Severe congenital neutropenia (CN) includes a variety of hematologic disorders 
characterized by severe neutropenia, with absolute neutrophil counts (ANC) below 
0.5 x 10(9)/L, and associated with severe systemic bacterial infections from 
early infancy. One subtype of CN, Kostmann syndrome, is an autosomal recessive 
disorder, characterized histopathologically by early-stage maturation arrest of 
myeloid differentiation. CN with similar clinical features occurs as an 
autosomal dominant disorder and many sporadic cases also have been reported. 
This genetic heterogeneity suggests that several pathophysiological mechanisms 
may lead to this common clinical phenotype. Recent studies on the genetic bases 
of CN have detected inherited or spontaneous point mutations in the neutrophil 
elastase gene (ELA 2) in about 60% to 80% of patients and, less commonly, 
mutations in other genes. Acquisition of additional genetic defects during the 
course of the disease, for example, granulocyte colony-stimulating factor 
(G-CSF) receptor gene mutations and cytogenetic aberrations, indicates an 
underlying genetic instability as a common feature for all congenital 
neutropenia subtypes. Data on more than 600 patients with CN collected by the 
Severe Chronic Neutropenia International Registry (SCNIR) demonstrate that, 
regardless of the particular CN subtype, more than 95% of these patients respond 
to recombinant human (rHu)G-CSF with ANCs that can be maintained above 1.0 x 
10(9)/L. Adverse events include mild splenomegaly, osteoporosis, and malignant 
transformation into myelodysplasia (MDS)/leukemia. If and how G-CSF treatment 
impacts on these adverse events is not fully understood. In recent analyses the 
influence of the G-CSF dose required to achieve neutrophil response (ANC 
>1,000/microL) in the risk of developing acute myeloid leukemia (AML) has been 
reported. Hematopoietic stem cell transplantation (HSCT) is still the only 
treatment available for patients who are refractory to G-CSF treatment.