Information on HIES4B

Basic details

Name: Hyper-IgE recurrent infection syndrome 4B | Acronym: HIES4B
Alt. names: IL6 signal transducer (complete) deficiency

Gene: IL6ST | MOI: Autosomal recessive | Mechanism of action: Loss of Function

No. of cases in DB: 3 | First reported in: 2017

Last updated on: 2023-04-01 05:00:09 by Xiao P. Peng

OMIM: 618523

Orphanet: -

MONDO: -

DOID: -

ClinGen:

Description

Thus far, only three unrelated patients have been reported with this recessive form of HIES characterized by early onset recurrent infections affecting the sinorespiratory tract, skin, and eyes, severe atopy including eczema, asthma and allergies, retarded growth and development, recurrent diarrhea, pain insensitivity, and musculoskeletal abnormalities. The last includes craniofacial dysmorphisms (i.e. craniosynostosis, midface retrusion, high arched palate, telecanthus, long palpebral fissures, prominent lower jaw, retained primary teeth), progressive thoracolumbar scoliosis, increased fracture susceptibility, congenital distal contractures, foot deformities, and destructive arthropathy (PMID: 28747427, 30309848, 33771552). Cardiopulmonary complications include the development of pneumothoraces, bronchiectasis and pulmonary hypertension. Immunophenotyping is notable for elevated IgE levels, peripheral eosinophilia, defective B cell memory, loss of Th1 polarization, and impaired acute-phase responses (PMID: 28747427).

Management

Currently treatment is symptomatic. Anti-microbial prophylaxis and/or Ig supplementation may be considered given the infectious risks. Dupilumab has been used successfully to treat individuals with other forms of HIES.

3 reported cases added to GenIA

SubjectID	Sex	Fam.ID	AD	Country	Population	Reference & Pub.code
102410	F	214947	7		South Asian	PMID:28747427 [Fam.A:II.3(P1)]
102474	M	214963	8	U.S.A.	Admixed	PMID:33771552 [Patient(II.1)]
102477	M	214964	12	Turkey	Turkish	PMID:30309848 [Patient(III.5)]

AD: Age at genetic diagnosis; AFM: age at first manifestation; PMID: PubMed ID; GRID: GenIA reference ID (ref. not in PubMed).

Summary of clinical findings

[Considering only Definitive and Possible cases]

Rank	Clinical term	Present	Absent	Unreported
1	Eosinophilia	3 (99.9%)	0 (0.0%)	0 (0.0%)
2	(unusual) Respiratory tract infection	3 (99.9%)	0 (0.0%)	0 (0.0%)
3	Craniosynostosis	3 (99.9%)	0 (0.0%)	0 (0.0%)
4	Increased IgE levels	3 (99.9%)	0 (0.0%)	0 (0.0%)
5	Lung disease	3 (99.9%)	0 (0.0%)	0 (0.0%)
6	Pneumonia	3 (99.9%)	0 (0.0%)	0 (0.0%)
7	Otitis media	2 (66.7%)	0 (0.0%)	1 (33.3%)
8	Increased proportion of naive B cells	2 (66.7%)	0 (0.0%)	1 (33.3%)
9	Atopy	2 (66.7%)	0 (0.0%)	1 (33.3%)
10	Allergy	2 (66.7%)	0 (0.0%)	1 (33.3%)
11	Food allergy	2 (66.7%)	0 (0.0%)	1 (33.3%)
12	Hypogammaglobulinemia	2 (66.7%)	0 (0.0%)	1 (33.3%)
13	Eczema	2 (66.7%)	0 (0.0%)	1 (33.3%)
14	Retained primary teeth	2 (66.7%)	0 (0.0%)	1 (33.3%)
15	Decreased proportion of switched memory B cells	1 (33.3%)	0 (0.0%)	2 (66.7%)
16	Decreased IgA levels	1 (33.3%)	0 (0.0%)	2 (66.7%)
17	Mandibular prognathia	1 (33.3%)	0 (0.0%)	2 (66.7%)
18	Decreased proportion of unswitched memory B cells	1 (33.3%)	0 (0.0%)	2 (66.7%)
19	Telecanthus	1 (33.3%)	0 (0.0%)	2 (66.7%)
20	Long palpebral fissure	1 (33.3%)	0 (0.0%)	2 (66.7%)
21	Recurrent upper respiratory tract infection	1 (33.3%)	0 (0.0%)	2 (66.7%)
22	Delayed eruption of teeth	1 (33.3%)	0 (0.0%)	2 (66.7%)
23	Periorbital edema	1 (33.3%)	0 (0.0%)	2 (66.7%)
24	Decreased proportion of central memory CD4-T cells	1 (33.3%)	0 (0.0%)	2 (66.7%)
25	Septicaemia	1 (33.3%)	0 (0.0%)	2 (66.7%)
26	Global developmental delay	1 (33.3%)	0 (0.0%)	2 (66.7%)
27	Decreased IgM levels	1 (33.3%)	1 (33.3%)	1 (33.3%)
28	Reduced number of B cells	1 (33.3%)	1 (33.3%)	1 (33.3%)
29	Pulmonary arterial hypertension	1 (33.3%)	0 (0.0%)	2 (66.7%)
30	Increased IgM levels	1 (33.3%)	0 (0.0%)	2 (66.7%)
31	Increased susceptibility to fractures	1 (33.3%)	0 (0.0%)	2 (66.7%)
32	short stature	1 (33.3%)	0 (0.0%)	2 (66.7%)
33	Bronchiectasis	1 (33.3%)	0 (0.0%)	2 (66.7%)
34	Hip dislocation	1 (33.3%)	0 (0.0%)	2 (66.7%)
35	Elbow flexion contracture	1 (33.3%)	0 (0.0%)	2 (66.7%)
36	Skeletal system abnormality	1 (33.3%)	0 (0.0%)	2 (66.7%)
37	Arthropathy	1 (33.3%)	0 (0.0%)	2 (66.7%)
38	Scoliosis	1 (33.3%)	0 (0.0%)	2 (66.7%)
39	Pneumothorax	1 (33.3%)	0 (0.0%)	2 (66.7%)
40	Congenital finger flexion contractures	1 (33.3%)	0 (0.0%)	2 (66.7%)
41	Osteomyelitis	1 (33.3%)	0 (0.0%)	2 (66.7%)
42	Psychomotor retardation	1 (33.3%)	0 (0.0%)	2 (66.7%)
43	Progressive congenital scoliosis	1 (33.3%)	0 (0.0%)	2 (66.7%)
44	(unusual) Fungal infection	1 (33.3%)	0 (0.0%)	2 (66.7%)
45	Pleural empyema	1 (33.3%)	0 (0.0%)	2 (66.7%)
46	Infective Arthritis	1 (33.3%)	0 (0.0%)	2 (66.7%)
47	Increased IgA levels	1 (33.3%)	0 (0.0%)	2 (66.7%)
48	Keratitis	1 (33.3%)	0 (0.0%)	2 (66.7%)
49	Increased proportion of effector mem. CD4 T cells	1 (33.3%)	0 (0.0%)	2 (66.7%)
50	Sleep apnea	1 (33.3%)	0 (0.0%)	2 (66.7%)
51	High palate	1 (33.3%)	0 (0.0%)	2 (66.7%)
52	Pneumatocele	1 (33.3%)	0 (0.0%)	2 (66.7%)
53	Midface retrusion	1 (33.3%)	0 (0.0%)	2 (66.7%)
54	Asthma	1 (33.3%)	0 (0.0%)	2 (66.7%)
55	Corneal ulceration	1 (33.3%)	0 (0.0%)	2 (66.7%)
56	Decreased IgG levels	0 (0.0%)	1 (33.3%)	2 (66.7%)
57	Reduced NK cell number	0 (0.0%)	1 (33.3%)	2 (66.7%)
58	Lymphopenia	0 (0.0%)	2 (66.7%)	1 (33.3%)
59	Reduced proportion of CD8 T cells	0 (0.0%)	1 (33.3%)	2 (66.7%)
60	Reduced T cell count	0 (0.0%)	2 (66.7%)	1 (33.3%)
61	Reduced proportion of CD4 T cells	0 (0.0%)	1 (33.3%)	2 (66.7%)

Summary of treatment outcomes

[Considering only Definitive and Possible cases]

Treatment ⓘ	Responses & clinical indications