Fanconi Anaemia is a rare autosomal recessive cancer predisposing disorder affecting about 150 or more families in the UK (the true extent is unknown) manifested by: (1) a variable presence of congenital anomalies in up to 70% (e.g., thumb and kidney abnormalities); (2) progressive bone marrow failure in childhood usually leading to haematopoietic stem cell transplantation (80% chance); and (3) a predisposition to acute myeloid leukaemia (10% chance), and in particular oropharyngeal/anogenital squamous cell carcinoma in early adulthood (almost universal in post-haematopoietic stem cell transplant survivors).
There are 13 genetic subgroups reflecting 13 different proteins that can be potentially affected in the Fanconi pathway, an emerging DNA housekeeping mechanism. Some of these genetic subgroups have additional issues such as subgroup FancD1, where affected children are at high risk of brain medulloblastoma and renal Wilm’s tumour. Some FA genetic subgroup heterozygotes/‘carriers’ are also at increased risk of malignancy. BRCA1, one of the ‘breast cancer genes’ is actually part of the Fanconi pathway. A FancD1-affected child is where both parents are heterozygotes for BRCA1 with resultant increased breast cancer risk for the mother.
Further information can be found in the UK and Ireland Fanconi Anaemia Clinical Network’s Standards of Care for Fanconi Anaemia affected Individuals and their Families document
The equivalent US document is published by the Fanconi Anemia Research Fund: Fanconi Anemia: Guidelines for Diagnosis and Management, Fourth Edition, 2014