Inherited aplastic anaemias/bone marrow failure syndromes

SummaryThe inherited aplastic anaemias/bone marrow (BM) failure syndromes are a heterogeneous group of disorders characterized by BM failure usually in association with one or more somatic abnormality. The BM failure often presents in childhood but this may not be until adulthood in some cases highlighting the need for the adult haematologist to be aware of these disorders. Indeed some patients initially labelled as “idiopathic aplastic anaemia” are cryptic presentations of these genetic syndromes. Since 1992, when the first Fanconi anaemia (FA) gene was cloned there have been considerable advances in the genetics of these syndromes. These advances are beginning to provide a better understanding of normal haemopoiesis and how this might be disrupted in patients with BM failure. They have also provided important insights into some fundamental biological pathways: DNA repair-FA/BRCA pathway; telomere maintenance- dyskeratosis congenita related genes; ribosome biogenesis-Shwachman Diamond syndrome and Diamond-Blackfan anaemia genes. Additionally, as these disorders are usually associated with developmental abnormalities and an increased risk of cancer they are providing new insights into human development and the genesis of cancer. These advances have led to improved diagnosis of patients with these disorders. They may now also provide the platform for developing new treatments.