and ileorectal anastomosis, followed by adjuvant chemotherapy and surgical treatment for the pulmonary metastasis. Genetic panel testing revealed no <i>APC</i> mutation but identified a <i>SMAD9</i> mutation classified as a variant of uncertain significance. Over a follow-up period exceeding 9&#xa0;years, the patient showed no recurrence of colorectal cancer or extracolonic manifestations of FAP. Case 2: A 44-year-old woman who had undergone colonoscopy since being diagnosed with polyps at the age of 29&#xa0;years presented with sigmoid colon cancer and polyposis. Despite having no family history of FAP, she was diagnosed with AFAP based on the preoperative findings. The patient underwent laparoscopic total colectomy with ileostomy, followed by ileostomy closure 6&#xa0;months later. Genetic testing performed the same year revealed an <i>APC</i> mutation. A CT scan at 1&#xa0;year and 7&#xa0;months postoperatively revealed a soft tissue mass suspected to be a desmoid tumor, and the patient is currently being followed up in the outpatient clinic. These cases emphasize the importance of genetic testing in the clinical management of FAP to ensure an accurate diagnosis and differentiation from related syndromes. Although <i>APC</i> mutations are detected in only 20–40% of patients undergoing genetic testing for FAP, <i>APC</i> mutation-negative cases are reported to have a milder phenotype. However, its genetic characteristics remain unclear. The role of <i>SMAD9</i> mutations is not yet fully understood, but identifying such mutations may deepen our understanding of genetic associations in colorectal polyposis syndromes.</p>

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Two cases of genetic testing for familial adenomatous polyposis without a family history

  • 期刊论文

  • 发表日期：

    2025年6月30日

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  • Yusuke Makutani,
  • Masayoshi Iwamoto,
  • Koji Daito,
  • Tadao Tokoro,
  • Kazuki Ueda,
  • Junichiro Kawamura

摘要

Familial adenomatous polyposis (FAP) is an autosomal dominant genetic disorder primarily caused by pathogenic mutations in the adenomatous polyposis coli (APC) gene. Some FAP cases are clinically diagnosed even in the absence of a family history. Both the NCCN Clinical Practice Guidelines (Version 3.2024) and the Japanese Society for Cancer of the Colon and Rectum Guidelines for the Clinical Practice of Hereditary Colorectal Cancer Guidelines (2020) recommend genetic testing for FAP cases without a family history; however, its implementation is limited due to ethical and economic considerations. Herein, we report two cases in which genetic testing was performed on patients clinically diagnosed with FAP despite the absence of a family history. Case 1: A 44-year-old woman presented with transverse colon cancer and polyposis, identified using colonoscopy. Despite having no family history of FAP, she was diagnosed with attenuated FAP (AFAP) based on the preoperative findings. The patient underwent laparoscopic total colectomy and ileorectal anastomosis, followed by adjuvant chemotherapy and surgical treatment for the pulmonary metastasis. Genetic panel testing revealed no APC mutation but identified a SMAD9 mutation classified as a variant of uncertain significance. Over a follow-up period exceeding 9 years, the patient showed no recurrence of colorectal cancer or extracolonic manifestations of FAP. Case 2: A 44-year-old woman who had undergone colonoscopy since being diagnosed with polyps at the age of 29 years presented with sigmoid colon cancer and polyposis. Despite having no family history of FAP, she was diagnosed with AFAP based on the preoperative findings. The patient underwent laparoscopic total colectomy with ileostomy, followed by ileostomy closure 6 months later. Genetic testing performed the same year revealed an APC mutation. A CT scan at 1 year and 7 months postoperatively revealed a soft tissue mass suspected to be a desmoid tumor, and the patient is currently being followed up in the outpatient clinic. These cases emphasize the importance of genetic testing in the clinical management of FAP to ensure an accurate diagnosis and differentiation from related syndromes. Although APC mutations are detected in only 20–40% of patients undergoing genetic testing for FAP, APC mutation-negative cases are reported to have a milder phenotype. However, its genetic characteristics remain unclear. The role of SMAD9 mutations is not yet fully understood, but identifying such mutations may deepen our understanding of genetic associations in colorectal polyposis syndromes.