Fanconi-Like Syndrome with Negative Chromosomal Breakages Test and High Incidence of Myelodysplasia.

Fanconi’s anaemia (FA) is a syndrome of defective chromosomal repair characterised by bone marrow failure, skeletal and visceral abnormalities, progression to myelodysplasia (MDS) and acute myeloid leukaemia (AML), hypersensitivity to alkylating agents and increased chromosomal breakage using diepoxybutane (DEB) testing. We describe 13 patients who presented with FA like clinical and/or haematological features who had negative DEB testing. There were 9 males and 4 females with an average age of presentation of 23 years (range 1.5 months - 53 years). They had isolated neutopenia (1/13) or anaemia (1/13), bicytopenia (4/13) or pancytopenia (7/13) at first presentation. Haemoglobin level ranged between 3.8 - 15 g/dl (mean 9.7), white cell count 0.64 - 8.4 × 10⁹/l (mean 2.88), neutrophils 0.05 - 5.43 × 10⁹/l (mean 1.14) and platelets 30 - 179 ×10⁹/l (mean 82). Five patients had macrocytosis with mean cell volume (MCV) above 100fl. The most common morphological features noticed were high arched palate, short stature and short fingers and toes. Seven patients had hypocellular marrow with trilineage dysplasia (refractory anaemia), one had hypocellular marrow with refractory anaemia with ring sideroblasts, 3 patients had hypocellular marrow and AML and 2 had hypocellular marrow with no morphological dysplasia. DEB testing for increased chromosomal breaks was negative in all the 13 patients. Nine patients had cytogenetic abnormalities with monosomy 7 or complex abnormalities being the most common. Three patients have stable blood counts on a watch and wait policy 6–24 months from diagnosis. Five patients’ cytopenias progressed responding to treatment with androgens (2) and anti-thymocyte globulin with steroids (1) and 2 required allogeneic stem cell transplantation (BMT). Androgen responses were sustained in one patient for over 12 years and was followed by AML transformation in the other. Two patients are lost to follow up, 1 died following BMT for AML and 2 had severe mucositis with AML therapy fatal in one and associated with prolonged pancytopenia in another. Four patients had BMT, 2 are in remission, 1 died post BMT and 1 failed. FA phenotype with cytopenia and subsequent progression to MDS/AML is well known and diagnosis is usually confirmed with DEB testing. It is important, however, to recognise FA like syndromes with negative DEB, who appear to have similar clinical behaviour and sensitivity to chemotherapy, as therapy may differ from standard cases of aplastic anaemia, MDS or AML. Genetic testing for the described Fanconi genes may shed more light into those cases.