Autosomal dominant hyper IgE syndrome

Title

Other Names:

AD-HIES; Hyper Ig E syndrome, autosomal dominant; HIES autosomal dominant; AD-HIES; Hyper Ig E syndrome, autosomal dominant; HIES autosomal dominant; Hyperimmunoglobulin E recurrent infection syndrome, autosomal dominant; AD hyperimmunoglobulin E syndrome; Job syndrome autosomal dominant See More

Categories:

Congenital and Genetic Diseases; Immune System Diseases; Skin Diseases

Summary Summary

Autosomal dominant hyper IgE syndrome (AD-HIES), formerly known as Job syndrome, affects several body systems including the immune system. AD-HIES is characterized by abnormally high levels of an immune system protein called immunoglobulin E (IgE) in the blood. Signs and symptoms may include recurrent infections (e.g., pneumonia, skin infections), eczema, and occasionally bone and tooth abnormalities. The eczema and skin infections may cause rashes, blisters, collections of pus (abscesses), open sores, and scaling of the skin. Some cases of AD-HIES are caused by mutations in the STAT3 gene. In other cases, the cause is unknown.^[1]

Last updated: 7/14/2015

Symptoms Symptoms

Recurrent infections are common in people with autosomal dominant hyper IgE syndrome (AD-HIES). Affected individuals tend to have frequent bouts of pneumonia, which are caused by certain kinds of bacteria that infect the lungs and cause inflammation. Recurrent skin infections and an inflammatory skin disorder called eczema are also very common in AD-HIES). These skin problems cause rashes, blisters, collections of pus (abscesses), open sores, and scaling.^[1]

This condition also affects other parts of the body, including the bones and teeth. Many people with this condition 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 AD-HIES. 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 distinctive facial features and structural abnormalities of the brain, which typically do not affect a person's intelligence.^[1]

Last updated: 12/3/2015

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Atelectasis	Very frequent (present in 80%-99% of cases)
Eczema	Very frequent (present in 80%-99% of cases)
Generalized abnormality of skin	Very frequent (present in 80%-99% of cases)
Increased IgE level	Very frequent (present in 80%-99% of cases)
Pruritus	Very frequent (present in 80%-99% of cases)
Recurrent respiratory infections	Very frequent (present in 80%-99% of cases)
Skin rash	Very frequent (present in 80%-99% of cases)
Skin ulcer	Very frequent (present in 80%-99% of cases)
Abnormality of the hair	Frequent (present in 30%-79% of cases)
Chronic otitis media	Frequent (present in 30%-79% of cases)
Cough	Frequent (present in 30%-79% of cases)
Deeply set eye	Frequent (present in 30%-79% of cases)
Delayed eruption of teeth	Frequent (present in 30%-79% of cases)
Dystrophic fingernails	Frequent (present in 30%-79% of cases)
Eosinophilia	Frequent (present in 30%-79% of cases)
Gingivitis	Frequent (present in 30%-79% of cases)
Joint hyperflexibility	Frequent (present in 30%-79% of cases)
Osteopenia	Frequent (present in 30%-79% of cases)
Papule	Frequent (present in 30%-79% of cases)
Paronychia	Frequent (present in 30%-79% of cases)
Prominent forehead	Frequent (present in 30%-79% of cases)
Recurrent fractures	Frequent (present in 30%-79% of cases)
Scoliosis	Frequent (present in 30%-79% of cases)
Wide nasal bridge	Frequent (present in 30%-79% of cases)
Cellulitis	Occasional (present in 5%-29% of cases)
Dilatation	Occasional (present in 5%-29% of cases)
Fever	Occasional (present in 5%-29% of cases)
Lymphoma	Occasional (present in 5%-29% of cases)
Osteomyelitis	Occasional (present in 5%-29% of cases)
Skin vesicle	Occasional (present in 5%-29% of cases)
Autosomal dominant inheritance	-
Coarse facial features	-
Eczematoid dermatitis	-
Frontal bossing	-
High palate	-
Hypertelorism	-
Infantile onset	-
Joint hypermobility	-
Persistence of primary teeth	-
Recurrent fungal infections	-
Recurrent sinopulmonary infections	-
Recurrent Staphylococcus aureus infections	-
Wide nose	-

Last updated: 8/1/2017

Cause Cause

Most cases of AD-HIES are caused by mutations in the STAT3 gene . This gene provides instructions for making a protein that plays an important role in several body systems. The STAT3 protein is involved in controlling the activity of particular genes, including genes involved in the immune system, especially the T cells.

Changes in the STAT3 gene alter the structure and function of the STAT3 protein, impairing its ability to control the activity of other genes. The defective protein disrupts cellular functions such as immune system regulation. The resulting immune system abnormalities make people with AD-HIES highly susceptible to infections. The STAT3 protein is also involved in the formation of cells that build and break down bone tissue, which could explain why STAT3 gene mutations lead to the skeletal and dental abnormalities characteristic of AD-HIES. It remains unclear how STAT3 gene mutations lead to increased IgE levels.

When AD-HIES syndrome is not caused by STAT3 gene mutations, the genetic cause of is unknown.^[1]

Last updated: 6/8/2016

Inheritance Inheritance

Autosomal dominant hyper IgE syndrome (AD-HIES) has an autosomal dominant pattern of inheritance. This means that one copy of an altered gene in each cell is sufficient to cause the disorder. In about half of all cases, an affected person inherits a STAT3 mutation 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.^[1]

A small percentage (<5%) of individuals who have the clinical symptoms associated with AD-HIES do not have an identifiable mutation in the STAT3 gene. This suggests that there are additional unidentified mutations.^[2]

Last updated: 12/3/2015

Diagnosis Diagnosis

The diagnosis of autosomal dominant hyper IgE syndrome (AD-HIES) is most often made based on a combination of clinical and laboratory findings. Diagnostic guidelines have been developed that include both immunologic /infectious manifestations and skeletal/connective tissue abnormalities. Molecular genetic testing of the STAT3 gene confirms the diagnosis.^[2]

GeneReviews provides more detailed information about the diagnosis of AD-HIES.

Last updated: 12/3/2015

Testing Resources

The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

Treatment Treatment

The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

Management Guidelines

GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied Autosomal dominant hyper IgE syndrome. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Organizations Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Immune Deficiencies Foundation Australia
PO Box 969
Penrith NSW 2751
Australia
Telephone: 800-100-198
E-mail: info@idfa.org.au
Website: http://www.idfa.org.au/
Immune Deficiency Foundation
110 West Road, Suite 300
Towson, MD 21204
Toll-free: 800-296-4433
Fax: 410-321-9165
E-mail: idf@primaryimmune.org
Website: http://www.primaryimmune.org/
National Primary Immunodeficiency Resource Center
747 Third Avenue
New York, NY 10017
Toll-free: 800-533-3844
Telephone: 212-819-0200
Fax: 212-764-4180
E-mail: info@jmfworld.org
Website: http://www.info4pi.org
United States Immunodeficiency Network (USIDNET)
Towson, MD 21204-4803
Toll-free: 800-296-4433 (se habla español)
Fax: 410-321-9165
E-mail: info@usidnet.org
Website: http://www.usidnet.org

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Learn More Learn More

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

DermNet NZ is an online resource about skin diseases developed by the New Zealand Dermatological Society Incorporated. DermNet NZ provides information about this condition.
Genetics Home Reference (GHR) contains information on Autosomal dominant hyper IgE syndrome. This website is maintained by the National Library of Medicine.
MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine.
Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
PubMed is a searchable database of medical literature and lists journal articles that discuss Autosomal dominant hyper IgE syndrome. Click on the link to view a sample search on this topic.

News & Events News & Events

News

IRDiRC Goals 2017-2027: New Rare Disease Research Goals for the Next Decade
August 10, 2017

NCATS Co-Sponsored Conferences

The Jak/Stat Pathway: 20 Years from Discovery to Drugs Thursday, September 22, 2011 - Saturday, September 24, 2011
Location: NIH Natcher Center, Bethesda, MD
Description: As a scientific conference, the primary goal is the dissemination of recent data and developments in the field to intersted researchers in the field. The conference includes a scientific program and reception, which will help to foster collaboration and networking. Participants should achieve a better understanding of the state of the art research in this exciting and clinically relevant field.

Contact: Megan Laycock,(301) 594-7527Megan.laycock@nih.gov

Co-funding Institute(s): National Institute of Arthritis and Musculoskeletal and Skin Diseases, Office of Rare Diseases Research
- Agenda ( - 49KB)

Related Diseases Related Diseases

The following diseases are related to Autosomal dominant hyper IgE syndrome. If you have a question about any of these diseases, you can contact GARD.

Hyper IgE syndrome

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References References

Autosomal dominant hyper-IgE syndrome. Genetics Home Reference (GHR). October 2015; http://ghr.nlm.nih.gov/condition/autosomal-dominant-hyper-ige-syndrome.
Hsu AP, Davis J, Puck JM, Holland SM, Freeman AF. Autosomal Dominant Hyper IgE Syndrome. GeneReviews. June 2012; http://www.ncbi.nlm.nih.gov/books/NBK25507/. Accessed 12/3/2015.

Do you know of a review article? Send us your suggestions.