Hyperinsulinism (HI) is a disease in which the body makes too much insulin. HI can occur spontaneously or be inherited, meaning it is passed down from the parents to their children.  

Parents pass down traits to their children through things called genes. Genes give directions to build the whole body, and most genes come in pairs. This means that there are two copies of each gene. A child inherits one copy of each gene from their mother and the other copy from their father.

Below you’ll find information on the most common ways HI can be inherited.

Autosomal Dominant Inheritance

In autosomal dominant inheritance, one copy of a gene pair changes. “Dominant” indicates that this single change in the gene is enough to cause HI. Often a parent with a dominant gene change also has HI.

For a parent with an autosomal dominant gene change, each of their children has a 50% chance to have HI.  

Autosomal Recessive Inheritance

Autosomal recessive inheritance happens when a child receives an altered copy of a gene from each parent. Neither copy of the gene works in the child, causing them to have HI.  

While both parents are carriers of the altered gene, in autosomal recessive inheritance, they do not have HI because each parent also has a working copy of the gene.

For these parents, each of their children has a 25% chance to have HI.

De Novo (New) Genetic Changes

Sometimes a genetic change occurs spontaneously, meaning it was not inherited from either parent.

When this happens, it’s important to remember that it happened by chance and was not caused by anything either parent did or did not do before or during pregnancy.

For parents whose child has HI due to a new genetic change, each of their future children has a less than 1% chance to have HI.

Focal HI

Focal HI occurs by chance during pregnancy:

1. The father passes down an altered gene, and the mother passes down a normal copy of the gene.

2. In a small spot inside the pancreas of the fetus, the normal gene is lost.

3. The altered gene is duplicated and there are no normal copies of the gene in that spot in the pancreas.

4. A focal lesion forms, causing focal HI in the child.

When this happens, it’s important to remember that it happened by chance and was not caused by anything either parent did or did not do before or during pregnancy. 

When the father passes down the altered gene in a pregnancy, the chance of focal HI happening in that pregnancy is less than 0.5%.

The causes of HI inheritance are complex, and it’s often best to discuss these things with an expert. At CHOP, we offer access to world-class doctors ready to support you, your children and your family as you come to understand a diagnosis like HI.