Autosomal dominant severe congenital neutropenia

Autosomal dominant severe congenital neutropenia (SCN) is a rare inherited disorder of the blood and immune system characterized by persistently very low levels of neutrophils (a type of white blood cell essential for fighting bacterial and fungal infections) from birth or early infancy. The most common genetic cause of the autosomal dominant form is mutations in the ELANE gene (encoding neutrophil elastase), though mutations in other genes such as GFI1 and CSF3R have also been implicated. Patients typically present in the neonatal or early infantile period with recurrent, severe, and potentially life-threatening bacterial infections, including skin infections (cellulitis, abscesses), oral ulcers, gingivitis, stomatitis, pneumonia, and deep-seated infections such as liver abscesses or septicemia. Bone marrow examination characteristically shows a maturation arrest of myeloid precursors at the promyelocyte/myelocyte stage. The condition was historically known as Kostmann syndrome, although that term originally referred to the autosomal recessive form. Severe congenital neutropenia is now recognized as a genetically heterogeneous group of disorders, with the autosomal dominant ELANE-related form being the most prevalent subtype. Absolute neutrophil counts are typically below 200 cells per microliter of blood. Without treatment, affected individuals are at high risk of fatal infections in early childhood. The primary treatment is recombinant human granulocyte colony-stimulating factor (G-CSF, filgrastim), which is effective in raising neutrophil counts and reducing infection frequency in the majority of patients. Most patients require lifelong G-CSF therapy. However, a significant concern is the long-term risk of developing myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML), which occurs in approximately 15–20% of patients over time, often associated with acquired mutations in the CSF3R gene. Hematopoietic stem cell transplantation (HSCT) remains the only curative option and is considered for patients who are refractory to G-CSF therapy or who develop malignant transformation.

Common questions about Autosomal dominant severe congenital neutropenia