Information on HIES2
Name: Hyper-IgE recurrent infection syndrome 2 | Acronym: HIES2
Alt. names: DOCK8 deficiency | Hyper-IgE syndrome 2
Gene: DOCK8 | MOI: Autosomal recessive | Mechanism of action: Loss of Function
No. of cases in DB: 31 | First reported in: 2009
Last updated on: 2023-02-28 by
Description
HIES syndrome caused by biallelic mutations in DOCK8. Individuals may also be at higher risk of oncologic complications, including lymphoma and squamous cell carcinomas.
Management
Antiinfectious prophylaxis and early and aggressive treatment of infections can be beneficial. Awareness and surveillance may be beneficial in order to allow early detection of oncologic complications and treatment. HSCT has been described.
Please mind that full curation of this condition has not been completed yet. It is currently ongoing.
Summary of clinical findings
[Considering only Definitive and Possible cases]
| Rank | Clinical phenotype | Present | Absent | Unreported |
|---|---|---|---|---|
| 1 | Abnormal circulating IgE level |
25 (89.3%) | 1 (3.6%) | 2 (7.1%) |
| 2 | Increased IgE levels |
25 (89.3%) | 1 (3.6%) | 2 (7.1%) |
| 3 | Hypergammaglobulinaemia |
25 (89.3%) | 1 (3.6%) | 2 (7.1%) |
| 4 | Dermatitis |
24 (85.7%) | 0 (0.0%) | 4 (14.3%) |
| 5 | Eczema |
23 (82.1%) | 0 (0.0%) | 5 (17.9%) |
| 6 | Eosinophilia |
22 (78.6%) | 2 (7.1%) | 4 (14.3%) |
| 7 | Leukocytosis |
22 (78.6%) | 2 (7.1%) | 4 (14.3%) |
| 8 | Abnormal eosinophil count |
22 (78.6%) | 2 (7.1%) | 4 (14.3%) |
| 9 | Increased inflammatory response |
18 (64.3%) | 0 (0.0%) | 10 (35.7%) |
| 10 | (unusual) Respiratory tract infection |
16 (57.1%) | 0 (0.0%) | 12 (42.9%) |
| 11 | Lung disease |
15 (53.6%) | 0 (0.0%) | 13 (46.4%) |
| 12 | Pneumonia |
15 (53.6%) | 0 (0.0%) | 13 (46.4%) |
| 13 | Abscess |
12 (42.9%) | 0 (0.0%) | 16 (57.1%) |
| 14 | Recurrent upper respiratory tract infections |
11 (39.3%) | 0 (0.0%) | 17 (60.7%) |
| 15 | Cutaneous abscess |
11 (39.3%) | 0 (0.0%) | 17 (60.7%) |
| 16 | Skin rash |
10 (35.7%) | 0 (0.0%) | 18 (64.3%) |
| 17 | Enteropathy |
9 (32.1%) | 0 (0.0%) | 19 (67.9%) |
| 18 | Diarrhea |
9 (32.1%) | 0 (0.0%) | 19 (67.9%) |
| 19 | Abdominal symptom |
9 (32.1%) | 0 (0.0%) | 19 (67.9%) |
| 20 | Otitis media |
7 (25.0%) | 0 (0.0%) | 21 (75.0%) |
| 21 | Abnormal paranasal sinus morphology |
6 (21.4%) | 0 (0.0%) | 22 (78.6%) |
| 22 | Sinusitis |
6 (21.4%) | 0 (0.0%) | 22 (78.6%) |
| 23 | obstructive lung disease |
6 (21.4%) | 1 (3.6%) | 21 (75.0%) |
| 24 | Mucocutaneous candidiasis |
5 (17.9%) | 0 (0.0%) | 23 (82.1%) |
| 25 | Unusual virus reactivation |
5 (17.9%) | 0 (0.0%) | 23 (82.1%) |
| 26 | Abnormal lymphoproliferation |
5 (17.9%) | 0 (0.0%) | 23 (82.1%) |
| 27 | Visceromegaly |
5 (17.9%) | 0 (0.0%) | 23 (82.1%) |
| 28 | Herpes Simplex Virus Infection |
5 (17.9%) | 0 (0.0%) | 23 (82.1%) |
| 29 | Atopy |
5 (17.9%) | 0 (0.0%) | 23 (82.1%) |
| 30 | Recurrent viral infections |
5 (17.9%) | 0 (0.0%) | 23 (82.1%) |
| 31 | (unusual) Viral infection |
5 (17.9%) | 0 (0.0%) | 23 (82.1%) |
| 32 | Abnormal bronchus morphology |
4 (14.3%) | 1 (3.6%) | 23 (82.1%) |
| 33 | (unusual) Skin infection |
4 (14.3%) | 0 (0.0%) | 24 (85.7%) |
| 34 | Abnormal liver morphology |
4 (14.3%) | 0 (0.0%) | 24 (85.7%) |
| 35 | Bronchiectasis |
4 (14.3%) | 1 (3.6%) | 23 (82.1%) |
| 36 | Warts |
4 (14.3%) | 0 (0.0%) | 24 (85.7%) |
| 37 | Frequent skin infections |
4 (14.3%) | 0 (0.0%) | 24 (85.7%) |
| 38 | Abnormal proportion of CD4 T cells |
4 (14.3%) | 0 (0.0%) | 24 (85.7%) |
| 39 | Papilloma |
4 (14.3%) | 0 (0.0%) | 24 (85.7%) |
| 40 | Abnormal spleen morphology |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 41 | Abnormality of the middle ear |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 42 | Hepatopathy |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 43 | Abnormal circulating IgM level |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 44 | Lymphopenia |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 45 | Decreased IgM levels |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 46 | Recurrent respiratory infections |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 47 | Splenomegaly |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 48 | Suppurative Otitis Media |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 49 | Decreased body weight |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 50 | Hepatomegaly |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 51 | Reduced T cell count |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 52 | Abnormality of dental eruption |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 53 | Abnormality of primary teeth |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 54 | Failure to thrive |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 55 | Onychomycosis |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 56 | Hypogammaglobulinemia |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 57 | Abnormal T cell count |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 58 | Reduced proportion of CD4 T cells |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 59 | Abnormality of the dentition |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 60 | Retained primary teeth |
3 (10.7%) | 0 (0.0%) | 25 (89.3%) |
| 61 | Unusual infection by anatomical site |
2 (7.1%) | 0 (0.0%) | 26 (92.9%) |
| 62 | Atopic dermatitis |
2 (7.1%) | 0 (0.0%) | 26 (92.9%) |
| 63 | Recurrent lower respiratory tract infections |
2 (7.1%) | 0 (0.0%) | 26 (92.9%) |
| 64 | Cow milk allergy |
2 (7.1%) | 0 (0.0%) | 26 (92.9%) |
| 65 | Dairy allergy |
2 (7.1%) | 0 (0.0%) | 26 (92.9%) |
| 66 | Abnormal proportion of naive CD4 T cells |
2 (7.1%) | 0 (0.0%) | 26 (92.9%) |
| 67 | Candidiasis |
2 (7.1%) | 0 (0.0%) | 26 (92.9%) |
| 68 | Abnormal respiratory system physiology |
2 (7.1%) | 0 (0.0%) | 26 (92.9%) |
| 69 | Reduced proportion of naive CD4 T cells |
2 (7.1%) | 0 (0.0%) | 26 (92.9%) |
| 70 | Reduced proportion of naive T cells |
2 (7.1%) | 0 (0.0%) | 26 (92.9%) |
| 71 | Candida Onychomycosis |
2 (7.1%) | 0 (0.0%) | 26 (92.9%) |
| 72 | Asthma |
2 (7.1%) | 0 (0.0%) | 26 (92.9%) |
| 73 | Abnormal nervous system physiology |
2 (7.1%) | 0 (0.0%) | 26 (92.9%) |
| 74 | Reduced proportion of naive CD8 T cells |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 75 | Decreased proportion of switched memory B cells |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 76 | Erythematous plaque |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 77 | Abnormal palate morphology |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 78 | Decreased proportion of memory B cells |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 79 | Abnormal proportion of class-switched memory B cells |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 80 | Decreased IgA levels |
1 (3.6%) | 1 (3.6%) | 26 (92.9%) |
| 81 | Abnormality of the mastoid |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 82 | Negative ab-response to vaccination |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 83 | Chronic otitis media |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 84 | Seizures |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 85 | Abnormal immune system morphology |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 86 | Opportunistic fungal infection |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 87 | Increased blood pressure |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 88 | B-cell lymphoma |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 89 | Lymphadenopathy |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 90 | Skin plaque |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 91 | Recurrent upper and lower respiratory tract infections |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 92 | Abnormal circulating IgA level |
1 (3.6%) | 1 (3.6%) | 26 (92.9%) |
| 93 | Abnormal circulating IgG level |
1 (3.6%) | 1 (3.6%) | 26 (92.9%) |
| 94 | Decreased specific antibody response to polysaccharide vaccine |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 95 | House dust mite allergy |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 96 | Egg allergy |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 97 | Nut food product allergy |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 98 | Plant based food allergy |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 99 | Increased proportion of CD8+ TEMRA T cells |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 100 | Exanthem |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 101 | Abnormal abdomen morphology |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 102 | Infectious meningitis |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 103 | Severe viral infection |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 104 | Bacterial meningitis |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 105 | Pruritus |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 106 | Skin abnormality |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 107 | Recurrent impetigo |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 108 | Pain |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 109 | Esophageal candidiasis |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 110 | Allergy |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 111 | Neoplasm of the skin |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 112 | Dust mite allergy |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 113 | Food allergy |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 114 | Varicella zoster virus infection |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 115 | Maculopapular exanthema |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 116 | Non-Hodgkin lymphoma |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 117 | Herpes labialis, recurrent |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 118 | Unusual infection |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 119 | (unusual) Fungal infection |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 120 | Reduced ab-response to pneumococcal polysaccharide vaccine |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 121 | Increased IgG level |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 122 | Cervical lymphadenopathy |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 123 | Abnormal lymphocyte count |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 124 | Arthritis |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 125 | Abnormal B cell count |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 126 | Infective Arthritis |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 127 | Ascites |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 128 | Headaches |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 129 | Liver abscess |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 130 | Actinic keratosis |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 131 | Seborrheic keratosis |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 132 | Abnormality of skin physiology |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 133 | Hypertension |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 134 | Increased proportion of effector mem. CD4 T cells |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 135 | Mastoiditis |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 136 | Abnormality of the mouth |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 137 | Pyoderma |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 138 | High palate |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 139 | Neoplasm by anatomical site |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 140 | Increased proportion of CD8 memory T cells |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 141 | Increased proportion of CD4 memory T cells |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 142 | Facial abnormality |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 143 | Facial dysmorphism |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 144 | Abnormal proportion of CD8-positive, alpha-beta TEMRA T cells |
1 (3.6%) | 0 (0.0%) | 27 (96.4%) |
| 145 | Decreased IgG levels |
0 (0.0%) | 1 (3.6%) | 27 (96.4%) |
| 146 | Pulmonary cyst |
0 (0.0%) | 1 (3.6%) | 27 (96.4%) |
| 147 | Pneumatocele |
0 (0.0%) | 1 (3.6%) | 27 (96.4%) |
Age of onset
distribution
Please mind that full curation of this condition has not been completed yet. It is currently ongoing.
Summary of treatment outcomes
[Considering only Definitive and Possible cases]
| Treatment ⓘ | Responses & clinical indications |
|---|---|
| Antihistamines | Absent (2) for Atopic dermatitis; Pruritus |
| Immunosuppressive agents | Absent (1) for Atopic dermatitis. Mild (1) for Eczema |
| Corticosteroids [Immunosuppressive agents] [Anti-Inflammatory agents] |
Absent (1) for Atopic dermatitis. Mild (1) for Eczema |
| Acyclovir [Antiviral agent] |
Moderate (1) for Herpes Simplex Virus Infection. Unspecified (1) for Herpes Simplex Virus Infection |
| Intravenous immunoglobulin therapy | Absent (2) for Atopic dermatitis; Herpes Simplex Virus Infection & Pneumonia. Good (1) for Frequent skin infections & Recurrent upper and lower respiratory tract infections |
| Antibiotics | Absent (1) for Diarrhea. Unspecified (1) for Frequent skin infections |
| Antifungal agents | Unspecified (1) for Esophageal candidiasis |
| Antiviral agent | Moderate (1) for Herpes Simplex Virus Infection. Unspecified (1) for Herpes Simplex Virus Infection |
| Diet | Absent (1) for Atopic dermatitis & Diarrhea. Good (1) for Cow milk allergy |
Please mind that full curation of this condition has not been completed yet. It is currently ongoing.
31 reported cases added to GenIA
| SubjectID | Sex | Fam.ID | AD | AFM | Validity | Country | Population | Reference & Pub.code |
|---|---|---|---|---|---|---|---|---|
| 101153 |
M | 210757 | 41 | German | PMID:34390440 [HIES55] | |||
| 101191 |
M | 212375 | 4 | Egypt | Egyptian | PMID:34390440 [HIES14] | ||
| 101195 |
F | 212379 | 4 | Egypt | Egyptian | PMID:34390440 [HIES19] | ||
| 101197 |
F | 214344 | 8 | Egypt | Egyptian | PMID:34390440 [HIES18] | ||
| 101580 |
M | 212601 | 14 | Iran | Iranian | PMID:34390440 [HIES17] | ||
| 101894 |
M | 212285 | Italy | Italian | PMID:34390440 [NEG049] | |||
| 101904 |
F | 212312 | United Kingdom | British | PMID:34390440 [HIES09] | |||
| 101982 |
F | 214072 | 15 | Omani | PMID:34390440 [HIES06] | |||
| 102031 |
M | 214221 | 15 | Iran | PMID:34390440 [HIES07] | |||
| 102036 |
U | 214243 | PMID:34390440 [NEG134] | |||||
| 102047 |
M | 214258 | 10 | Iran | PMID:34390440 [HIES13] | |||
| 102054 |
F | 214266 | 9 | Turkey | PMID:34390440 [HIES08] | |||
| 102055 |
F | 214273 | 7 | Iran | Iranian | PMID:34390440 [HIES22] | ||
| 102057 |
M | 214275 | 11 | Iran | Iranian | PMID:34390440 [HIES25] | ||
| 102065 |
M | 214285 | 10 | Egypt | Egyptian | PMID:34390440 [HIES23] | ||
| 102074 |
F | 214294 | 7 | Egypt | Egyptian | PMID:34390440 [HIES27]; PMID:32738296 [P2] | ||
| 102076 |
M | 214296 | 3 | Egypt | Egyptian | PMID:34390440 [HIES24] | ||
| 102077 |
F | 214297 | 6 | Egyptian | PMID:34390440 [HIES10] | |||
| 102082 |
U | 214302 | Egypt | Egyptian | PMID:34390440 [HIES11] | |||
| 102083 |
F | 214302 | 2 | Egypt | Egyptian | PMID:34390440 [NEG168] | ||
| 102084 |
M | 214303 | 4 | Egypt | Egyptian | PMID:34390440 [HIES02] | ||
| 102085 |
M | 214304 | 4 | Egypt | Egyptian | PMID:34390440 [HIES12] | ||
| 102107 |
M | 214329 | 7 | Portugal | Portuguese | PMID:34390440 [HIES26] | ||
| 102116 |
M | 212357 | 4 | Egyptian | PMID:34390440 [HIES05] | |||
| 102117 |
F | 214341 | 4 | Egypt | Egyptian | PMID:34390440 [HIES20] | ||
| 102119 |
M | 214343 | 5 | Egypt | Egyptian | PMID:34390440 [HIES15] | ||
| 102120 |
M | 214344 | 7 | Disputed | Egypt | Egyptian | PMID:34390440 [HIES21] | |
| 102121 |
M | 214345 | 6 | Egypt | Egyptian | PMID:34390440 [HIES16] | ||
| 102144 |
M | 214565 | 10 | Iranian | PMID:34390440 [HIES54] | |||
| 107151 |
M | 216364 |
16 | 4 | Definitive | Turkey | Turkish | PMID:39437980 [Fam.A:II.1(Patient 1)] |
| 107156 |
F | 216365 |
10 | 0 | Definitive | Turkey | Turkish | PMID:39437980 [Fam.B:II.2(Patient 2)] |
AD: Age at genetic diagnosis; AFM: age at first manifestation; PMID: PubMed ID; GRID: GenIA reference ID (ref. not in PubMed).