Hyper-IgE syndrome (HIES) [28 genes]

There are two main forms of hyper-IgE syndrome (HIES) based on the altered gene and mode of inheritance: autosomal dominant (AD-HIES or Job syndrome), mainly caused by mutations in the STAT3 gene, which is involved in the maturation of T cells, specifically Th17 cells; and the more severe autosomal recessive form (AR-HIES) , which is generally explained by alterations in the DOCK8 gene, implicated in the stimulation of B cells and in the maintenance of the structure and integrity of T cells and NK cells. However, alterations in other genes explain the less common forms of the disease.

• AD-HIES: 1/10,000 – 100,000 individuals
• AR-HIES: 1/100,000 – 1,000,000 individuals

• Diagnosis and genetic counseling
• Skin hydration
• Antifungals
• Antibiotic prophylaxis
• Ig replacement (IVIG)
• Hematopoietic stem cell transplantation (HSCT)

Identifying a genetic defect responsible for the disease would allow a precise molecular diagnosis to be issued and make it possible to provide genetic counseling to the patient and their family members. In some cases, detecting a genetic variant can help explore specific treatment options.

Hyper-IgE syndrome is an inherited immunodeficiency that appears during childhood and is characterized by the early onset of recurrent abscesses (boils), sinus and lung infections, and a severe rash. Immunoglobulin E (IgE) concentrations are very high (> 2000 IU/ml).

• Respiratory and skin infections
• Elevated IgE levels
• Eczema
• Eosinophilia
• Asthma, Allergy, Autoimmunity, Immunodeficiency (AR-HIES)
• Joint, dental and bone problems (AD-HIES)
• Onset: neonatal, infancy