Fanconi anaemia

The estimated prevalence is 1/143,000-1/250,000, based on European registry live-birth data.

Fanconi anaemia is inherited in an autosomal recessive manner in nearly all genetic subtypes; FANCB-related FA is X-linked and RAD51-related FA is autosomal dominant. For autosomal recessive subtypes, parents of an affected individual are obligate heterozygotes and the recurrence risk for siblings of an affected proband is 25%. Prenatal molecular testing is technically possible once the familial pathogenic variants have been identified.

Diagnosis is established by demonstration of increased chromosome breakage and radial forms on cytogenetic testing of peripheral-blood lymphocytes exposed to diepoxybutane (DEB) or mitomycin C (MMC) and/or molecular genetic testing for pathogenic variants in one of the 23 genes known to cause FA.

Main differential diagnoses include:

• Nijmegen breakage syndrome: progressive microcephaly, early growth deficiency that improves with age, recurrent respiratory infections, increased lymphoma risk, and premature ovarian failure; cells may show increased chromosome breakage with MMC; NBN
• Bloom syndrome: severe pre- and postnatal growth deficiency, immune abnormalities, photosensitivity, insulin resistance, and high early-age cancer risk; cells show high rates of spontaneous chromosome breakage; BLM
• Seckel syndrome: growth deficiency, microcephaly with intellectual disability, and characteristic facial appearance; cells may show increased chromosome breakage with DNA cross-linking agents and may be associated with pancytopenia/AML; ATR, CENPJ, CEP152, and others

• Establishing the molecular diagnosis confirms the clinical suspicion and clarifies the underlying genetic cause.
• The molecular diagnosis is a prerequisite for specific and individualised surveillance and clinical management, which are determined by the treating physicians in consultation with the affected individual.
• Once the familial pathogenic variants have been identified, predictive and carrier testing of at-risk relatives becomes technically possible.

• Mehta PA, Ebens CL. Fanconi anemia. 2002 Feb 14 [updated 2026 Jan 15]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews^® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2026. PMID: 20301575.
• Anurogo D, Yuli Prasetyo Budi N, Thi Ngo MH, Huang YH, Pawitan JA. Cell and gene therapy for anemia: hematopoietic stem cells and gene editing. Int J Mol Sci. 2021;22(12):6275. PMID: .