Article Text

Download PDFPDF
Discerning clinicopathological features of congenital neutropenia syndromes: an approach to diagnostically challenging differential diagnoses
  1. Xenia Parisi1,
  2. Jacob R Bledsoe2
  1. 1Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
  2. 2Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA
  1. Correspondence to Dr Jacob R Bledsoe, Pathology, Boston Children's Hospital, Boston, Massachusetts, USA; jacob.bledsoe{at}


The congenital neutropenia syndromes are rare haematological conditions defined by impaired myeloid precursor differentiation or function. Patients are prone to severe infections with high mortality rates in early life. While some patients benefit from granulocyte colony-stimulating factor treatment, they may still face an increased risk of bone marrow failure, myelodysplastic syndrome and acute leukaemia. Accurate diagnosis is crucial for improved outcomes; however, diagnosis depends on familiarity with a heterogeneous group of rare disorders that remain incompletely characterised. The clinical and pathological overlap between reactive conditions, primary and congenital neutropenias, bone marrow failure, and myelodysplastic syndromes further clouds diagnostic clarity.

We review the diagnostically useful clinicopathological and morphological features of reactive causes of neutropenia and the most common primary neutropenia disorders: constitutional/benign ethnic neutropenia, chronic idiopathic neutropenia, cyclic neutropenia, severe congenital neutropenia (due to mutations in ELANE, GFI1, HAX1, G6PC3, VPS45, JAGN1, CSF3R, SRP54, CLPB and WAS), GATA2 deficiency, Warts, hypogammaglobulinaemia, infections and myelokathexis syndrome, Shwachman-Diamond Syndrome, the lysosomal storage disorders with neutropenia: Chediak-Higashi, Hermansky-Pudlak, and Griscelli syndromes, Cohen, and Barth syndromes. We also detail characteristic cytogenetic and molecular factors at diagnosis and in progression to myelodysplastic syndrome/leukaemia.

  • Hematology
  • Bone Marrow Diseases

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.


  • Handling editor Vikram Deshpande.

  • X @XeniaParisi

  • Contributors XP and JRB both contributed significantly to the conceptualisation and writing of this manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests JRB serves as a consultant for X4 Pharmaceuticals and has a research agreement with X4 Pharmaceutical on flow cytometric features of neutropenia syndromes.

  • Provenance and peer review Commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.