Hyperimmunoglobulin E syndrome type 2 D82.4

Genetic heterogeneity of hyper IgE recurrent infection syndrome.

• HIES1 (147060) caused by an autosomal dominant mutation in the STAT3 gene (102582
• HIES2 (243700) caused by a mutation in the DOCK8 gene (611432),
• HIES3 (618282) caused by a mutation in the ZNF341 gene (618269),
• HIES4A (619752) and HIES4B (618523), both caused by a mutation in the IL6ST gene (600694),
• HIES5 (618944), caused by a mutation in the IL6R gene (147880).

AR-HIES is inherited in an autosomal recessive manner and is caused by mutations in the DOCK8 gene.Hyper-IgE recurrent infection syndrome 2 is related to immunodeficiency syndrome 35.

Autosomal dominant hyper-IgE syndrome 1 (HIES1; 147060) is a primary immunodeficiency disease characterized by recurrent Staphylococcus aureus skin abscesses, elevated serum IgE, and abnormalities of connective tissue, skeleton, and dentition (Buckley et al., 1972; Grimbacher et al.1999).

Autosomal recessive hyper-IgE syndrome 2 (HIES2) also has hyper-IgE, eosinophilia, and recurrent staphylococcal infections, but differs from autosomal dominant HIES1 in the absence of connective tissue and skeletal involvement (Renner et al., 2004). See also TYK2 deficiency (611521), a clinically distinct disease entity that has characteristic features of both autosomal recessive HIES2 and Mendelian susceptibility to mycobacterial disease (MSMD; 209950) (Minegishi et al., 2006).

1. Asano T et al (2021) Human STAT3 variants underlie autosomal dominant hyper-IgE syndrome by negative dominance. J Exp Med 218: e20202592.
2. Buckley RH et al (1972) Extreme hyperimmunoglobulin E and susceptibility to infection. Pediatrics 49: 59-70.
3. Grimbacher B et al (1999) Hyper-IgE syndrome with recurrent infections--an autosomal dominant multisystem disorder. New Eng J Med 340: 692-702.
4. Milner JD et al (2008) Impaired TH17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 452: 773-776.
5. Hoger PH et al (1985) Craniosynostosis in hyper-IgE-syndrome. Europ. J. Pediat. 144: 414-417
6. Minegishi Y et al (2006) Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity. Immunity 25: 745-755.
7. Zhang Q et al (2009) Combined immunodeficiency associated with DOCK8 mutations. New Eng J Med 361: 2046-2055.