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Autosomal dominant hyper-IgE syndrome
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Reviewed October 2015
What is autosomal dominant hyper-IgE syndrome?
Autosomal dominant hyper-IgE syndrome (AD-HIES), also known as Job syndrome, is a condition that affects several body systems, particularly the immune system. Recurrent infections are common in people with this condition. Affected individuals tend to have frequent bouts of pneumonia, which are caused by certain kinds of bacteria that infect the lungs and cause inflammation. These infections often result in the formation of air-filled cysts (pneumatoceles) in the lungs. Recurrent skin infections and an inflammatory skin disorder called eczema are also very common in AD-HIES. These skin problems cause rashes, blisters, accumulations of pus (abscesses), open sores, and scaling.
AD-HIES is characterized by abnormally high levels of an immune system protein called immunoglobulin E (IgE) in the blood. IgE normally triggers an immune response against foreign invaders in the body, particularly parasitic worms, and plays a role in allergies. It is unclear why people with AD-HIES have such high levels of IgE.
AD-HIES also affects other parts of the body, including the bones and teeth. Many people with AD-HIES have skeletal abnormalities such as an unusually large range of joint movement (hyperextensibility), an abnormal curvature of the spine (scoliosis), reduced bone density (osteopenia), and a tendency for bones to fracture easily. Dental abnormalities are also common in this condition. The primary (baby) teeth do not fall out at the usual time during childhood but are retained as the adult teeth grow in. Other signs and symptoms of AD-HIES can include abnormalities of the arteries that supply blood to the heart muscle (coronary arteries), distinctive facial features, and structural abnormalities of the brain, which do not affect a person's intelligence.
How common is autosomal dominant hyper-IgE syndrome?
This condition is rare, affecting fewer than 1 per million people.
What genes are related to autosomal dominant hyper-IgE syndrome?
Mutations in the STAT3 gene cause most cases of AD-HIES. This gene provides instructions for making a protein that plays an important role in several body systems. To carry out its roles, the STAT3 protein attaches to DNA and helps control the activity of particular genes. In the immune system, the STAT3 protein regulates genes that are involved in the maturation of immune system cells, especially T cells. These cells help control the body's response to foreign invaders such as bacteria and fungi.
Changes in the STAT3 gene alter the structure and function of the STAT3 protein, impairing its ability to control the activity of other genes. A shortage of functional STAT3 blocks the maturation of T cells (specifically a subset known as Th17 cells) and other immune cells. The resulting immune system abnormalities make people with AD-HIES highly susceptible to infections, particularly bacterial and fungal infections of the lungs and skin. The STAT3 protein is also involved in the formation of cells that build and break down bone tissue, which could help explain why STAT3 gene mutations lead to the skeletal and dental abnormalities characteristic of this condition. It is unclear how STAT3 gene mutations lead to increased IgE levels.
When AD-HIES is not caused by STAT3 gene mutations, the genetic cause of the condition is unknown.
Read more about the STAT3 gene.
How do people inherit autosomal dominant hyper-IgE syndrome?
AD-HIES has an autosomal dominant pattern of inheritance, which means one copy of an altered gene in each cell is sufficient to cause the disorder. In about half of all cases caused by STAT3 gene mutations, an affected person inherits the genetic change from an affected parent. Other cases result from new mutations in this gene. These cases occur in people with no history of the disorder in their family.
Where can I find information about diagnosis or management of autosomal dominant hyper-IgE syndrome?
These resources address the diagnosis or management of autosomal dominant hyper-IgE syndrome and may include treatment providers.
General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.
To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.
Where can I find additional information about autosomal dominant hyper-IgE syndrome?
You may find the following resources about autosomal dominant hyper-IgE syndrome helpful. These materials are written for the general public.
You may also be interested in these resources, which are designed for healthcare professionals and researchers.
What other names do people use for autosomal dominant hyper-IgE syndrome?
What if I still have specific questions about autosomal dominant hyper-IgE syndrome?
Where can I find general information about genetic conditions?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding autosomal dominant hyper-IgE syndrome?
arteries ; autosomal ; autosomal dominant ; bacteria ; bone density ; candidiasis ; cell ; coronary ; cysts ; deficiency ; DNA ; eczema ; gene ; immune response ; immune system ; immunodeficiency ; immunoglobulin ; infection ; inflammation ; inheritance ; joint ; osteopenia ; pattern of inheritance ; pneumonia ; protein ; scoliosis ; syndrome ; tissue
You may find definitions for these and many other terms in the Genetics Home Reference Glossary.
See also Understanding Medical Terminology.
References (8 links)
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? in the Handbook.