Hyper IgE syndrome 3 D82.4

Frey-Jakobs S et al. 2018

Hyper-IgE syndrome consists of a small group of rare, genetically heterogeneous, mostly autosomal recessive inherited immunodeficiency syndromes (multisystem disease) with the following clinical triad:

Recurrent skin infections mainly due to staphylococci (skin abscesses, with low inflammation/cold abscesses).

recurrent upper and lower respiratory tract infections (bronchitis, bronchopneumonia-J18.0)

excessive elevation of serum IgE and recurrent blood eosinophilia (D72.1).

In addition, depending on the genotype, there are a number of other clinical symptoms (skeletal abnormalities, including craniosynostosis and scoliosis, short stature, hip dislocation, craniosynostosis, bronchiectasis, finger contractures, elbow contractures, impacted teeth, high palate, atopic dermatitis; diarrhea, speech disorders).

Hyper-IgE syndrome 3 based on a pathogenic variant in ZNF341 (c.904C>T, NM_001282933.1) fulfills these criteria. This IgE variant was first detected in 2018 in a Muslim village population in Israel (Frey-Jakobs S et al. 2018). The ZNF341-HIES phenotype causes significant morbidity.

Because the oldest known patient in the studied collective is less than 30 years old, the life expectancy of these patients is still unknown (Frey-Jakobs S et al. 2018).

The described patients (n=8) of the "founder population" had a combination of high IgE levels, severe atopic dermatitis, bacterial skin infections with cold abscesses, recurrent bronchitis and pneumonia, oral thrush and mental retardation. These patients required regular preventive antibiotic treatment.

All eight patients were descendants of consanguineous couples (first cousins) from three families living in a Muslim village in northern Israel (Frey-Jakobs S et al. 2018).

1. Frey-Jakobs S et al (2018) ZNF341 Controls STAT3 Expression and Thereby Immunocompetence. Sci Immunol 3(24):1-11.
2. Grimbacher B et al (1999) Genetic linkage of hyper-IgE syndrome to chromosome 4. Am J Hum Genet 65:735-744.