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]
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) |
| Cleft palate | 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) |
| Aneurysm | Occasional (present in 5%-29% of cases) |
| Cellulitis | 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 | - |
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]
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]
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.
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.
Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.
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.
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.
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
- 49KB)
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.
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