Definition
An inherited DNA repair disorder causing bone marrow failure, congenital anomalies and cancer predisposition. Thumb and radial anomalies occur in about half of patients.
Aetiology
- Mutations in at least 22 FANC genes
- Autosomal recessive, with FANCB X linked
- Defective repair of DNA interstrand crosslinks
Clinical Features
- Thumb hypoplasia or absence, with or without radial deficiency, see radial club hand
- Short stature, microcephaly and microphthalmia
- Café au lait spots and skin hyperpigmentation
- Renal and genitourinary anomalies
- Marrow failure with pancytopenia, median onset around 7 years
- Raised risk of acute myeloid leukaemia and head and neck cancer
Investigations
- Chromosome breakage test with diepoxybutane or mitomycin C
- Blood film and indices may be normal at birth
- Renal ultrasound and echocardiogram
- Gene panel confirms the complementation group
- 7% of tested children with thumb anomalies were positive in one series, all with other anomalies
Differential Diagnosis
- TAR syndrome
- Holt-Oram syndrome
- VACTERL association
- Diamond-Blackfan anaemia
- Congenital upper limb deficiency
Management
- Screen before limb surgery. Chromosome breakage testing in radial deficiency with other anomalies
- Haematopoietic stem cell transplant. The only cure for marrow failure
- Androgens. Temporary haematological support
- Pollicisation or centralisation. Standard indications once haematology clears surgery
Complications
- Bleeding and infection from pancytopenia around surgery
- Severe toxicity from standard chemotherapy and radiation doses
References
- Auerbach AD. Fanconi anemia and its diagnosis. Mutat Res. 2009, 668(1-2), 4-10. PubMed
- Webb ML, Rosen H, Taghinia A, McCarty ER, Cerrato F, Upton J, Labow BI. Incidence of Fanconi anemia in children with congenital thumb anomalies referred for diepoxybutane testing. J Hand Surg Am. 2011, 36(6), 1052-7. PubMed
Reviewed by Professor Phong Tran, Head of Orthopaedic Surgery, Western Health. Last updated 19 October 2026.