What Is Severe Congenital Neutropenia?

Severe congenital neutropenia (SCN) is a rare genetic condition that increases a child’s risk of having frequent infections. “Congenital” means present at birth. “Neutropenia” means having low levels of a type of white blood cells called neutrophils. White blood cells are important for fighting infections in the body. The lower the level of neutrophils in the body, the higher the risk for infections.

About one in every 200,000 people has severe congenital neutropenia. The condition is more common in males than in females.

Severe Congenital Neutropenia Causes

Changes (mutations) in different genes can cause severe congenital neutropenia. The changes can:

• 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.
• Cause proteins to build up inside the neutrophils, so the cells die.
• 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.
• About 10% of the changes occur in the HAX1 gene.
• 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.

• "Autosomal" is a change that occurs in the non-sex chromosomes.
• “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.
• 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.
• If both parents are carriers, then there is a 25% chance that the child will have the condition.
• 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.

• “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.
• Since females have two X chromosomes, they would need to have changes in both to have severe congenital neutropenia.
• 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.

Severe Congenital Neutropenia Symptoms

The signs of severe congenital neutropenia often become evident early in life. People with SCN experience frequent infections, most often in the mouth, throat, sinuses, skin and lungs. They may have frequent fevers as well.

People with SCN also can experience problems such as:

• Osteopenia (low bone density)
• Osteoporosis (weak and brittle bones)
• Seizures
• Developmental delays
• Genital and heart abnormalities

Children who have severe congenital neutropenia have a higher risk of developing blood cancers. These cancers include myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) and other types of leukemia.

Severe Congenital Neutropenia Diagnosis

Usually, severe congenital neutropenia is diagnosed soon after birth. The diagnosis of SCN starts with a physical exam and symptom check. Blood tests that include a full blood count can determine the number of neutrophils. A physician also may order bone marrow testing.

Genetic testing can show mutations in a child’s genes. Parents also can have genetic testing to see if they are carriers of these genetic mutations.

Severe Congenital Neutropenia Treatment

Treatment for severe congenital neutropenia focuses on preventing and managing infections.

Treatment may include:

• Antibiotics
• Anti-inflammatory drugs
• Granulocyte-colony stimulating factor (G-CSF) to treat low white blood cell count
• Bone marrow transplants

Severe Congenital Neutropenia Long-Term Outlook

Children with SCN may need frequent doctor visits including blood and bone marrow tests to monitor their health and receive treatments. Children who receive high-quality care for severe congenital neutropenia can lead healthy and normal lives.