What Causes Severe Congenital Neutropenia
Changes (mutations) in different genes can cause severe congenital neutropenia. The changes can:
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Affect a person’s bone marrow, causing the bone marrow to make neutrophils that do not work correctly or have a shorter-than-normal life span.
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Cause proteins to build up inside the neutrophils, so the cells die.
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Prevent the neutrophils from maturing properly.
It is important for your child’s care team to understand genetic reason for your child’s severe congenital neutropenia. Two specific genetic changes are the primary causes of SCN.
- An estimated 50% of severe congenital neutropenia changes happen in the ELANE gene.
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About 10% of the changes occur in the HAX1 gene.
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Other genes linked to severe congenital neutropenia include: CSF3R, G6PC3, GFI1, X-linked WAS, CXCR4, VPS45A and JAGN1.
A change in the ELANE gene is an autosomal dominant genetic mutation.
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"Autosomal" is a change that occurs in the non-sex chromosomes.
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“Dominant” means that a child only needs one copy of the changed gene to have this type of condition. The copy of the gene can come from either parent.
- When a child inherits an autosomal dominant change, this indicates that only one of the parents has the genetic change.
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If only one parent has this change, then there is a 50% chance that their child will have the genetic condition.
A change in the HAX1 gene is an autosomal recessive genetic mutation.
- “Recessive” indicates that a child gets two copies of the changed gene (one from each parent).
- When a child inherits an autosomal recessive change, this shows that the parents are both carriers of the change.
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If both parents are carriers, then there is a 25% chance that the child will have the condition.
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However, the carrier parents usually do not have symptoms of the condition.
Rarely, a child may inherit a genetic change in an X-linked recessive pattern.
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“X-linked recessive” means that the gene is on the X chromosome (one of two sex chromosomes). For example, X-linked WAS is one gene inherited through this pattern.
- Since males have one X chromosome and one Y chromosome, a genetic change in their X chromosome is enough for them to have severe congenital neutropenia.
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Since females have two X chromosomes, they would need to have changes in both to have severe congenital neutropenia.
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Because of this inheritance pattern, males are more likely to have severe congenital neutropenia.
About 33% of people with severe congenital neutropenia do not have a known genetic change. It is not clear why they have the condition.
Most people with SCN do not have a family history of the disease.
