Bone marrow failure syndromes, a practical approach to diagnosis

The inherited bone marrow failure (IBMF) syndromes are a heterogeneous group of disorders with characteristic quantitative or qualitative abnormalities affecting one or more hematopoietic lineages. IBMF syndromes are due to germline mutations affecting structural proteins or key cellular pathways such as DNA repair, telomerase biology, and ribosomal biosynthesis. These mutations lead to single or multiple peripheral blood cytopenias that either result from an absence of one or more lineages of hematopoietic progenitors in the marrow or to an increase cell death of one or more marrow progenitor lineages. Most IBMF syndromes manifest in childhood, but some are recognized later in life depending on the severity of symptoms. This review we will summarize the clinical presentation, diagnostic findings, and genetic findings of the most frequent and best studied IBMF syndromes with a special focus on the diagnostic dilemmas which can occur during the work up of a child with suspected a IBMF syndrome.