Genetic testing in Kostman’s Syndrome and cyclical neutropenia – pro
Kostmann syndrome is a group of diseases that affect myelopoiesis, causing a congenital form of neutropenia (severe congenital neutropenia [SCN]), usually without other physical malformations. SCN manifests in infancy with life-threatening bacterial infections.
Most cases of SCN responds to treatment with granulocyte colony-stimulating factor (filgrastim), which increases the neutrophil count and decreases the severity and frequency of infections. Although this treatment has significantly improved survival, people with SCN are at risk of long-term complications such as hematopoietic clonal disorders (myelodysplastic syndrome, acute myeloid leukemia).
Various types of Kostman’s Syndrome have been described. Some of them have ELANE (formerly ELA2) gene on chromosome 19p13.3, which encodes neutrophil elastase. Over a hundred ELANE mutations have been found in SCN1. This same gene is mutated in cyclic neutropenia. Other mutations as well have been reported in other sybtypes.
There are no guidelines or studies that recommend genetic testing, becsue it is not clear how knowing the mutation affects clinical approach.
Cornelia Zeidler, Manuela Germeshausen, Christoph Klein and Karl Welte, Clinical implications ofELA2-,HAX1-, and G-CSF-receptor(CSF3R) mutations in severe congenital neutropenia. British Journal of Haematology Volume 144, Issue 4, Version of Record online: 17 DEC 2008
Jean Donadieu et al, Congenital neutropenia: diagnosis, molecular bases and patient management. Orphanet Journal of Rare Diseases20116:26
Jacobson CA, Berliner N. Neutropenia. Greer JP, Arber DA, Glader B, et al, eds. Wintrobe’s Clinical Hematology. 13th ed. Philadelphia, PA: Lippincott, Williams & Wilkins; 2014. 1279-89.