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Severe congenital neutropenia

Severe congenital neutropenia

Reviewed April 2010

What is severe congenital neutropenia?

Severe congenital neutropenia is a condition that causes affected individuals to be prone to recurrent infections. People with this condition have a shortage (deficiency) of neutrophils, a type of white blood cell that plays a role in inflammation and in fighting infection. The deficiency of neutrophils, called neutropenia, is apparent at birth or soon afterward. It leads to recurrent infections beginning in infancy, including infections of the sinuses, lungs, and liver. Affected individuals can also develop fevers and inflammation of the gums (gingivitis) and skin. Approximately 40 percent of affected people have decreased bone density (osteopenia) and may develop osteoporosis, a condition that makes bones progressively more brittle and prone to fracture. In people with severe congenital neutropenia, these bone disorders can begin at any time from infancy through adulthood.

Approximately 20 percent of people with severe congenital neutropenia develop cancer of the blood-forming tissue (leukemia) or a disease of the blood and bone marrow (myelodysplastic syndrome) during adolescence.

Some people with severe congenital neutropenia have additional health problems such as seizures, developmental delay, or heart and genital abnormalities.

How common is severe congenital neutropenia?

The incidence of severe congenital neutropenia is estimated to be 1 in 200,000 individuals.

What genes are related to severe congenital neutropenia?

Severe congenital neutropenia can result from mutations in at least five different genes. These genes play a role in the maturation and function of neutrophils, which are cells produced by the bone marrow. Neutrophils secrete immune molecules and ingest and break down foreign invaders.

Gene mutations that cause severe congenital neutropenia lead to the production of neutrophils that die off quickly or do not function properly. Some gene mutations result in unstable proteins that build up in neutrophils, leading to cell death. Other gene mutations result in proteins that impair the maturation or function of neutrophils, preventing these cells from responding appropriately to immune signals.

About half of all cases of severe congenital neutropenia are caused by mutations in the ELANE gene. Another 15 percent are caused by mutations in the HAX1 gene. The other genes each account for only a small percentage of all cases of this condition. In about one-third of people with severe congenital neutropenia, the cause of the disorder is unknown.

Read more about the ELANE and HAX1 genes.

See a list of genes associated with severe congenital neutropenia.

How do people inherit severe congenital neutropenia?

Most cases of severe congenital neutropenia are classified as sporadic and occur in people with no apparent history of the disorder in their family. Some of these cases are associated with changes in specific genes; however in some cases the cause of the disorder is unknown.

Many cases of severe congenital neutropenia are inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Less often, this condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

In rare cases, severe congenital neutropenia is inherited in an X-linked recessive pattern. In these cases, the gene that causes the condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Where can I find information about diagnosis or management of severe congenital neutropenia?

Where can I find additional information about severe congenital neutropenia?

You may find the following resources about severe congenital neutropenia helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for severe congenital neutropenia?

  • congenital agranulocytosis
  • congenital neutropenia
  • infantile genetic agranulocytosis
  • Kostmann disease
  • Kostmann's agranulocytosis
  • Kostmann's syndrome
  • severe infantile genetic neutropenia

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about severe congenital neutropenia?

Where can I find general information about genetic conditions?

What glossary definitions help with understanding severe congenital neutropenia?

References (11 links)


The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.

Reviewed: April 2010
Published: February 1, 2016