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  • The following term was not found in MedGen: com2.

Hyper-IgE syndrome 6, autosomal dominant, with recurrent infections(HIES6)

MedGen UID:
1851769
Concept ID:
C5848786
Disease or Syndrome
Synonym: HIES6
 
Gene (location): STAT6 (12q13.3)
 
Monarch Initiative: MONDO:0957807
OMIM®: 620532

Definition

Hyper-IgE syndrome-6 with recurrent infections (HIES6) is an autosomal dominant immunologic disorder characterized by early-childhood onset of severe refractory atopic dermatitis, IgE-mediated food and drug allergies, asthma, and eosinophilic esophagitis. Laboratory studies show increased serum IgE levels and eosinophilia. Affected individuals are susceptible to life-threatening anaphylaxis. Additional features may include allergic rhinitis, recurrent secondary infections (bacterial, viral, fungal), and short stature. Rare patients show intracerebral vascular abnormalities, including the Circle of Willis, increased risk of ruptured aneurysm, and B-cell lymphoma. The disorder results from immune dysregulation with inappropriate activation of inflammatory signaling pathways associated with a Th2 phenotype. Treatment with an IL4 (147780)/IL13 (147683) inhibitor (dupilumab) or JAK inhibitor results in clinical improvement. Sharma et al. (2023) classified this disease as a 'primary atopic disorder' (PAD). For a discussion of genetic heterogeneity of hyper-IgE syndrome, see HIES1 (147060). [from OMIM]

Clinical features

From HPO
B-cell lymphoma
MedGen UID:
86953
Concept ID:
C0079731
Neoplastic Process
A type of lymphoma that originates in B-cells.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Eosinophilic gastroenteritis
MedGen UID:
220382
Concept ID:
C1262481
Disease or Syndrome
Eosinophilic infiltration of one or more gastrointestinal organs. Gastrointestinal eosinophilia is a broad term for abnormal eosinophil accumulation in the GI tract, involving many different disease identities. These diseases include primary eosinophil associated gastrointestinal diseases, gastrointestinal eosinophilia in HES and all gastrointestinal eosinophilic states associated with known causes. Each of these diseases has its unique features but there is no absolute boundary between them.
Gastroesophageal reflux
MedGen UID:
1368658
Concept ID:
C4317146
Finding
A condition in which the stomach contents leak backwards from the stomach into the esophagus through the lower esophageal sphincter.
Eosinophilic infiltration of the esophagus
MedGen UID:
1637185
Concept ID:
C4703646
Finding
Infiltration of numerous eosinophils (usually greater than 15 per high power field) into the squamous epithelium of the esophagus, and layering of eosinophils on the surface layer of the esophagus.
Osteoporosis
MedGen UID:
14535
Concept ID:
C0029456
Disease or Syndrome
Osteoporosis is a systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. According to the WHO criteria, osteoporosis is defined as a BMD that lies 2.5 standard deviations or more below the average value for young healthy adults (a T-score below -2.5 SD).
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.
Asthma
MedGen UID:
2109
Concept ID:
C0004096
Disease or Syndrome
Asthma is characterized by increased responsiveness of the tracheobronchial tree to multiple stimuli, leading to narrowing of the air passages with resultant dyspnea, cough, and wheezing.
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.
Eosinophilia
MedGen UID:
41824
Concept ID:
C0014457
Disease or Syndrome
Increased count of eosinophils in the blood.
Increased circulating IgE concentration
MedGen UID:
116018
Concept ID:
C0236175
Finding
An abnormally increased overall level of immunoglobulin E in blood.
Recurrent viral infections
MedGen UID:
332357
Concept ID:
C1837066
Finding
Increased susceptibility to viral infections, as manifested by recurrent episodes of viral infection.
Recurrent skin infections
MedGen UID:
377848
Concept ID:
C1853193
Disease or Syndrome
Infections of the skin that happen multiple times.
Anaphylactic shock
MedGen UID:
1373755
Concept ID:
C4316895
Pathologic Function
An acute hypersensitivity reaction due to exposure to a previously encountered antigen.
Food allergy
MedGen UID:
1635115
Concept ID:
C4554344
Disease or Syndrome
Primary food allergies primarily occur as a result (most likely) of gastrointestinal sensitization to predominantly stable food allergens (glycoproteins). A secondary food allergy develops after primary sensitization to airborne allergens (e. g., pollen allergens) with subsequent reactions (due to cross-reactivity) to structurally related often labile allergens in (plant) foods.

Recent clinical studies

Etiology

Nihal A, Comstock JR, Holland KE, Singh AM, Seroogy CM, Arkin LM
Pediatr Dermatol 2022 Nov;39(6):940-942. Epub 2022 Jun 22 doi: 10.1111/pde.15072. PMID: 35734823Free PMC Article
Duréault A, Tcherakian C, Poiree S, Catherinot E, Danion F, Jouvion G, Bougnoux ME, Mahlaoui N, Givel C, Castelle M, Picard C, Chansdesris MO, Lortholary O, Lanternier F; French Mycoses Study Group
J Allergy Clin Immunol Pract 2019 Jul-Aug;7(6):1986-1995.e3. Epub 2019 Mar 13 doi: 10.1016/j.jaip.2019.02.041. PMID: 30878710
Chandesris MO, Melki I, Natividad A, Puel A, Fieschi C, Yun L, Thumerelle C, Oksenhendler E, Boutboul D, Thomas C, Hoarau C, Lebranchu Y, Stephan JL, Cazorla C, Aladjidi N, Micheau M, Tron F, Baruchel A, Barlogis V, Palenzuela G, Mathey C, Dominique S, Body G, Munzer M, Fouyssac F, Jaussaud R, Bader-Meunier B, Mahlaoui N, Blanche S, Debré M, Le Bourgeois M, Gandemer V, Lambert N, Grandin V, Ndaga S, Jacques C, Harre C, Forveille M, Alyanakian MA, Durandy A, Bodemer C, Suarez F, Hermine O, Lortholary O, Casanova JL, Fischer A, Picard C
Medicine (Baltimore) 2012 Jul;91(4):e1-e19. doi: 10.1097/MD.0b013e31825f95b9. PMID: 22751495Free PMC Article
Al Khatib S, Keles S, Garcia-Lloret M, Karakoc-Aydiner E, Reisli I, Artac H, Camcioglu Y, Cokugras H, Somer A, Kutukculer N, Yilmaz M, Ikinciogullari A, Yegin O, Yüksek M, Genel F, Kucukosmanoglu E, Baki A, Bahceciler NN, Rambhatla A, Nickerson DW, McGhee S, Barlan IB, Chatila T
J Allergy Clin Immunol 2009 Aug;124(2):342-8, 348.e1-5. Epub 2009 Jul 3 doi: 10.1016/j.jaci.2009.05.004. PMID: 19577286Free PMC Article
Grimbacher B, Holland SM, Gallin JI, Greenberg F, Hill SC, Malech HL, Miller JA, O'Connell AC, Puck JM
N Engl J Med 1999 Mar 4;340(9):692-702. doi: 10.1056/NEJM199903043400904. PMID: 10053178

Diagnosis

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
Verras GG, Mulita F, Chlorogiannis DD, Liolis E, Perdikaris I, Perdikaris P, Bouchagie K, Akrida I
Med Arch 2022 Dec;76(6):476-479. doi: 10.5455/medarh.2022.76.476-479. PMID: 36937610Free PMC Article
Nihal A, Comstock JR, Holland KE, Singh AM, Seroogy CM, Arkin LM
Pediatr Dermatol 2022 Nov;39(6):940-942. Epub 2022 Jun 22 doi: 10.1111/pde.15072. PMID: 35734823Free PMC Article
Duréault A, Tcherakian C, Poiree S, Catherinot E, Danion F, Jouvion G, Bougnoux ME, Mahlaoui N, Givel C, Castelle M, Picard C, Chansdesris MO, Lortholary O, Lanternier F; French Mycoses Study Group
J Allergy Clin Immunol Pract 2019 Jul-Aug;7(6):1986-1995.e3. Epub 2019 Mar 13 doi: 10.1016/j.jaip.2019.02.041. PMID: 30878710
Deng Y, Li T, Xie X, Xia D, Ding L, Xiang H, Ma JJ, Li W
Medicine (Baltimore) 2019 Feb;98(6):e14003. doi: 10.1097/MD.0000000000014003. PMID: 30732127Free PMC Article

Therapy

Verras GG, Mulita F, Chlorogiannis DD, Liolis E, Perdikaris I, Perdikaris P, Bouchagie K, Akrida I
Med Arch 2022 Dec;76(6):476-479. doi: 10.5455/medarh.2022.76.476-479. PMID: 36937610Free PMC Article
Duréault A, Tcherakian C, Poiree S, Catherinot E, Danion F, Jouvion G, Bougnoux ME, Mahlaoui N, Givel C, Castelle M, Picard C, Chansdesris MO, Lortholary O, Lanternier F; French Mycoses Study Group
J Allergy Clin Immunol Pract 2019 Jul-Aug;7(6):1986-1995.e3. Epub 2019 Mar 13 doi: 10.1016/j.jaip.2019.02.041. PMID: 30878710
Deng Y, Li T, Xie X, Xia D, Ding L, Xiang H, Ma JJ, Li W
Medicine (Baltimore) 2019 Feb;98(6):e14003. doi: 10.1097/MD.0000000000014003. PMID: 30732127Free PMC Article
Sowerwine KJ, Shaw PA, Gu W, Ling JC, Collins MT, Darnell DN, Anderson VL, Davis J, Hsu A, Welch P, Puck JM, Holland SM, Freeman AF
J Clin Immunol 2014 Feb;34(2):260-4. Epub 2014 Jan 9 doi: 10.1007/s10875-013-9982-2. PMID: 24402620Free PMC Article

Prognosis

Verras GG, Mulita F, Chlorogiannis DD, Liolis E, Perdikaris I, Perdikaris P, Bouchagie K, Akrida I
Med Arch 2022 Dec;76(6):476-479. doi: 10.5455/medarh.2022.76.476-479. PMID: 36937610Free PMC Article
Chandesris MO, Melki I, Natividad A, Puel A, Fieschi C, Yun L, Thumerelle C, Oksenhendler E, Boutboul D, Thomas C, Hoarau C, Lebranchu Y, Stephan JL, Cazorla C, Aladjidi N, Micheau M, Tron F, Baruchel A, Barlogis V, Palenzuela G, Mathey C, Dominique S, Body G, Munzer M, Fouyssac F, Jaussaud R, Bader-Meunier B, Mahlaoui N, Blanche S, Debré M, Le Bourgeois M, Gandemer V, Lambert N, Grandin V, Ndaga S, Jacques C, Harre C, Forveille M, Alyanakian MA, Durandy A, Bodemer C, Suarez F, Hermine O, Lortholary O, Casanova JL, Fischer A, Picard C
Medicine (Baltimore) 2012 Jul;91(4):e1-e19. doi: 10.1097/MD.0b013e31825f95b9. PMID: 22751495Free PMC Article
Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N, Freeman AF, Demidowich A, Davis J, Turner ML, Anderson VL, Darnell DN, Welch PA, Kuhns DB, Frucht DM, Malech HL, Gallin JI, Kobayashi SD, Whitney AR, Voyich JM, Musser JM, Woellner C, Schäffer AA, Puck JM, Grimbacher B
N Engl J Med 2007 Oct 18;357(16):1608-19. Epub 2007 Sep 19 doi: 10.1056/NEJMoa073687. PMID: 17881745
van der meer JW, Weemaes CM, van Krieken JH, Blomjous CE, van Die CE, Netea MG, Bredie SJ
J Intern Med 2006 Jun;259(6):615-8. doi: 10.1111/j.1365-2796.2006.01653.x. PMID: 16704563

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
Wu J, Chen J, Tian ZQ, Zhang H, Gong RL, Chen TX, Hong L
J Clin Immunol 2017 Feb;37(2):166-179. Epub 2017 Feb 14 doi: 10.1007/s10875-017-0369-7. PMID: 28197791
Chandesris MO, Melki I, Natividad A, Puel A, Fieschi C, Yun L, Thumerelle C, Oksenhendler E, Boutboul D, Thomas C, Hoarau C, Lebranchu Y, Stephan JL, Cazorla C, Aladjidi N, Micheau M, Tron F, Baruchel A, Barlogis V, Palenzuela G, Mathey C, Dominique S, Body G, Munzer M, Fouyssac F, Jaussaud R, Bader-Meunier B, Mahlaoui N, Blanche S, Debré M, Le Bourgeois M, Gandemer V, Lambert N, Grandin V, Ndaga S, Jacques C, Harre C, Forveille M, Alyanakian MA, Durandy A, Bodemer C, Suarez F, Hermine O, Lortholary O, Casanova JL, Fischer A, Picard C
Medicine (Baltimore) 2012 Jul;91(4):e1-e19. doi: 10.1097/MD.0b013e31825f95b9. PMID: 22751495Free PMC Article
Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N, Freeman AF, Demidowich A, Davis J, Turner ML, Anderson VL, Darnell DN, Welch PA, Kuhns DB, Frucht DM, Malech HL, Gallin JI, Kobayashi SD, Whitney AR, Voyich JM, Musser JM, Woellner C, Schäffer AA, Puck JM, Grimbacher B
N Engl J Med 2007 Oct 18;357(16):1608-19. Epub 2007 Sep 19 doi: 10.1056/NEJMoa073687. PMID: 17881745

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