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Catastrophic chemotherapy toxicity leading to diagnosis of Fanconi anaemia due to FANCD1/BRCA2 during adulthood: description of an emerging phenotype
  1. Emilia Ip1,
  2. Catriona McNeil2,3,
  3. Peter Grimison2,
  4. Tahlia Scheinberg2,3,4,
  5. Emma Tudini5,
  6. Gladys Ho6,7,
  7. Rodney J Scott8,9,10,
  8. Christina Brown11,
  9. Charbel Sandroussi12,
  10. Pascale Guitera3,13,14,
  11. Amanda B Spurdle5,
  12. Annabel Goodwin15,16
  1. 1 Cancer Genetics, Liverpool Hospital, Sydney, New South Wales, Australia
  2. 2 Medical Oncology, Chris O'Brien Lifehouse, Camperdown, New South Wales, Australia
  3. 3 Department of Medicine, The University of Sydney, Sydney, New South Wales, Australia
  4. 4 Clinical Prostate Cancer Group, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
  5. 5 Department of Genetics and Computational Biology, Queensland Institute of Medical Research, Brisbane, Queensland, Australia
  6. 6 Western Sydney Genetics Program, Children's Hospital at Westmead, Westmead, New South Wales, Australia
  7. 7 Discipline of Paediatrics and Child Health, University of Sydney, Sydney, New South Wales, Australia
  8. 8 Division of Molecular Medicine, NSW Health Pathology, Newcastle, New South Wales, Australia
  9. 9 School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, New South Wales, Australia
  10. 10 Hunter Medical Research Institute, New Lambton, New South Wales, Australia
  11. 11 Haematology Unit, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
  12. 12 Department of Hepatobiliary and Upper Gastrointestinal Surgery, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
  13. 13 Melanoma Institute Australia, North Sydney, New South Wales, Australia
  14. 14 Dermatology, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
  15. 15 Cancer Genetics, Royal Prince Alfred Hospital, Camperdown, New South Wales, Australia
  16. 16 Medical Oncology, Concord Repatriation General Hospital, Concord, New South Wales, Australia
  1. Correspondence to Dr Annabel Goodwin, Cancer Genetics, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia; annabel.goodwin{at}


Fanconi anaemia due to biallelic loss of BRCA2 (Fanconi anaemia subtype D1) is traditionally diagnosed during childhood with cancer rates historically reported as 97% by 5.2 years. This report describes an adult woman with a history of primary ovarian failure, who was diagnosed with gastrointestinal adenocarcinoma and BRCA2-associated Fanconi anaemia at 23 years of age, only after she suffered severe chemotherapy toxicity. The diagnostic challenges include atypical presentation, initial false-negative chromosome fragility testing and variant classification. It highlights gastrointestinal adenocarcinoma as a consideration for adults with biallelic BRCA2 pathogenic variants with implications for surveillance. After over 4 years, the patient has no evidence of gastrointestinal cancer recurrence although the tumour was initially considered only borderline resectable. The use of platinum-based chemotherapy, to which heterozygous BRCA2 carriers are known to respond, may have had a beneficial anticancer effect, but caution is advised given its extreme immediate toxicity at standard dosing. Fanconi anaemia should be considered as a cause for women with primary ovarian failure of unknown cause and referral to cancer genetic services recommended when there is a family history of cancer in the hereditary breast/ovarian cancer spectrum.

  • genetic testing
  • medical oncology
  • phenotype
  • gastrointestinal diseases
  • genetic predisposition to disease

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  • Contributors AG, CM, PGr, TS, CB, CS and PGu provided clinical care to the individual described in this report and input regarding the case description and ongoing management. ET, GH, RJS and ABS provided important input regarding variant classification and laboratory diagnostics. EI was responsible for the initial manuscript draft and ongoing revisions. All authors reviewed the manuscript, provided critical review and approved the final manuscript.

  • Funding EI received funding from a Fellowship grant from the Cancer Institute, NSW (ID 2018_03). TS received funding support from Sydney Catalyst, University of Sydney, NSW, Australia and Cancer Institute, NSW. ABS is support by an NHMRC Investigator Fellowship (ID 1177524).

  • Competing interests All authors have completed a conflict of interest disclosure form, with the following disclosures to be reported: TS received a conference travel grant from AstraZeneca and AG has been on advisory boards for AstraZeneca (May 2018) and Pfizer (November 2018) and has presented to a Pharmaceutical Benefits Advisory Committee regarding talazoparib (Pfizer) in November 2019.

  • Provenance and peer review Not commissioned; externally peer reviewed.