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Hyperimmunoglobulin E syndrome(HIES1)

MedGen UID:
1648470
Concept ID:
C4721531
Disease or Syndrome
Synonyms: AD hyperimmunoglobulin E syndrome; Autosomal Dominant Hyper IgE Syndrome; HIES autosomal dominant; HIES1; Hyper Ig E syndrome, autosomal dominant; HYPER-IgE RECURRENT INFECTION SYNDROME 1, AUTOSOMAL DOMINANT; Hyperimmunoglobulin E recurrent infection syndrome, autosomal dominant; Job syndrome; Job's Syndrome
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
 
Gene (location): STAT3 (17q21.2)
OMIM®: 147060

Disease characteristics

Excerpted from the GeneReview: Autosomal Dominant Hyper IgE Syndrome
Autosomal dominant hyper IgE syndrome (AD-HIES) is a primary immune deficiency characterized by the classic triad of recurrent skin boils, cyst-forming pneumonias, and extreme elevations of serum IgE. It is now recognized that other common manifestations include eczema, mucocutaneous candidiasis, and several connective tissue and skeletal abnormalities. A rash in the newborn period subsequently evolves into an eczematoid dermatitis. Recurrent staphylococcal skin boils and bacterial pneumonias usually manifest in the first years of life. Pneumatocoeles and bronchiectasis often result from aberrant healing of pneumonias. Mucocutaneous candidiasis is common. A characteristic facial appearance typically emerges in adolescence. Skeletal abnormalities include osteopenia, minimal trauma fractures, and scoliosis. Vascular abnormalities 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 rarely colonic perforations, some of which are associated with diverticuli. Fungal infection of the GI tract (typically histoplasmosis, Cryptococcus, and Coccidioides) also occur infrequently. Survival is typically into adulthood, but life span is often shortened. 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 recurrent infection syndrome is a primary immunodeficiency disorder characterized by chronic eczema, recurrent Staphylococcal infections, increased serum IgE, and eosinophilia. Patients 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 Recurrent Infection Syndrome See also HIES2 (243700), caused by mutation in the DOCK8 gene (611432), HIES3 (618282), caused by mutation in the ZNF341 gene (618269), and HIES4 (618523), caused by mutation in the IL6ST gene (600694).  http://www.omim.org/entry/147060
From GHR
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://ghr.nlm.nih.gov/condition/autosomal-dominant-hyper-ige-syndrome

Clinical features

From HPO
Erythema
MedGen UID:
11999
Concept ID:
C0041834
Disease or Syndrome
Red discoloration of the skin caused by infectious agents, inflammation, drug hypersensitivity, or underlying disease.
Chiari malformation type I
MedGen UID:
196689
Concept ID:
C0750929
Congenital Abnormality
Chiari malformation type I (CM1) is the protrusion of the cerebellar tonsils through the foramen magnum, defined radiologically as tonsillar descent of 5 mm or more. CM1 is associated with syringomyelia (see 186700) in up to 80% of cases. Although many individuals with CM1 are asymptomatic, the malformation can cause headaches, ocular disturbances, otoneurologic disturbances, lower cranial nerve signs, cerebellar ataxia, or spasticity. Onset of symptoms is usually in the third decade of life (Speer et al., 2003). Since many cases of CM1 are asymptomatic, prevalence estimates may not be accurate. However, a retrospective investigation of brain MRIs reported the prevalence of CM1 to be 1 in 1,280 individuals (Meadows et al., 2000).
Eosinophilia
MedGen UID:
41824
Concept ID:
C0014457
Disease or Syndrome
Abnormal increase of EOSINOPHILS in the blood, tissues or organs.
Recurrent pneumonia
MedGen UID:
195802
Concept ID:
C0694550
Finding
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Recurrent sinopulmonary infections
MedGen UID:
339549
Concept ID:
C1846546
Finding
An increased susceptibility to infections involving both the paranasal sinuses and the lungs, as manifested by a history of recurrent sinopulmonary infections.
Chronic mucocutaneous candidiasis
MedGen UID:
2426
Concept ID:
C0006845
Disease or Syndrome
A clinical syndrome characterized by development, usually in infancy or childhood, of a chronic, often widespread candidiasis of skin, nails, and mucous membranes. It may be secondary to one of the immunodeficiency syndromes, inherited as an autosomal recessive trait, or associated with defects in cell-mediated immunity, endocrine disorders, dental stomatitis, or malignancy.
Eosinophilia
MedGen UID:
41824
Concept ID:
C0014457
Disease or Syndrome
Abnormal increase of EOSINOPHILS in the blood, tissues or organs.
Skin rash
MedGen UID:
8732
Concept ID:
C0015230
Finding
A widespread, acute rash.
Ige, elevated level of
MedGen UID:
116018
Concept ID:
C0236175
Finding
An abnormally increased overall level of immunoglobulin E in blood.
Recurrent pneumonia
MedGen UID:
195802
Concept ID:
C0694550
Finding
An increased susceptibility to pneumonia as manifested by a history of recurrent episodes of pneumonia.
Recurrent fungal infections
MedGen UID:
336166
Concept ID:
C1844384
Finding
Increased susceptibility to fungal infections, as manifested by multiple episodes of fungal infection.
Recurrent sinopulmonary infections
MedGen UID:
339549
Concept ID:
C1846546
Finding
An increased susceptibility to infections involving both the paranasal sinuses and the lungs, as manifested by a history of recurrent sinopulmonary infections.
Recurrent Staphylococcus aureus infections
MedGen UID:
392925
Concept ID:
C2673462
Finding
Increased susceptibility to Staphylococcus aureus infections, as manifested by recurrent episodes of Staphylococcus aureus infection.
Ige, elevated level of
MedGen UID:
116018
Concept ID:
C0236175
Finding
An abnormally increased overall level of immunoglobulin E in blood.
Craniosynostosis syndrome
MedGen UID:
1163
Concept ID:
C0010278
Disease or Syndrome
A congenital disorder characterized by earlier than normal closure of some or all sutures of the infant skull.
Recurrent fractures
MedGen UID:
42094
Concept ID:
C0016655
Injury or Poisoning
Injuries involving the breaking of either several bones or one bone in two or more places.
Osteopenia
MedGen UID:
18222
Concept ID:
C0029453
Disease or Syndrome
Decreased calcification or density of bone tissue.
Scoliosis
MedGen UID:
11348
Concept ID:
C0036439
Disease or Syndrome
A congenital or acquired spinal deformity characterized by lateral curvature of the spine.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
A skeletal deformity characterized by an unusually prominent forehead. Causes include acromegaly, Hurler syndrome, Silver-Russell syndrome, and thalassemia major.
Joint hypermobility
MedGen UID:
336793
Concept ID:
C1844820
Finding
Craniosynostosis syndrome
MedGen UID:
1163
Concept ID:
C0010278
Disease or Syndrome
A congenital disorder characterized by earlier than normal closure of some or all sutures of the infant skull.
Frontal bossing
MedGen UID:
67453
Concept ID:
C0221354
Congenital Abnormality
A skeletal deformity characterized by an unusually prominent forehead. Causes include acromegaly, Hurler syndrome, Silver-Russell syndrome, and thalassemia major.
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).
Persistence of primary teeth
MedGen UID:
75597
Concept ID:
C0266050
Disease or Syndrome
Persistence of the primary teeth beyond the age by which they normally are shed and replaced by the permanent 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.
Prominent forehead
MedGen UID:
373291
Concept ID:
C1837260
Finding
Forward prominence of the entire forehead, due to protrusion of the frontal bone.
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Chronic mucocutaneous candidiasis
MedGen UID:
2426
Concept ID:
C0006845
Disease or Syndrome
A clinical syndrome characterized by development, usually in infancy or childhood, of a chronic, often widespread candidiasis of skin, nails, and mucous membranes. It may be secondary to one of the immunodeficiency syndromes, inherited as an autosomal recessive trait, or associated with defects in cell-mediated immunity, endocrine disorders, dental stomatitis, or malignancy.
Skin rash
MedGen UID:
8732
Concept ID:
C0015230
Finding
A widespread, acute rash.
Erythema
MedGen UID:
11999
Concept ID:
C0041834
Disease or Syndrome
Red discoloration of the skin caused by infectious agents, inflammation, drug hypersensitivity, or underlying disease.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (145410), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Ige, elevated level of
MedGen UID:
116018
Concept ID:
C0236175
Finding
An abnormally increased overall level of immunoglobulin E in blood.

Recent clinical studies

Etiology

Fan H, Huang L, Yang D, Lin Y, Lu G, Xie Y, Yu J, Zhang D
Medicine (Baltimore) 2018 Apr;97(14):e0215. doi: 10.1097/MD.0000000000010215. PMID: 29620631Free PMC Article
Martin S, Wolters P, Billings N, Toledo-Tamula MA, Hammoud DA, Welch P, Darnell D, Holland SM, Freeman AF
J Clin Immunol 2013 Oct;33(7):1175-84. Epub 2013 Aug 21 doi: 10.1007/s10875-013-9932-z. PMID: 23963745Free PMC Article
Erbagci Z
Pediatr Dermatol 2008 Jan-Feb;25(1):28-33. doi: 10.1111/j.1525-1470.2007.00577.x. PMID: 18304149
Freeman AF, Collura-Burke CJ, Patronas NJ, Ilcus LS, Darnell D, Davis J, Puck JM, Holland SM
Pediatrics 2007 May;119(5):e1121-5. Epub 2007 Apr 16 doi: 10.1542/peds.2006-2649. PMID: 17438082
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

Diagnosis

Hakim A, Bazan IS, Sanogo ML, Manning EP, Pollak JS, Chupp GL
BMC Pulm Med 2019 Feb 8;19(1):34. doi: 10.1186/s12890-019-0797-7. PMID: 30736787Free PMC Article
Fan H, Huang L, Yang D, Lin Y, Lu G, Xie Y, Yu J, Zhang D
Medicine (Baltimore) 2018 Apr;97(14):e0215. doi: 10.1097/MD.0000000000010215. PMID: 29620631Free PMC Article
Battaloglu B, Colak C, Disli OM, Akca B, Erdil N, Karakurt C
Ann Thorac Surg 2017 Jan;103(1):e65-e67. doi: 10.1016/j.athoracsur.2016.06.021. PMID: 28007278
Araya N, Inose H, Kato T, Saito M, Sumiya S, Yamada T, Yoshii T, Kawabata S, Okawa A
J Neurosurg Spine 2014 Aug;21(2):292-5. Epub 2014 May 16 doi: 10.3171/2014.4.SPINE13629. PMID: 24836661
Freeman AF, Collura-Burke CJ, Patronas NJ, Ilcus LS, Darnell D, Davis J, Puck JM, Holland SM
Pediatrics 2007 May;119(5):e1121-5. Epub 2007 Apr 16 doi: 10.1542/peds.2006-2649. PMID: 17438082

Therapy

Karakoc-Aydiner E, Baris S, Keles S, Ozdemir C, Chatila T, Barlan I
J Investig Allergol Clin Immunol 2013;23(5):359-61. PMID: 24260982
Yokota K, Kanemitsu T, Igaki N
Intern Med 2013;52(20):2367-70. doi: 10.2169/internalmedicine.52.0751. PMID: 24126402
Powers AE, Bender JM, Kumánovics A, Ampofo K, Augustine N, Pavia AT, Hill HR
Pediatr Infect Dis J 2009 Jul;28(7):664-6. doi: 10.1097/INF.0b013e31819866ec. PMID: 19483664
Erbagci Z
Pediatr Dermatol 2008 Jan-Feb;25(1):28-33. doi: 10.1111/j.1525-1470.2007.00577.x. PMID: 18304149
Fuller K, Pearce A, Raftos J
Clin Exp Dermatol 2007 Jul;32(4):391-4. Epub 2007 Mar 14 doi: 10.1111/j.1365-2230.2007.02394.x. PMID: 17362234

Prognosis

Fan H, Huang L, Yang D, Lin Y, Lu G, Xie Y, Yu J, Zhang D
Medicine (Baltimore) 2018 Apr;97(14):e0215. doi: 10.1097/MD.0000000000010215. PMID: 29620631Free PMC Article
Martin S, Wolters P, Billings N, Toledo-Tamula MA, Hammoud DA, Welch P, Darnell D, Holland SM, Freeman AF
J Clin Immunol 2013 Oct;33(7):1175-84. Epub 2013 Aug 21 doi: 10.1007/s10875-013-9932-z. PMID: 23963745Free PMC Article
Erbagci Z
Pediatr Dermatol 2008 Jan-Feb;25(1):28-33. doi: 10.1111/j.1525-1470.2007.00577.x. PMID: 18304149
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
DeWitt CA, Bishop AB, Buescher LS, Stone SP
J Am Acad Dermatol 2006 May;54(5):855-65. doi: 10.1016/j.jaad.2005.10.022. PMID: 16635666

Clinical prediction guides

Fan H, Huang L, Yang D, Lin Y, Lu G, Xie Y, Yu J, Zhang D
Medicine (Baltimore) 2018 Apr;97(14):e0215. doi: 10.1097/MD.0000000000010215. PMID: 29620631Free PMC Article
Wolach O, Kuijpers T, Ben-Ari J, Gavrieli R, Feinstein-Goren N, Alders M, Garty BZ, Wolach B
J Clin Immunol 2014 Feb;34(2):163-70. Epub 2014 Jan 23 doi: 10.1007/s10875-014-9988-4. PMID: 24452316
Martin S, Wolters P, Billings N, Toledo-Tamula MA, Hammoud DA, Welch P, Darnell D, Holland SM, Freeman AF
J Clin Immunol 2013 Oct;33(7):1175-84. Epub 2013 Aug 21 doi: 10.1007/s10875-013-9932-z. PMID: 23963745Free 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
van de Veerdonk FL, Marijnissen RJ, Joosten LA, Kullberg BJ, Drenth JP, Netea MG, van der Meer JW
Clin Exp Immunol 2010 Jan;159(1):57-64. Epub 2009 Oct 30 doi: 10.1111/j.1365-2249.2009.04043.x. PMID: 19878510Free PMC Article

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