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Hyper-IgE recurrent infection syndrome 3, autosomal recessive(HIES3)

MedGen UID:
1648483
Concept ID:
C4748969
Disease or Syndrome
Synonym: HYPER-IgE SYNDROME 3, AUTOSOMAL RECESSIVE, WITH RECURRENT INFECTIONS
 
Gene (location): ZNF341 (20q11.22)
 
Monarch Initiative: MONDO:0032654
OMIM®: 618282

Definition

Hyper-IgE syndrome-3 with recurrent infections (HIES3) is an autosomal recessive immunologic disorder characterized by childhood onset of atopic dermatitis, skin infections particularly with Staphylococcus aureus, recurrent sinopulmonary infections, and increased serum IgE and IgG. Patients are susceptible to bacterial and fungal infections, including chronic mucocutaneous candidiasis. Immunologic workup shows impaired differentiation of CD4+ T cells into T-helper 17 cells, decreased memory B cells, and often decreased NK cells (summary by Beziat et al., 2018). For a discussion of genetic heterogeneity of hyper-IgE syndrome, see HIES1 (147060). [from OMIM]

Clinical features

From HPO
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Pulmonic stenosis
MedGen UID:
408291
Concept ID:
C1956257
Disease or Syndrome
A narrowing of the right ventricular outflow tract that can occur at the pulmonary valve (valvular stenosis), below the pulmonary valve (infundibular stenosis), or above the pulmonary valve (supravalvar stenosis).
Intellectual disability, mild
MedGen UID:
10044
Concept ID:
C0026106
Mental or Behavioral Dysfunction
Mild intellectual disability is defined as an intelligence quotient (IQ) in the range of 50-69.
Micrognathia
MedGen UID:
44428
Concept ID:
C0025990
Congenital Abnormality
Developmental hypoplasia of the mandible.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
The capability that a joint (or a group of joints) has to move, passively and/or actively, beyond normal limits along physiological axes.
Spinal canal stenosis
MedGen UID:
396107
Concept ID:
C1861329
Anatomical Abnormality
An abnormal narrowing of the spinal canal.
Bronchiectasis
MedGen UID:
14234
Concept ID:
C0006267
Disease or Syndrome
Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways.
Recurrent sinusitis
MedGen UID:
107919
Concept ID:
C0581354
Disease or Syndrome
A recurrent form of sinusitis.
Recurrent pneumonia
MedGen UID:
195802
Concept ID:
C0694550
Disease or Syndrome
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Recurrent respiratory infections
MedGen UID:
812812
Concept ID:
C3806482
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
Chronic mucocutaneous candidiasis
MedGen UID:
2426
Concept ID:
C0006845
Disease or Syndrome
Recurrent or persistent superficial Candida infections of the skin, mucous membranes, and nails.
Atopic eczema
MedGen UID:
41502
Concept ID:
C0011615
Disease or Syndrome
Atopic dermatitis (ATOD), also known as eczema, is a common chronic pruritic inflammatory skin disease with a strong genetic component. Onset typically occurs during the first 2 years of life (review by Soderhall et al., 2007). Genetic Heterogeneity of Atopic Dermatitis Many inflammatory diseases, such as atopic eczema, are genetically complex, with multiple alleles at several loci thought to be involved in their pathogenesis. Several susceptibility loci for atopic dermatitis have been identified: ATOD1 on chromosome 3q21, ATOD2 (605803) on chromosome 1q21, ATOD3 (605804) on chromosome 20p, ATOD4 (605805) on chromosome 17q25.3, ATOD5 (603165) on chromosome 13q12-q14, ATOD6 (605845) on chromosome 5q31-q33, ATOD7 (613064) on chromosome 11q13.5, ATOD8 (613518) on chromosome 4q22.1, and ATOD9 (613519) on chromosome 3p24.
Eczematoid dermatitis
MedGen UID:
3968
Concept ID:
C0013595
Disease or Syndrome
Eczema is a form of dermatitis that is characterized by scaly, pruritic, erythematous lesions located on flexural surfaces.
Eosinophilia
MedGen UID:
41824
Concept ID:
C0014457
Disease or Syndrome
Increased count of eosinophils in the blood.
Osteomyelitis
MedGen UID:
10497
Concept ID:
C0029443
Disease or Syndrome
Osteomyelitis is an inflammatory process accompanied by bone destruction and caused by an infecting microorganism.
Cutaneous abscess
MedGen UID:
450991
Concept ID:
C0149777
Pathologic Function
A circumscribed area of pus or necrotic debris in the skin.
Decreased circulating IgA level
MedGen UID:
57934
Concept ID:
C0162538
Disease or Syndrome
Decreased levels of immunoglobulin A (IgA).
Increased circulating IgE level
MedGen UID:
116018
Concept ID:
C0236175
Finding
An abnormally increased overall level of immunoglobulin E in blood.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Methicillin-resistant staphylococcus aureus infectious disease
MedGen UID:
575565
Concept ID:
C0343401
Disease or Syndrome
Infection with staphylococcus aureus resistant to the antibiotic methicillin (MRSA). MRSA can infect any individual but is more common among hospitalized patients, and can also occur as an opportunistic infection.
Sterile abscess
MedGen UID:
639046
Concept ID:
C0541754
Acquired Abnormality
An abscess not caused by infection with pyogenic bacteria. Operationally, a sterile abscess is inferred if investigations of an abscess fail to reveal evidence of pathogenic organisms.
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
Recurrent skin infections
MedGen UID:
377848
Concept ID:
C1853193
Disease or Syndrome
Infections of the skin that happen multiple times.
Chronic oral candidiasis
MedGen UID:
870166
Concept ID:
C4024599
Disease or Syndrome
Chronic accumulation and overgrowth of the fungus Candida albicans on the mucous membranes of the mouth, generally manifested as associated with creamy white lesions on the tongue or inner cheeks, occasionally spreading to the gums, tonsils, palate or oropharynx.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Abnormality of the dentition
MedGen UID:
78084
Concept ID:
C0262444
Finding
Any abnormality of the teeth.
Wide nose
MedGen UID:
140869
Concept ID:
C0426421
Finding
Interalar distance more than two standard deviations above the mean for age, i.e., an apparently increased width of the nasal base and alae.
Alopecia
MedGen UID:
7982
Concept ID:
C0002170
Finding
A noncongenital process of hair loss, which may progress to partial or complete baldness.
Pruritus
MedGen UID:
19534
Concept ID:
C0033774
Sign or Symptom
Pruritus is an itch or a sensation that makes a person want to scratch. This term refers to an abnormally increased disposition to experience pruritus.
Dry skin
MedGen UID:
56250
Concept ID:
C0151908
Sign or Symptom
Skin characterized by the lack of natural or normal moisture.

Professional guidelines

PubMed

Aydin SE, Kilic SS, Aytekin C, Kumar A, Porras O, Kainulainen L, Kostyuchenko L, Genel F, Kütükcüler N, Karaca N, Gonzalez-Granado L, Abbott J, Al-Zahrani D, Rezaei N, Baz Z, Thiel J, Ehl S, Marodi L, Orange JS, Sawalle-Belohradsky J, Keles S, Holland SM, Sanal Ö, Ayvaz DC, Tezcan I, Al-Mousa H, Alsum Z, Hawwari A, Metin A, Matthes-Martin S, Hönig M, Schulz A, Picard C, Barlogis V, Gennery A, Ifversen M, van Montfrans J, Kuijpers T, Bredius R, Dückers G, Al-Herz W, Pai SY, Geha R, Notheis G, Schwarze CP, Tavil B, Azik F, Bienemann K, Grimbacher B, Heinz V, Gaspar HB, Aydin R, Hagl B, Gathmann B, Belohradsky BH, Ochs HD, Chatila T, Renner ED, Su H, Freeman AF, Engelhardt K, Albert MH; inborn errors working party of EBMT
J Clin Immunol 2015 Feb;35(2):189-98. Epub 2015 Jan 28 doi: 10.1007/s10875-014-0126-0. PMID: 25627830

Recent clinical studies

Etiology

Garib V, Ben-Ali M, Kundi M, Curin M, Yaakoubi R, Ben-Mustapha I, Mekki N, Froeschl R, Perkmann T, Valenta R, Barbouche MR
Allergy 2022 Jun;77(6):1761-1771. Epub 2021 Nov 2 doi: 10.1111/all.15143. PMID: 34653276Free PMC Article
Eken A, Cansever M, Okus FZ, Erdem S, Nain E, Azizoglu ZB, Haliloglu Y, Karakukcu M, Ozcan A, Devecioglu O, Aksu G, Arikan Ayyildiz Z, Topal E, Karakoc Aydiner E, Kiykim A, Metin A, Cipe F, Kaya A, Artac H, Reisli I, Guner SN, Uygun V, Karasu G, Dönmez Altuntas H, Canatan H, Oukka M, Ozen A, Chatila TA, Keles S, Baris S, Unal E, Patiroglu T
Allergy 2020 Apr;75(4):921-932. Epub 2019 Oct 31 doi: 10.1111/all.14081. PMID: 31596517Free 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
Abolhassani H, Chou J, Bainter W, Platt CD, Tavassoli M, Momen T, Tavakol M, Eslamian MH, Gharagozlou M, Movahedi M, Ghadami M, Hamidieh AA, Azizi G, Yazdani R, Afarideh M, Ghajar A, Havaei A, Chavoshzadeh Z, Mahdaviani SA, Cheraghi T, Behniafard N, Amin R, Aleyasin S, Faridhosseini R, Jabbari-Azad F, Nabavi M, Bemanian MH, Arshi S, Molatefi R, Sherkat R, Mansouri M, Mesdaghi M, Babaie D, Mohammadzadeh I, Ghaffari J, Shafiei A, Kalantari N, Ahanchian H, Khoshkhui M, Soheili H, Dabbaghzadeh A, Shirkani A, Nasiri Kalmarzi R, Mortazavi SH, Tafaroji J, Khalili A, Mohammadi J, Negahdari B, Joghataei MT, Al-Ramadi BK, Picard C, Parvaneh N, Rezaei N, Chatila TA, Massaad MJ, Keles S, Hammarström L, Geha RS, Aghamohammadi A
J Allergy Clin Immunol 2018 Apr;141(4):1450-1458. Epub 2017 Sep 12 doi: 10.1016/j.jaci.2017.06.049. PMID: 28916186
Yang L, Fliegauf M, Grimbacher B
Curr Opin Pediatr 2014 Dec;26(6):697-703. doi: 10.1097/MOP.0000000000000158. PMID: 25365149

Diagnosis

Garib V, Ben-Ali M, Kundi M, Curin M, Yaakoubi R, Ben-Mustapha I, Mekki N, Froeschl R, Perkmann T, Valenta R, Barbouche MR
Allergy 2022 Jun;77(6):1761-1771. Epub 2021 Nov 2 doi: 10.1111/all.15143. PMID: 34653276Free PMC Article
Bergerson JRE, Freeman AF
Immunol Allergy Clin North Am 2019 Feb;39(1):49-61. doi: 10.1016/j.iac.2018.08.007. PMID: 30466772
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
Ponsford MJ, Klocperk A, Pulvirenti F, Dalm VASH, Milota T, Cinetto F, Chovancova Z, Rial MJ, Sediva A, Litzman J, Agostini C, van Hagen M, Quinti I, Jolles S
Allergy 2018 Nov;73(11):2122-2136. Epub 2018 Oct 2 doi: 10.1111/all.13578. PMID: 30043993
Szczawinska-Poplonyk A, Kycler Z, Pietrucha B, Heropolitanska-Pliszka E, Breborowicz A, Gerreth K
Orphanet J Rare Dis 2011 Nov 15;6:76. doi: 10.1186/1750-1172-6-76. PMID: 22085750Free PMC Article

Prognosis

Kasap N, Kara A, Celik V, Bilgic Eltan S, Akay Haci I, Kose H, Aygun A, Akkelle E, Yakici N, Guner SN, Reisli I, Keles S, Cekic S, Kilic SS, Karaca NE, Gulez N, Genel F, Ozen A, Yucelten AD, Karakoc-Aydiner E, Schmitz-Abe K, Baris S
J Clin Immunol 2023 Nov;43(8):1882-1890. Epub 2023 Jul 29 doi: 10.1007/s10875-023-01554-z. PMID: 37507632
Ponsford MJ, Klocperk A, Pulvirenti F, Dalm VASH, Milota T, Cinetto F, Chovancova Z, Rial MJ, Sediva A, Litzman J, Agostini C, van Hagen M, Quinti I, Jolles S
Allergy 2018 Nov;73(11):2122-2136. Epub 2018 Oct 2 doi: 10.1111/all.13578. PMID: 30043993
Abolhassani H, Chou J, Bainter W, Platt CD, Tavassoli M, Momen T, Tavakol M, Eslamian MH, Gharagozlou M, Movahedi M, Ghadami M, Hamidieh AA, Azizi G, Yazdani R, Afarideh M, Ghajar A, Havaei A, Chavoshzadeh Z, Mahdaviani SA, Cheraghi T, Behniafard N, Amin R, Aleyasin S, Faridhosseini R, Jabbari-Azad F, Nabavi M, Bemanian MH, Arshi S, Molatefi R, Sherkat R, Mansouri M, Mesdaghi M, Babaie D, Mohammadzadeh I, Ghaffari J, Shafiei A, Kalantari N, Ahanchian H, Khoshkhui M, Soheili H, Dabbaghzadeh A, Shirkani A, Nasiri Kalmarzi R, Mortazavi SH, Tafaroji J, Khalili A, Mohammadi J, Negahdari B, Joghataei MT, Al-Ramadi BK, Picard C, Parvaneh N, Rezaei N, Chatila TA, Massaad MJ, Keles S, Hammarström L, Geha RS, Aghamohammadi A
J Allergy Clin Immunol 2018 Apr;141(4):1450-1458. Epub 2017 Sep 12 doi: 10.1016/j.jaci.2017.06.049. PMID: 28916186
Engelhardt KR, Gertz ME, Keles S, Schäffer AA, Sigmund EC, Glocker C, Saghafi S, Pourpak Z, Ceja R, Sassi A, Graham LE, Massaad MJ, Mellouli F, Ben-Mustapha I, Khemiri M, Kilic SS, Etzioni A, Freeman AF, Thiel J, Schulze I, Al-Herz W, Metin A, Sanal Ö, Tezcan I, Yeganeh M, Niehues T, Dueckers G, Weinspach S, Patiroglu T, Unal E, Dasouki M, Yilmaz M, Genel F, Aytekin C, Kutukculer N, Somer A, Kilic M, Reisli I, Camcioglu Y, Gennery AR, Cant AJ, Jones A, Gaspar BH, Arkwright PD, Pietrogrande MC, Baz Z, Al-Tamemi S, Lougaris V, Lefranc G, Megarbane A, Boutros J, Galal N, Bejaoui M, Barbouche MR, Geha RS, Chatila TA, Grimbacher B
J Allergy Clin Immunol 2015 Aug;136(2):402-12. Epub 2015 Feb 25 doi: 10.1016/j.jaci.2014.12.1945. PMID: 25724123Free PMC Article
Aydin SE, Kilic SS, Aytekin C, Kumar A, Porras O, Kainulainen L, Kostyuchenko L, Genel F, Kütükcüler N, Karaca N, Gonzalez-Granado L, Abbott J, Al-Zahrani D, Rezaei N, Baz Z, Thiel J, Ehl S, Marodi L, Orange JS, Sawalle-Belohradsky J, Keles S, Holland SM, Sanal Ö, Ayvaz DC, Tezcan I, Al-Mousa H, Alsum Z, Hawwari A, Metin A, Matthes-Martin S, Hönig M, Schulz A, Picard C, Barlogis V, Gennery A, Ifversen M, van Montfrans J, Kuijpers T, Bredius R, Dückers G, Al-Herz W, Pai SY, Geha R, Notheis G, Schwarze CP, Tavil B, Azik F, Bienemann K, Grimbacher B, Heinz V, Gaspar HB, Aydin R, Hagl B, Gathmann B, Belohradsky BH, Ochs HD, Chatila T, Renner ED, Su H, Freeman AF, Engelhardt K, Albert MH; inborn errors working party of EBMT
J Clin Immunol 2015 Feb;35(2):189-98. Epub 2015 Jan 28 doi: 10.1007/s10875-014-0126-0. PMID: 25627830

Clinical prediction guides

Kasap N, Kara A, Celik V, Bilgic Eltan S, Akay Haci I, Kose H, Aygun A, Akkelle E, Yakici N, Guner SN, Reisli I, Keles S, Cekic S, Kilic SS, Karaca NE, Gulez N, Genel F, Ozen A, Yucelten AD, Karakoc-Aydiner E, Schmitz-Abe K, Baris S
J Clin Immunol 2023 Nov;43(8):1882-1890. Epub 2023 Jul 29 doi: 10.1007/s10875-023-01554-z. PMID: 37507632
Béziat V, Fieschi C, Momenilandi M, Migaud M, Belaid B, Djidjik R, Puel A
Curr Opin Immunol 2023 Jun;82:102326. Epub 2023 Apr 18 doi: 10.1016/j.coi.2023.102326. PMID: 37080116Free PMC Article
Szczawinska-Poplonyk A, Kycler Z, Pietrucha B, Heropolitanska-Pliszka E, Breborowicz A, Gerreth K
Orphanet J Rare Dis 2011 Nov 15;6:76. doi: 10.1186/1750-1172-6-76. PMID: 22085750Free PMC Article
Minegishi Y
Curr Opin Immunol 2009 Oct;21(5):487-92. Epub 2009 Aug 28 doi: 10.1016/j.coi.2009.07.013. PMID: 19717292
Minegishi Y, Karasuyama H
Int Immunol 2009 Feb;21(2):105-12. Epub 2008 Dec 15 doi: 10.1093/intimm/dxn134. PMID: 19088064

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