PURPOSE OF REVIEW: Severe congenital neutropenia has been a well known 
hematological condition for over 50 years. Over this long period of time, the 
variable genetic causes and associated sequelae of the disease have been 
ascertained, and successful treatment strategies developed. Over the past 2 
years, however, new studies have added greatly to our understanding of the 
molecular basis of the disease, details of which are presented in this review.
RECENT FINDINGS: Recent studies have elucidated a role for the unfolded protein 
response in mediating the pathogenic effects of ELA2 mutations, the most common 
mutation in severe congenital neutropenia (SCN) as well as cyclic neutropenia. 
Genetic lesions in HAX1 have also been identified in the original Kostmann 
pedigree representing the autosomal recessive form of SCN. An emerging theme is 
the convergence of these and other genetic lesions underlying SCN in enhancing 
neutrophil apoptosis. Other studies have revealed the importance of multiple 
independent mutations in these and other genes in SCN. Finally, the key role for 
signal transducer and activator of transcription 5 in mediating the effects of 
granulocyte colony-stimulating factor receptor truncation mutations in the 
development of myelodysplastic syndrome/acute myeloid leukemia following SCN has 
been elucidated.
SUMMARY: As the full spectrum of molecular mutations causing neutropenia 
emerges, it is becoming possible to differentiate patients into subtypes with 
different prognoses, for whom tailored therapies are indicated.