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Congenital adrenal hyperplasia (CAH) is one of the most common inherited hormone conditions worldwide. It affects the adrenal glands — two small organs on the kidneys that make hormones that control stress, blood pressure, salt balance, and sexual development. Someone who has CAH makes too little of some of these hormones but too much of others.
CAH is a lifelong condition, but early diagnosis and treatment are critical for preventing serious complications. In this article, we’ll explain what causes CAH, how it’s passed down in families, and when testing is recommended.
Most cases of CAH are caused by mutations (changes) in a gene called CYP21A2. This gene provides instructions for making 21-hydroxylase, an enzyme that’s critical for producing enough cortisol and aldosterone. When CYP21A2 is altered, 21-hydroxylase deficiency and hormone imbalances result.
Scientists have identified many CYP21A2 variants. Some variants result in very little enzyme activity, causing the most severe forms of CAH (known as classic CAH). Others allow partial activity, leading to milder forms (nonclassic CAH).
Other rare forms of CAH can be caused by changes in genes that affect different enzymes. For example, changes in the CYP11B1 gene lead to 11-hydroxylase deficiency.
When there isn’t enough of these enzymes, the substances used to make cortisol and aldosterone build up inside the adrenal glands and are instead turned into androgens (sometimes called male sex hormones). This is why CAH causes high androgen levels.
Doctors typically divide CAH into two main types — classic and nonclassic.
Classic CAH, the most severe type, usually shows up in babies and young children. This form is divided into two subtypes:
Nonclassic CAH develops when your body can make enough 21-hydroxylase to have normal cortisol and aldosterone levels. However, you can still have high androgen levels. If nonclassic CAH symptoms occur, they typically first appear later in childhood, as well as adolescence or adulthood.
Females with classic forms of CAH may have atypical genitalia at birth, according to the National Institute of Child Health and Human Development. As they get older, they may develop extra facial or body hair, acne, or irregular menstrual periods. Males may have rapid childhood growth and early puberty, leading to short stature in adulthood.
Read more about different types of CAH.
CAH is a genetic condition — it’s passed down in families through autosomal recessive inheritance. This means a child must inherit two nonworking copies of a gene (one from each parent) to develop the condition.
Every person has 23 pairs of chromosomes, carrying thousands of genes made of DNA. For most genes, you receive one copy from each parent. A person with two disease-causing variants of CYP21A2 will have CAH.
People with just one variant and one healthy gene copy are called carriers of CAH. Carriers don’t have symptoms because the working gene makes enough enzyme. However, carriers can pass the variant gene on to their children. If both parents are carriers, the chances of their child having CAH are as follows:
Knowing your carrier status can be important for family planning. That’s why doctors and genetic counselors often recommend genetic testing and counseling for relatives of people with CAH.
CAH occurs worldwide, but reported rates vary depending on whether newborn screening or genetic testing is used. Classic CAH affects about 1 in 18,000 births in the United States. In Europe, incidence rates typically range from about 1 in 12,000 to 1 in 18,000. Studies from Asia report slightly lower rates, such as 1 in 20,000 to 21,000 in regions of Japan.
Nonclassic CAH, the milder form, is more common but often underdiagnosed (because there may not be any symptoms). Genetic studies suggest it may affect about 1 in 100 people in the U.S. People of certain ancestral backgrounds, such as Ashkenazi Jews, Hispanics, and Slavic groups, have higher reported rates.
In every U.S. state, newborns are screened for classic CAH shortly after birth. This screening test measures 17-hydroxyprogesterone (17-OHP), a hormone that builds up when 21-hydroxylase enzyme isn’t working properly. If the results suggest classic CAH, doctors will order additional tests — including measurements of cortisol and other adrenal hormones — to confirm the diagnosis.
A doctor may also order genetic testing, which uses a blood or saliva test that’s sent to a lab to look for variants in the CYP21A2 gene. Further testing can pinpoint the exact CYP21A2 variant. Cares Foundation notes that you may want to get testing done if you’re experiencing fertility problems or if you’re a woman with high androgen levels.
Genetic testing does more than confirm a CAH diagnosis. You can also let your family know about your condition so they can get tested too. The results can help you and your family prepare for the future.
If you have CAH, you have two variant copies of the CYP21A2 gene. Your siblings also may have CAH or be carriers and may pass the variant gene on to their children. If your sibling’s partner is also a carrier, the couple may have a child with CAH.
If you or a family member finds out they are a carrier or have CAH, there are resources to help. Ask your doctor or endocrinologist (hormone specialist) about genetic counseling. Genetic counselors work with people who have or are carriers of genetic disorders. These healthcare professionals can help you prepare for having a child with CAH and connect you with resources.
If you’re pregnant and have a family history of CAH, your doctor or genetic counselor may recommend prenatal testing. This is especially important if you already have a child with CAH, as there’s a chance future children could also inherit the condition. Testing may also be considered if you or your partner has CAH or if you know you’re both carriers.
Two prenatal tests can check for CAH. Both tests involve taking cell samples from the tissue 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. 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 sample is taken either through the cervix using a thin tube or through the abdomen using a needle.
As mentioned above, all U.S. states include CAH — specifically classic 21-hydroxylase deficiency — in their newborn screening panels. These programs are designed to detect classic CAH because it can be life-threatening. Nonclassic CAH usually isn’t detectable until childhood, adolescence, or adulthood.
Newborn screening is performed within the first few days after birth, and some states require babies to be tested twice. A healthcare provider takes a small amount of blood from your baby’s heel, and this sample is sent to a lab to measure 17-OHP levels. Elevated 17-OHP levels suggest possible CAH and prompt further testing. Babies with CAH often also have low levels of cortisol and aldosterone.
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 with your doctor or a genetic counselor.
On CAHteam, people share their experiences with congenital adrenal hyperplasia, get advice, and find support from others who understand.
Do you know if CAH runs in your family? Have you had genetic testing? Let others know in the comments below.
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