HIES4
MCID: HYP845
MIFTS: 22

Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive (HIES4)

Categories: Blood diseases, Bone diseases, Genetic diseases, Immune diseases, Rare diseases, Skin diseases

Aliases & Classifications for Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive

MalaCards integrated aliases for Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive:

Name: Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive 56 73 6
Hies4 56 73

Characteristics:

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
two unrelated patients have been reported (last curated july 2019)


HPO:

31
hyper-ige recurrent infection syndrome 4, autosomal recessive:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive

OMIM : 56 Hyper-IgE recurrent infection syndrome-4 (HIES4) is an autosomal recessive immunologic disorder characterized by early childhood onset of recurrent infections and skeletal abnormalities, including craniosynostosis and scoliosis. Patients are susceptible to infections, mainly bacterial infections that affect the respiratory tract, skin, and eye. Immunologic workup shows increased serum IgE, intermittent eosinophilia, and impaired IL6 (147620) and IL27 (608273) downstream signaling that affects the development and function of certain B- and T-cell populations, as well as the acute-phase response; IL11 (147681) signaling in fibroblasts is also affected (summary by Shahin et al., 2019). For a discussion of genetic heterogeneity of hyper-IgE recurrent infection syndrome, see HIES1 (147060). (618523)

MalaCards based summary : Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive, is also known as hies4. An important gene associated with Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive is IL6ST (Interleukin 6 Signal Transducer). Affiliated tissues include t cells, skin and eye, and related phenotypes are macroglossia and recurrent respiratory infections

UniProtKB/Swiss-Prot : 73 Hyper-IgE recurrent infection syndrome 4, autosomal recessive: An immunologic disorder characterized by recurrent infections, mainly affecting the respiratory tract, skin and eye, and skeletal abnormalities including craniosynostosis and scoliosis. Immunologic workup shows increased serum IgE, intermittent eosinophilia, impaired development of certain B- and T-cell populations, as well as impaired acute-phase response. Disease onset is in early childhood.

Related Diseases for Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive

Symptoms & Phenotypes for Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive

Human phenotypes related to Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive:

31 (show all 19)
# Description HPO Frequency HPO Source Accession
1 macroglossia 31 very rare (1%) HP:0000158
2 recurrent respiratory infections 31 very rare (1%) HP:0002205
3 recurrent otitis media 31 very rare (1%) HP:0000403
4 neurodevelopmental delay 31 very rare (1%) HP:0012758
5 dental crowding 31 very rare (1%) HP:0000678
6 hip dislocation 31 very rare (1%) HP:0002827
7 chronic diarrhea 31 very rare (1%) HP:0002028
8 keratitis 31 very rare (1%) HP:0000491
9 eczema 31 very rare (1%) HP:0000964
10 craniosynostosis 31 very rare (1%) HP:0001363
11 eosinophilia 31 very rare (1%) HP:0001880
12 bronchiectasis 31 very rare (1%) HP:0002110
13 arthropathy 31 very rare (1%) HP:0003040
14 joint contracture of the hand 31 very rare (1%) HP:0009473
15 clubbing 31 very rare (1%) HP:0001217
16 thoracolumbar scoliosis 31 very rare (1%) HP:0002944
17 scaphocephaly 31 very rare (1%) HP:0030799
18 increased circulating ige level 31 very rare (1%) HP:0003212
19 food allergy 31 very rare (1%) HP:0500093

Symptoms via clinical synopsis from OMIM:

56
Skeletal Spine:
scoliosis

Head And Neck Head:
prominent forehead
scaphocephaly

Skeletal Pelvis:
hip dislocation

Head And Neck Eyes:
keratitis
ocular infections

Skeletal Skull:
craniosynostosis

Respiratory Lung:
bronchiectasis

Skeletal Hands:
finger contractures

Skeletal Limbs:
elbow contractures

Head And Neck Teeth:
retained teeth

Growth Height:
short stature

Head And Neck Mouth:
high palate

Muscle Soft Tissue:
cellulitis

Skin Nails Hair Skin:
eczema
recurrent skin infections
atopic dermatitis

Abdomen Gastrointestinal:
diarrhea

Neurologic Central Nervous System:
poor speech
developmental delay, mild

Respiratory:
respiratory infections, recurrent

Immunology:
increased ige
recurrent infections, mainly bacterial
eosinophilia, intermittent
decreased class-switched memory b cells
impaired development and function of certain t cell subsets
more

Clinical features from OMIM:

618523

Drugs & Therapeutics for Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive

Search Clinical Trials , NIH Clinical Center for Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive

Genetic Tests for Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive

Anatomical Context for Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive

MalaCards organs/tissues related to Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive:

40
T Cells, Skin, Eye, B Cells

Publications for Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive

Articles related to Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive:

# Title Authors PMID Year
1
Selective loss of function variants in IL6ST cause Hyper-IgE syndrome with distinct impairments of T-cell phenotype and function. 56 6
30309848 2019
2
A biallelic mutation in IL6ST encoding the GP130 co-receptor causes immunodeficiency and craniosynostosis. 56 6
28747427 2017

Variations for Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive

ClinVar genetic disease variations for Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive:

6 ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 IL6ST NM_002184.4(IL6ST):c.1210A>T (p.Asn404Tyr)SNV Pathogenic 638565 5:55251910-55251910 5:55956082-55956082
2 IL6ST NM_002184.4(IL6ST):c.1493C>T (p.Pro498Leu)SNV Pathogenic 638566 5:55248137-55248137 5:55952309-55952309

UniProtKB/Swiss-Prot genetic disease variations for Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive:

73
# Symbol AA change Variation ID SNP ID
1 IL6ST p.Asn404Tyr VAR_083197
2 IL6ST p.Pro498Leu VAR_083198

Expression for Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive

Search GEO for disease gene expression data for Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive.

Pathways for Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive

GO Terms for Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive

Sources for Hyper-Ige Recurrent Infection Syndrome 4, Autosomal Recessive

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72 UMLS via Orphanet
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