Severe congenital neutropenia

Severe congenital neutropenia
Other names	Kostmann disease, Kostmann's agranulocytosis, Kostmann's syndrome, congenital agranulocytosis, congenital neutropenia, permanent neutropenia, infantile genetic agranulocytosis, severe infantile genetic neutropenia
Specialty	Hematology
Usual onset	Infancy[1]
Types	SCN1-SCN5, SCNX
Causes	Mutation in genes, depending on type[1]
Diagnostic method	Blood test, genetic testing[1]
Treatment	G-CSF, HSCT[1]
Medication	Filgrastim[1]
Frequency	2-3 in million (2018)[1]

Severe congenital neutropenia (SCN), also often known as Kostmann syndrome or disease, is a group of rare disorders that affect myelopoiesis, causing a congenital form of neutropenia, usually without other physical malformations. SCN manifests in infancy with life-threatening bacterial infections.^[2] It causes severe pyogenic infections. It can be caused by autosomal dominant inheritance of the ELANE gene, autosomal recessive inheritance of the HAX1 gene. There is an increased risk of leukemia and myelodysplastic cancers.

Most cases of SCN respond to treatment with granulocyte colony-stimulating factor (filgrastim), which increases the neutrophil count and decreases the severity and frequency of infections.^[2] 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).

Kostmann disease (SCN3), the initial subtype recognized, was clinically described in 1956. This type has an autosomal recessive inheritance pattern, whereas the most common subtype, SCN1, shows autosomal dominant inheritance.