What are the symptoms? The problems associated with FA include: congenital birth defects: the most common problems affect the thumb and radius (a bone in the lower arm). Other areas often affected are the heart, genitourinary system, other limbs and skin (with abnormal pigmentation – colouring of the skin)growth: short stature is common. Although deficiency of growth and thyroid hormones are seen in FA, their relevance to poor growth is not well understood.low blood cell counts (white cell, red cell and platelet counts): red blood cells carry oxygen around the body, white blood cells fight off infection and platelets help the blood clot. These often fall with age in FA leading to increased infections, anaemia and tiredness, and excessive bruising or bleeding. Many of those with abnormal blood counts during childhood will go on to develop aplastic anaemia.acute myeloid leukaemia (AML; see entry Leukaemia and other Allied Blood disorders) may occur, particularly during the second decade of lifepredisposition to cancer: many types of cancer are more frequent but the commonest complications are the development of acute myeloid leukaemia and head and neck or gynaecological cancers. Bone marrow changes, including the development of ‘clones’ of cells with chromosome changes or myelodysplastic syndrome, often occur before leukaemia develops. What are the causes? FA is an inherited genetic condition. Scientists have now discovered 15 FA or FA-like genes [A, B, C, D1 (BRCA2), D2, E, F, G, I, J, L, M, N, P and RAD51C]. These genes account for more than 95 per cent of FA cases. Some patients do not appear to have mutations in any of the 15 genes, suggesting that more genes are to be discovered. How is it diagnosed? Physical problems present at birth may indicate FA. However, sometimes AML is the first sign of the condition. Blood tests will reveal low counts of red and white cells and platelets. The main diagnostic test for FA is called a chromosome breakage test: in which a patient’s DNA is placed in a test tube with a chemical that damages it. Normal cells are able to correct most of the damage, whereas cells from somebody with FA are significantly damaged. How is it treated? Some abnormalities, particularly abnormal thumbs or skin tags, or heart defects, may require surgery. Aplastic anaemia often responds to administration of the androgenic steroids oxymetholone or Danazol, although the beneficial effect is not permanent and side effects are common. Bone marrow transplantation can cure blood problems, but there can be severe complications. The best results have been in children with tissue-matched sibling donors who are themselves free of the condition. However, results from matched unrelated donors are improving. There is also ongoing research into whether gene therapy can play a role in future treatment. Regular examinations are necessary to watch for signs of leukaemia or cancer. Inheritance patterns and prenatal diagnosis Inheritance patternsAutosomal recessive (98 per cent) or X-linked (2 per cent, in patients with Fanconi B mutations). For autosomal recessive diseases, if both parents carry a mutation in the same FA gene there is a 25 per cent chance that their child will have the condition. Prenatal diagnosisIdentification of the causative gene offers the possibility of prenatal diagnosis in future pregnancies. Cells from the developing baby may be gathered by amniocentesis or chorionic villus sampling and molecular (DNA) testing carried out to look for the mutation. Some parents have chosen to combine preimplantation diagnosis with tissue typing of embryos so that the cord blood from a healthy baby can be used for transplantation of a sibling with aplastic anaemia. Is there support? Fanconi Hope Tel: 0845 271 2811Email: via websiteWebsite: fanconihope.org The Group is a Registered Charity in England and Wales No. 1126894. It provides information and support to families affected by Fanconi anaemia and clinicians with an interest in the condition. The Group supports a UK Fanconi Anaemia National Registry and provides grants for research. Group details last updated August 2014.