Fanconi anaemia: A syndrome with distinct subgroups

Abstract

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.

FANCA c.3624C&gt;T (p.Ser1208=) is a hypomorphic splice variant associated with delayed onset of Fanconi anemia

“…The median age at diagnosis was 28 years (range, 11-63 years), whereas a typical FA diagnosis occurs at a median age of 10 years. 28 , 29 The cross-link–induced breaks per metaphase in 4 individuals were <3, and individual 6 displayed only 0.1 breaks per metaphase, even below the number required for FA diagnosis. Individual 6 was diagnosed at age 63 years, after developing MDS.…”