IllnessHyper-IgE syndrome, differential diagnosis

NGS +

Autosomal dominant hyper IgE syndrome (STAT-HIES; Job syndrome) caused by STAT3 mutations affects multiple body systems, especially the immune system with immunodeficiency. Recurrent infections such as pneumonia are common that form pneumatoceles. Skin infections and eczema are equally common. For unknown reasons, HIES patients have abnormally high blood levels of IgE. STAT-HIES also affects teeth and bones, the latter with hyperextensibility, scoliosis, osteopenia and a tendency to fracture. Deciduous teeth are retained. Other symptoms may include abnormalities of the coronary arteries, prominent facial features, and structural abnormalities of the brain, but these do not affect intelligence. In addition to STAT3, the most important genes to consider in the differential diagnosis are DOCK8, IL6R, IL6ST and TYK2, each of which follows an autosomal recessive inheritance pattern. A comprehensive differential diagnosis for high IgE levels includes additional genes: CARD11/-14, FLG, PGM3, RAG1/-2, SPINK5, WAS. The DNA diagnostic yield is not known. A negative molecular genetic result does not exclude the clinical diagnosis.

References: https://www.ncbi.nlm.nih.gov/books/NBK25507/

https://www.ncbi.nlm.nih.gov/books/NBK525947/

• Alias: Job syndrome
• Alias: STAT3 Loss-of-function hyper-IgE syndrome
• Alias: STAT3 deficiency
• Alias: STAT3-HIES
• Alias: STAT3-deficient hyper-IgE syndrome
• Allelic: A/B T-cell lymphopenia + G/D T-cell expans., severe cytomegalov. infect., autoimmun. (RAG1)
• Allelic: Autoimmune disease, multisystem, infantile-onset, 1 (STAT3)
• Allelic: B-cell expansion with NFKB and T-cell anergy (CARD11)
• Allelic: Ichthyosis vulgaris (FLG)
• Allelic: Immunodeficiency 11A (CARD11)
• Allelic: Interleukin 6, serum level of, QTL (IL6R)
• Allelic: Interleukin-6 receptor, soluble, serum level of, QTL (IL6R)
• Allelic: Neutropenia, severe congenital, XL (WAS)
• Allelic: Omenn syndrome (RAG1, RAG2)
• Allelic: Severe combined immunodeficiency, B cell-negative (RAG1, RAg2)
• Allelic: Thrombocytopenia, XL (WAS)
• Allelic: Thrombocytopenia, XL, intermittent (WAS)
• Combined cellular + humoral immune defects with granulomas (RAG1, RAG2)
• Dermatitis, atopic, susceptibility to, 2 (FLG)
• Hyper-IgE recurrent infection syndrome (STAT3)
• Hyper-IgE recurrent infection syndrome 2, AR (DOCK8)
• Hyper-IgE recurrent infection syndrome 3, AR (ZNF341)
• Hyper-IgE recurrent infection syndrome 4, AR (IL6ST)
• Hyper-IgE recurrent infection syndrome 5, AR (IL6R)
• Immunodeficiency 11B with atopic dermatitis (CARD11)
• Immunodeficiency 23 (PGM3)
• Immunodeficiency 35 (TYK2)
• Immunodysregulation, polyendocrinopathy + enteropathy, XL (FOXP3)
• Netherton syndrome (SPINK5)
• Omenn syndrome (DCLRE1C)
• Pityriasis rubra pilaris (CARD14)
• Psoriasis 2 (CARD14)
• Severe combined immunodeficiency, Athabascan type (DCLRE1C)
• Wiskott-Aldrich syndrome (WAS)