What genetic mutation is most likely underlying in a 70-year-old woman with a family history of (Breast Cancer) maternal breast cancer, paternal (Melanoma) melanoma and (Prostate Cancer) prostate cancer, and a maternal aunt with a history of (Ovarian Cancer) ovarian cancer, presenting with bloating, increased urinary frequency, and dull abdominal pain radiating to the pelvis?

Differential Diagnosis

The patient's presentation of bloating, increased urinary frequency, dull abdominal pain radiating to the pelvis, and a significant family history of cancers suggests an underlying genetic predisposition to cancer. The differential diagnosis can be organized into the following categories:

• Single Most Likely Diagnosis

  • BRCA1 and BRCA2: The patient's family history of breast, ovarian, and other cancers (maternal breast cancer, paternal melanoma and prostate cancer, and a maternal aunt with ovarian cancer) is highly suggestive of a hereditary breast and ovarian cancer (HBOC) syndrome, which is most commonly associated with mutations in the BRCA1 and BRCA2 genes. The patient's symptoms could be indicative of ovarian cancer, which is a common manifestation of BRCA1 and BRCA2 mutations.

• Other Likely Diagnoses

  • APC: Although less likely given the specific family history, mutations in the APC gene are associated with familial adenomatous polyposis (FAP), which increases the risk of colorectal and other cancers. However, the patient's symptoms and family history do not strongly suggest FAP.
  • CDH1: This gene is associated with hereditary diffuse gastric cancer and lobular breast cancer. While it's a possibility, the patient's symptoms and family history do not specifically point towards gastric cancer.

• Do Not Miss Diagnoses

  • These are diagnoses that may not be the most likely but are critical to consider due to their potential severity and impact on management:
    • Ovarian Cancer: Regardless of the genetic mutation, the patient's symptoms could be indicative of ovarian cancer, which is often diagnosed at a late stage. It's crucial to investigate this possibility thoroughly.
    • Colorectal Cancer: Although the patient denies blood in the stool or bowel movement irregularity, colorectal cancer can present with abdominal pain and should be considered, especially given the family history of various cancers.

• Rare Diagnoses

  • DHQ2 and DHQ8: These are not commonly recognized genes associated with the patient's presentation or family history of cancer.
  • FAS and FASL: These genes are involved in the regulation of apoptosis and are not directly linked to the patient's symptoms or the specific pattern of family cancer history described.
  • Other rare genetic syndromes could be considered, but they would be less likely given the information provided and would typically involve more specific and distinctive clinical features or family histories.