Fanconi anaemia: A syndrome with distinct subgroups

Br J Haematol. 2022 May;197(4):467-474. doi: 10.1111/bjh.18091. Epub 2022 Feb 22.


Fanconi anaemia (FA) is an inherited bone marrow failure syndrome (IBMFS) with a high cancer predisposition rate. Traditional diagnoses are made before age 10 years due to bone marrow failure (BMF) and characteristic birth defects. Up to 10% of published cases were adults at diagnosis. We hypothesized that FA subgroups diagnosed in childhood are distinct from those diagnosed as adults. We classified patients by age at diagnosis of FA as FA-PED (<18 years) or FA-ADULT (≥18 years). The National Cancer Institute IBMFS cohort included 178 FA-PED and 26 FA-ADULT cases. We compared various features; the cumulative incidences of first adverse events (severe BMF leading to haematopoietic cell transplant or death, leukaemia, or solid tumours) were compared using competing-risk analyses. FA-ADULT lacked the 'typical' FA features (birth defects and early-onset BMF or leukaemia), were mainly female, had more patients with FANCA genotype, and had or developed more head and neck squamous-cell carcinoma (HNSCC) and/or gynaecological cancers compared with FA-PED, albeit at similar ages in both subgroups. FA-ADULT is a distinct subgroup that remained unrecognized during childhood. Centres for adult haematology-oncology should consider FA diagnosis in patients with early-onset HNSCC or gynaecological cancer with or without haematologic problems.

Keywords: Fanconi anaemia; cancer predisposition; gynaecological cancer; head and neck squamous-cell carcinoma; inherited bone marrow failure.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Bone Marrow Failure Disorders
  • Child
  • Congenital Bone Marrow Failure Syndromes
  • Fanconi Anemia* / complications
  • Fanconi Anemia* / diagnosis
  • Fanconi Anemia* / genetics
  • Female
  • Head and Neck Neoplasms*
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Leukemia*
  • Squamous Cell Carcinoma of Head and Neck