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

This disease is grouped under:

Hyper IgE syndrome

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

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms	Other Names	Learn More: HPO ID
80%-99% of people have these symptoms
Atelectasis	Partial or complete collapse of part or entire lung	0100750
Eczema		0000964
Generalized abnormality of skin	Generalised abnormality of skin	0011354
Increased IgE level		0003212
Pruritus	Itching Itchy skin Skin itching [ more ]	0000989
Recurrent respiratory infections	Frequent respiratory infections Multiple respiratory infections respiratory infections, recurrent Susceptibility to respiratory infections [ more ]	0002205
Skin rash		0000988
Skin ulcer	Open skin sore	0200042
30%-79% of people have these symptoms
Abnormality of the hair	Hair abnormality	0001595
Chronic otitis media	Chronic infections of the middle ear	0000389
Cleft palate		0000175
Cough	Coughing	0012735
Deeply set eye	Deep set eye Deep-set eyes Sunken eye [ more ]	0000490
Delayed eruption of teeth	Delayed eruption Delayed teeth eruption Delayed tooth eruption Eruption, delayed Late eruption of teeth Late tooth eruption [ more ]	0000684
Dystrophic fingernails	Poor fingernail formation	0008391
Eosinophilia	High blood eosinophil count	0001880
Gingivitis	Inflamed gums Red and swollen gums [ more ]	0000230
Joint hyperflexibility	Joints move beyond expected range of motion	0005692
Osteopenia		0000938
Papule		0200034
Paronychia		0001818
Prominent forehead	Pronounced forehead Protruding forehead [ more ]	0011220
Recurrent fractures	Increased fracture rate Increased fractures Multiple fractures Multiple spontaneous fractures Varying degree of multiple fractures [ more ]	0002757
Scoliosis	Abnormal curving of the spine	0002650
Wide nasal bridge	Broad nasal bridge Broad nasal root Broadened nasal bridge Increased breadth of bridge of nose Increased breadth of nasal bridge Increased width of bridge of nose Increased width of nasal bridge Nasal bridge broad Wide bridge of nose Widened nasal bridge [ more ]	0000431
5%-29% of people have these symptoms
Cellulitis	Bacterial infection of skin Skin infection [ more ]	0100658
Craniosynostosis		0001363
Dilatation	Wider than typical opening or gap	0002617
Fever		0001945
Lymphoma	Cancer of lymphatic system	0002665
Osteomyelitis	Bone infection	0002754
Skin vesicle	Blister	0200037
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance		0000006
Coarse facial features	Coarse facial appearance	0000280
Eczematoid dermatitis		0000976
Erythema		0010783
Frontal bossing		0002007
High palate	Elevated palate Increased palatal height [ more ]	0000218
Hypertelorism	Wide-set eyes Widely spaced eyes [ more ]	0000316
Infantile onset	Onset in first year of life Onset in infancy [ more ]	0003593
Joint hypermobility	Double-Jointed Flexible joints Increased mobility of joints [ more ]	0001382
Persistence of primary teeth	Delayed loss of baby teeth Failure to lose baby teeth Retained baby teeth [ more ]	0006335
Recurrent fungal infections		0002841
Recurrent sinopulmonary infections		0005425
Recurrent Staphylococcus aureus infections		0002726
Wide nose	Broad nose Increased breadth of nose Increased nasal breadth Increased nasal width Increased width of nose [ more ]	0000445

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Do you have more information about symptoms of this disease? We want to hear from you.

Last updated: 12/1/2018

Do you have updated information on this disease? We want to hear from you.

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.

Find a Specialist Find a Specialist

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare 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 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.

Related Diseases Related Diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
The differential diagnosis should include cystic fibrosis and chronic granulomatous disease (see these terms), as well as severe atopic dermatitis and HIV-infection. A clinically distinct autosomal recessive hyper-IgE syndrome has also been described (AR-HIES; see this term). Visit the Orphanet disease page for more information.

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 related to 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.

Patient Registry

United States Immunodeficiency Network (USIDNET)
110 West Road, Suite 300
Towson, MD 21204-4803
Toll-free: 800-296-4433 (se habla español)
Telephone: 443-632-2558
E-mail: contact@usidnet.org
Website: https://www.usidnet.org

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: 1-800-296-4433
Fax: +1-410-321-9165
E-mail: https://www.primaryimmune.org/services/ask-idf/
Website: https://www.primaryimmune.org/
Primary Immune Deficiency UK (PID UK)
PO Box 6970
Basingstoke, RG24 4XL United Kingdom
Toll-free: 0800 987 8986
E-mail: hello@piduk.org
Website: http://www.piduk.org/

Do you know of an organization? We want to hear from you.

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

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.
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.

GARD Answers GARD Answers

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

Have a question? Contact a GARD Information Specialist.

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.

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