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Hyper-IgE recurrent infection syndrome 1, autosomal dominant

MedGen UID:
445391
Concept ID:
C2936739
Disease or Syndrome
Synonyms: AD hyperimmunoglobulin E syndrome; Autosomal Dominant Hyper IgE Syndrome; HIES autosomal dominant; Hyper Ig E syndrome, autosomal dominant; Hyper-IgE recurrent infection syndrome 1; HYPER-IgE SYNDROME 1, AUTOSOMAL DOMINANT, WITH RECURRENT INFECTIONS; Hyperimmunoglobulin E recurrent infection syndrome, autosomal dominant; JOB SYNDROME; Job's Syndrome
Modes of inheritance:
 
STAT3 (17q21.2)
 
Monarch Initiative: MONDO:0007818
OMIM®: 147060
Orphanet: ORPHA2314

Disease characteristics

Excerpted from the GeneReview: STAT3 Hyper IgE Syndrome
STAT3 hyper IgE syndrome (STAT3-HIES) is a primary immune deficiency syndrome characterized by elevated serum IgE, eczema, and recurrent skin and respiratory tract infections, together with several nonimmune features. This disorder typically manifests in the newborn period with a rash (often diagnosed as eosinophilic pustulosis) that subsequently evolves into an eczematoid dermatitis. Recurrent staphylococcal skin boils and bacterial pneumonias usually manifest in the first years of life. Pneumatoceles and bronchiectasis often result from aberrant healing of pneumonias. Mucocutaneous candidiasis is common. Nonimmune features may include retained primary teeth, scoliosis, bone fractures following minimal trauma, joint hyperextensibility, and characteristic facial appearance, which typically emerges in adolescence. Vascular abnormalities have been described and include middle-sized artery tortuosity and aneurysms, with infrequent clinical sequelae of myocardial infarction and subarachnoid hemorrhage. Gastrointestinal (GI) manifestations include gastroesophageal reflux disease, esophageal dysmotility, and spontaneous intestinal perforations (some of which are associated with diverticuli). Fungal infections of the GI tract (typically histoplasmosis, Cryptococcus, and Coccidioides) also occur infrequently. Survival is typically into adulthood, with most individuals now living into or past the sixth decade. Most deaths are associated with gram-negative (Pseudomonas) or filamentous fungal pneumonias resulting in hemoptysis. Lymphomas occur at an increased frequency. [from GeneReviews]
Authors:
Amy P Hsu  |  Joie Davis  |  Jennifer M Puck, et. al.   view full author information

Additional descriptions

From OMIM
Hyper-IgE syndrome-1 with recurrent infections (HIES1) is an autosomal dominant immunologic disorder characterized by chronic eczema (atopy), recurrent Staphylococcal infections, increased serum IgE, and eosinophilia. Other more variable immunologic abnormalities include defective granulocyte chemotaxis, abnormalities in T-lymphocyte subgroups, impaired antibody production, and decreased production of or response to certain cytokines. Importantly, the same immune system defects are not found in all patients. Some patients may have a distinctive coarse facial appearance, abnormal dentition, hyperextensibility of the joints, and bone fractures (Buckley et al., 1972; Grimbacher et al., 1999). Genetic Heterogeneity of Hyper-IgE Syndrome See also HIES2 (243700), caused by mutation in the DOCK8 gene (611432); HIES3 (618282), caused by mutation in the ZNF341 gene (618269); HIES4A (619752) and HIES4B (618523), both caused by mutation in the IL6ST gene (600694); HIES5 (618944), caused by mutation in the IL6R gene (147880); and HIES6 (620532), caused by mutation in the STAT6 gene (601512).  http://www.omim.org/entry/147060
From MedlinePlus Genetics
Autosomal dominant hyper-IgE syndrome (AD-HIES), formerly known as Job syndrome, is a condition that affects several body systems, particularly the immune system. Recurrent infections are common in people with this condition. Affected individuals tend to have frequent bouts of pneumonia, which are caused by certain kinds of bacteria that infect the lungs and cause inflammation. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). However, excessive inflammation can damage body tissues. Recurring pneumonia often results in the formation of air-filled cysts (pneumatoceles) in the lungs. Frequent skin infections and an inflammatory skin disorder called eczema are also very common in AD-HIES. These skin problems cause rashes, blisters, accumulations of pus (abscesses), open sores, and scaling.

For unknown reasons, people with AD-HIES have abnormally high levels of an immune system protein called immunoglobulin E (IgE) in the blood. IgE normally triggers an immune response against foreign invaders in the body, particularly parasitic worms, and is involved in allergies. However, IgE is not needed for these roles in people with AD-HIES, and it is unclear why affected individuals have such high levels of the protein without having allergies.

AD-HIES also affects other parts of the body, including the bones and teeth. Many people with AD-HIES 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. A common dental abnormality in this condition is that 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 abnormalities of the arteries that supply blood to the heart muscle (coronary arteries), distinctive facial features, and structural abnormalities of the brain, which do not affect a person's intelligence.  https://medlineplus.gov/genetics/condition/autosomal-dominant-hyper-ige-syndrome

Clinical features

From HPO

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHyper-IgE recurrent infection syndrome 1, autosomal dominant

Professional guidelines

PubMed

Sabbagh Q, Cohen JD, Mortreux J, Raymond L, Geromel V, Boursier G, Jeziorski E, Le Moing V, Bessis D, Geneviève D
Dermatitis 2023 Nov-Dec;34(6):561-563. Epub 2023 Jan 19 doi: 10.1089/derm.2022.0057. PMID: 36917542
James AE, West L, Schloss K, Nataraj P, Urban A, Hirsch A, Krausz M, Kumar S, Raasch J, Risma K, Church JA, Grimbacher B, Bergerson JRE, Chong H, Freeman AF
J Allergy Clin Immunol Pract 2022 May;10(5):1367-1370.e1. Epub 2022 Jan 24 doi: 10.1016/j.jaip.2022.01.011. PMID: 35085810
Flinn AM, Cant A, Leahy TR, Butler KM, Gennery AR
J Clin Immunol 2016 Feb;36(2):107-9. Epub 2016 Jan 7 doi: 10.1007/s10875-015-0231-8. PMID: 26743515

Recent clinical studies

Etiology

Quesada-Puga C, Izquierdo-Espin FJ, Membrive-Jiménez MJ, Aguayo-Estremera R, Cañadas-De La Fuente GA, Romero-Béjar JL, Gómez-Urquiza JL
Intensive Crit Care Nurs 2024 Jun;82:103660. Epub 2024 Feb 22 doi: 10.1016/j.iccn.2024.103660. PMID: 38394983
Gharehzadehshirazi A, Amini A, Rezaei N
Clin Immunol 2022 Apr;237:108988. Epub 2022 Mar 26 doi: 10.1016/j.clim.2022.108988. PMID: 35351598
Tsilifis C, Freeman AF, Gennery AR
J Clin Immunol 2021 Jul;41(5):864-880. Epub 2021 May 1 doi: 10.1007/s10875-021-01051-1. PMID: 33932191Free PMC Article
Bravata DM, Watts SA, Keefer AL, Madhusudhan DK, Taylor KT, Clark DM, Nelson RS, Cokley KO, Hagg HK
J Gen Intern Med 2020 Apr;35(4):1252-1275. Epub 2019 Dec 17 doi: 10.1007/s11606-019-05364-1. PMID: 31848865Free PMC Article
Al-Shaikhly T, Ochs HD
Immunol Cell Biol 2019 Apr;97(4):368-379. Epub 2018 Nov 19 doi: 10.1111/imcb.12209. PMID: 30264496

Diagnosis

Gracci S, Novelli T, D'Elios S, Bernardini R, Peroni D
Curr Pediatr Rev 2024;20(3):253-264. doi: 10.2174/1573396320666230912103124. PMID: 37702167
Gharehzadehshirazi A, Amini A, Rezaei N
Clin Immunol 2022 Apr;237:108988. Epub 2022 Mar 26 doi: 10.1016/j.clim.2022.108988. PMID: 35351598
Bravata DM, Watts SA, Keefer AL, Madhusudhan DK, Taylor KT, Clark DM, Nelson RS, Cokley KO, Hagg HK
J Gen Intern Med 2020 Apr;35(4):1252-1275. Epub 2019 Dec 17 doi: 10.1007/s11606-019-05364-1. PMID: 31848865Free PMC Article
Al-Shaikhly T, Ochs HD
Immunol Cell Biol 2019 Apr;97(4):368-379. Epub 2018 Nov 19 doi: 10.1111/imcb.12209. PMID: 30264496
Bridgeman PJ, Bridgeman MB, Barone J
Am J Health Syst Pharm 2018 Feb 1;75(3):147-152. Epub 2017 Nov 28 doi: 10.2146/ajhp170460. PMID: 29183877

Therapy

Rashid J, Kumar SS, Job KM, Liu X, Fike CD, Sherwin CMT
Paediatr Drugs 2020 Jun;22(3):279-293. doi: 10.1007/s40272-020-00384-5. PMID: 32140997Free PMC Article
Filippi M, Bar-Or A, Piehl F, Preziosa P, Solari A, Vukusic S, Rocca MA
Nat Rev Dis Primers 2018 Nov 8;4(1):43. doi: 10.1038/s41572-018-0041-4. PMID: 30410033
Weatherall MW
Pract Neurol 2007 Aug;7(4):212-21. doi: 10.1136/jnnp.2007.124511. PMID: 17636136
Field T, Hernandez-Reif M, Diego M, Schanberg S, Kuhn C
Int J Neurosci 2005 Oct;115(10):1397-413. doi: 10.1080/00207450590956459. PMID: 16162447
Andronikou S, Eimany A, Robinson PJ, Kemp A
S Afr Med J 2004 Mar;94(3):166-7. PMID: 15098273

Prognosis

Gracci S, Novelli T, D'Elios S, Bernardini R, Peroni D
Curr Pediatr Rev 2024;20(3):253-264. doi: 10.2174/1573396320666230912103124. PMID: 37702167
Bravata DM, Watts SA, Keefer AL, Madhusudhan DK, Taylor KT, Clark DM, Nelson RS, Cokley KO, Hagg HK
J Gen Intern Med 2020 Apr;35(4):1252-1275. Epub 2019 Dec 17 doi: 10.1007/s11606-019-05364-1. PMID: 31848865Free PMC Article
Filippi M, Bar-Or A, Piehl F, Preziosa P, Solari A, Vukusic S, Rocca MA
Nat Rev Dis Primers 2018 Nov 8;4(1):43. doi: 10.1038/s41572-018-0041-4. PMID: 30410033
Salvagioni DAJ, Melanda FN, Mesas AE, González AD, Gabani FL, Andrade SM
PLoS One 2017;12(10):e0185781. Epub 2017 Oct 4 doi: 10.1371/journal.pone.0185781. PMID: 28977041Free PMC Article
Nouri A, Tetreault L, Singh A, Karadimas SK, Fehlings MG
Spine (Phila Pa 1976) 2015 Jun 15;40(12):E675-93. doi: 10.1097/BRS.0000000000000913. PMID: 25839387

Clinical prediction guides

Grenier PA, Brun AL, Longchampt E, Lipski M, Mellot F, Catherinot E
Eur Radiol 2024 Jun;34(6):4142-4154. Epub 2023 Nov 8 doi: 10.1007/s00330-023-10334-7. PMID: 37935849Free PMC Article
Gracci S, Novelli T, D'Elios S, Bernardini R, Peroni D
Curr Pediatr Rev 2024;20(3):253-264. doi: 10.2174/1573396320666230912103124. PMID: 37702167
Bravata DM, Watts SA, Keefer AL, Madhusudhan DK, Taylor KT, Clark DM, Nelson RS, Cokley KO, Hagg HK
J Gen Intern Med 2020 Apr;35(4):1252-1275. Epub 2019 Dec 17 doi: 10.1007/s11606-019-05364-1. PMID: 31848865Free PMC Article
Nouri A, Tetreault L, Singh A, Karadimas SK, Fehlings MG
Spine (Phila Pa 1976) 2015 Jun 15;40(12):E675-93. doi: 10.1097/BRS.0000000000000913. PMID: 25839387
Romani M, Ashkar K
Libyan J Med 2014;9(1):23556. Epub 2014 Feb 17 doi: 10.3402/ljm.v9.23556. PMID: 24560380Free PMC Article

Recent systematic reviews

Quesada-Puga C, Izquierdo-Espin FJ, Membrive-Jiménez MJ, Aguayo-Estremera R, Cañadas-De La Fuente GA, Romero-Béjar JL, Gómez-Urquiza JL
Intensive Crit Care Nurs 2024 Jun;82:103660. Epub 2024 Feb 22 doi: 10.1016/j.iccn.2024.103660. PMID: 38394983
Bravata DM, Watts SA, Keefer AL, Madhusudhan DK, Taylor KT, Clark DM, Nelson RS, Cokley KO, Hagg HK
J Gen Intern Med 2020 Apr;35(4):1252-1275. Epub 2019 Dec 17 doi: 10.1007/s11606-019-05364-1. PMID: 31848865Free PMC Article
Rotenstein LS, Torre M, Ramos MA, Rosales RC, Guille C, Sen S, Mata DA
JAMA 2018 Sep 18;320(11):1131-1150. doi: 10.1001/jama.2018.12777. PMID: 30326495Free PMC Article
Salvagioni DAJ, Melanda FN, Mesas AE, González AD, Gabani FL, Andrade SM
PLoS One 2017;12(10):e0185781. Epub 2017 Oct 4 doi: 10.1371/journal.pone.0185781. PMID: 28977041Free PMC Article
Copanitsanou P, Fotos N, Brokalaki H
Br J Nurs 2017 Feb 9;26(3):172-176. doi: 10.12968/bjon.2017.26.3.172. PMID: 28185485

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