Congenital adrenal hyperplasia (CAH) affects the adrenal glands, which play a major role in hormone balance. CAH is a genetic condition caused by mutations (changes or variants) in the CYP21A2 gene. This gene provides instructions for the enzyme 21-hydroxylase, which helps produce hormones that regulate salt balance, blood pressure, and the way the body responds to stress.

In this article, we’ll explore what causes CAH, how it’s passed down through families, and when you should get genetic testing.

CAH and 21-Hydroxylase

Your body uses 21-hydroxylase to control your body’s hormone production. This enzyme is found mainly in the adrenal glands — the small glands that sit on top of your kidneys. Normally, the adrenal glands make the hormones aldosterone, cortisol, and androgen.

People with CAH don’t make enough 21-hydroxylase. When there isn’t enough of this enzyme, the substances used to make aldosterone and cortisol begin building up inside the adrenal glands. The body turns these substances into androgens (often called male sex hormones) instead. This is why CAH causes high androgen levels.

21-Hydroxylase Levels Affect Which Type of CAH You Have

Doctors typically divide CAH into two types: classic and nonclassic. The type you have depends on how high your androgen levels are. These levels are affected by how well the 21-hydroxylase enzyme works.

Classic CAH is the most severe form. It’s divided into two subtypes: salt-wasting CAH and simple-virilizing CAH. The salt-wasting form is the more serious of the two. In people with this condition, the 21-hydroxylase enzyme only works around 1 percent as well as it should. In simple-virilizing CAH, the enzyme has about 1 percent to 5 percent activity. This means it works better, but still not as well as it should.

Nonclassic CAH develops when you make enough 21-hydroxylase to have normal aldosterone and cortisol levels. However, you still have high androgen levels that lead to physical symptoms.

People with low 21-hydroxylase and too high androgen levels have abnormal sexual development. Per MedlinePlus, in females, CAH can cause:

• Excess body hair growth, especially on the face
• Irregular menstrual periods
• Infertility
• Male pattern baldness

In males, higher androgen levels can lead to small testes and early puberty with beard growth.

How Is CAH Inherited?

CAH is a genetic condition, meaning it’s passed down through family members. To better understand the chances of inheriting CAH, it helps to understand the basics of genetics.

Everyone receives one set of 23 chromosomes from each parent — humans have a total of 46 chromosomes. These structures contain thousands of genes encoded in DNA. Because you inherit one set of chromosomes from each parent, you typically get one copy of each gene.

CAH develops when people have variants in the CYP21A2 gene. It’s known as an autosomal recessive disorder. “Recessive” is a scientific way of saying you need two variant copies of a gene to develop a disease. This means that people with CAH receive two variant CYP21A2 genes — one from each of their parents.

Let’s say that two people have a child. They’re both carriers for CAH, meaning they have one healthy copy of CYP21A2 (A) and one variant copy (a). Carriers don’t experience any symptoms of CAH because they have another normal copy of the CYP21A2 gene to compensate (to make up for the one with the variant).

The two people pass one gene copy each onto the child, meaning there are three outcomes:

• AA — The child doesn’t have CAH and isn’t a carrier (25 percent chance).
• Aa — The child doesn’t have CAH but is a carrier (50 percent chance)
• aa — The child has CAH (25 percent chance)

Overall, you have a one-in-four chance of having a child with CAH if you and your partner are both carriers.

Certain Racial and Ethnic Groups Are More Likely to Develop CAH

Studies show that certain groups of people are at a higher risk of developing CAH. For example, white people in the United States are more likely to have this condition than African Americans. Researchers have found that 1 in every 15,500 babies is born with CAH. Rates are much lower in other places around the world — like China, where it affects every 1 in 28,000 people. CAH can still be seen in people from all over the world or with any ancestry.

Genetic Testing for CAH

If your doctor thinks you may have CAH, genetic testing will help confirm your diagnosis. Cares Foundation states that you may want to get testing done if you’re experiencing fertility problems or if you’re a female with high androgen levels. Genetic testing for CAH uses a blood or saliva test that’s sent to a lab to look for variants in your CYP21A2 gene. Further testing can find the exact CYP21A2 variant you have.

Family Planning With CAH

Genetic testing does more than confirm that you have CAH. You can also let your family know about your condition so they can get tested as well. Getting tested helps you and your family prepare for the future.

When you have CAH, that means you have two variant copies of the CYP21A2 gene. If you have siblings, there’s a chance they may also have CAH or be carriers. They may pass the variant gene onto their children. If their partner is also a carrier, they may have a child with CAH.

If you or a family member finds out they’re a carrier or have CAH, there are resources to help. Ask your doctor or endocrinologist (hormone specialist) about genetic counseling. Genetic counselors are professionals who work with people diagnosed with or who are carriers of genetic disorders. They can help you prepare for having a child with CAH and connect you with resources.

Prenatal Testing for CAH

If you’re pregnant and have a family history of CAH, your doctor or genetic counselor may recommend prenatal testing. It’s a good idea if you already have one child with CAH, as there’s a chance you could have another. You may also want to get prenatal testing if you or your partner has CAH, or if you know you’re both carriers.

There are two different prenatal tests to check for CAH. Both involve taking cell samples from the tissues or fluid around the growing fetus. The samples are sent to a lab for genetic testing to see if the fetus has CAH.

In amniocentesis, a needle is inserted through the abdomen and into the uterus. The doctor performing the procedure uses the needle to take a sample of amniotic fluid around the fetus. Another option is chorionic villus sampling, which takes a sample of the chorionic villi. This tissue later develops into the placenta — it provides oxygen and nutrients to the growing fetus. The doctor inserts a needle into the abdomen or cervix to get the sample.

Newborn Screening

If you don’t know that you or your partner are carriers for CAH, it can still be diagnosed early. Every state in the U.S. performs newborn screening for CAH. Keep in mind that this test can only look for classic CAH and not nonclassic CAH.

A health care provider will take a small blood sample from your baby’s heel shortly after they’re born. The sample is sent to a lab to measure your baby’s 17-hydroxyprogesterone (17-OHP) levels. If they have CAH with low levels of 21-hydroxylase and high cortisol, they’ll likely have higher 17-OHP levels as well.

Genetic testing can confirm a diagnosis, identify carriers, and help with family planning. Early diagnosis through newborn screening and prenatal tests is crucial for managing CAH effectively and reducing health risks. To learn more about CAH and how it’s inherited, talk to your doctor or a genetic counselor.

Find Your Team

On CAHteam, the social network for people with congenital adrenal hyperplasia and their loved ones, members come together to ask questions, give advice, and share their stories with others who understand life with CAH.

Are you or a loved one living with CAH? Do you have other questions about how it’s passed down through families? Share your experience in the comments below.