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Hyper-IgM syndrome type 4(HIGM4)

MedGen UID:: 330847
•Concept ID:: C1842413
•: Disease or Syndrome

Synonyms:	HIGM4; Immunodeficiency with hyper IgM type 4

Monarch Initiative:	MONDO:0011985
OMIM®:	608184
Orphanet:	ORPHA101091

Definition

Hyper-IgM syndrome is a condition characterized by normal or increased serum IgM concentrations associated with low or absent serum IgG, IgA, and IgE concentrations, indicating a defect in the class-switch recombination (CSR) process (summary by Imai et al., 2003). For a discussion of genetic heterogeneity of immunodeficiency with hyper-IgM, see HIGM1 (308230). [from OMIM]

Clinical features

From HPO

Myelodysplasia

MedGen UID:: 10231
•Concept ID:: C0026985
•: Congenital Abnormality

Clonal hematopoietic stem cell disorders characterized by dysplasia (ineffective production) in one or more hematopoietic cell lineages, leading to anemia and cytopenia.

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Recurrent infection of the gastrointestinal tract

MedGen UID:: 343135
•Concept ID:: C1854495
•: Disease or Syndrome

Recurrent infection of the gastrointestinal tract.

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Bronchiectasis

MedGen UID:: 14234
•Concept ID:: C0006267
•: Disease or Syndrome

Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways.

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Recurrent upper respiratory tract infections

MedGen UID:: 154380
•Concept ID:: C0581381
•: Disease or Syndrome

An increased susceptibility to upper respiratory tract infections as manifested by a history of recurrent upper respiratory tract infections (running ears - otitis, sinusitis, pharyngitis, tonsillitis).

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Autoimmune hemolytic anemia

MedGen UID:: 1918
•Concept ID:: C0002880
•: Disease or Syndrome

An autoimmune form of hemolytic anemia.

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Immunodeficiency

MedGen UID:: 7034
•Concept ID:: C0021051
•: Disease or Syndrome

Failure of the immune system to protect the body adequately from infection, due to the absence or insufficiency of some component process or substance.

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Osteomyelitis

MedGen UID:: 10497
•Concept ID:: C0029443
•: Disease or Syndrome

Osteomyelitis is an inflammatory process accompanied by bone destruction and caused by an infecting microorganism.

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Autoimmune thrombocytopenia

MedGen UID:: 116621
•Concept ID:: C0242584
•: Disease or Syndrome

The presence of thrombocytopenia in combination with detection of antiplatelet antibodies.

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Impaired Ig class switch recombination

MedGen UID:: 374953
•Concept ID:: C1842528
•: Finding

An impairment of the class-switch recombination process that normally leads B lymphocytes to produce IgG, IgA, or IgE.

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Recurrent bacterial infections

MedGen UID:: 334943
•Concept ID:: C1844383
•: Finding

Increased susceptibility to bacterial infections, as manifested by recurrent episodes of bacterial infection.

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Absence of lymph node germinal center

MedGen UID:: 376112
•Concept ID:: C1847383
•: Finding

Absence of germinal centers in lymph nodes. Germinal centers are the parts of lymph nodes in which B lymphocytes proliferate, differentiate, mutate through somatic hypermutation and class switch during antibody responses.

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Abnormality of the digestive system
- Recurrent infection of the gastrointestinal tract
Abnormality of the immune system
Abnormality of the respiratory system
- Bronchiectasis
- Recurrent upper respiratory tract infections
Neoplasm
- Myelodysplasia

Term Hierarchy

GTR
MeSH
Orphanet

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVHyper-IgM syndrome type 4

Immunodeficiency with severe reduction in serum IgG and IgA with normal/elevated IgM and normal number of B-cells
- Hyper-IgM syndrome without susceptibility to opportunistic infections
  - Hyper-IgM syndrome type 4

Follow this link to review classifications for Hyper-IgM syndrome type 4 in Orphanet.

Professional guidelines

PubMed

Low Rates of Poliovirus Antibodies in Primary Immunodeficiency Patients on Regular Intravenous Immunoglobulin Treatment.

Costa-Carvalho BT, Sullivan KE, Fontes PM, Aimé-Nobre F, Gonzales IGS, Lima ES, Granato C, de Moraes-Pinto MI
J Clin Immunol 2018 Jul;38(5):628-634. Epub 2018 Jul 14 doi: 10.1007/s10875-018-0531-x. PMID: 30006913

See all (1)

Recent clinical studies

Etiology

Clinical features and hematopoietic stem cell transplantations for CD40 ligand deficiency in Japan.

Mitsui-Sekinaka K, Imai K, Sato H, Tomizawa D, Kajiwara M, Nagasawa M, Morio T, Nonoyama S
J Allergy Clin Immunol 2015 Oct;136(4):1018-24. Epub 2015 Mar 31 doi: 10.1016/j.jaci.2015.02.020. PMID: 25840720

Pediatric allergy and immunology in Brazil.

Rosario-Filho NA, Jacob CM, Sole D, Condino-Neto A, Arruda LK, Costa-Carvalho B, Cocco RR, Camelo-Nunes I, Chong-Neto HJ, Wandalsen GF, Castro AP, Yang AC, Pastorino AC, Sarinho ES
Pediatr Allergy Immunol 2013 Jun;24(4):402-9. Epub 2013 Apr 11 doi: 10.1111/pai.12069. PMID: 23578336

Clinical manifestations and outcomes of pediatric chronic neutropenia.

Wan C, Yu HH, Lu MY, Lee JH, Wang LC, Lin YT, Yang YH, Chiang BL
J Formos Med Assoc 2012 Apr;111(4):220-7. Epub 2012 Mar 16 doi: 10.1016/j.jfma.2010.12.003. PMID: 22526211

Study of patients with Hyper-IgM type IV phenotype who recovered spontaneously during late childhood and review of the literature.

Karaca NE, Durandy A, Gulez N, Aksu G, Kutukculer N
Eur J Pediatr 2011 Aug;170(8):1039-47. Epub 2011 Jan 28 doi: 10.1007/s00431-011-1400-2. PMID: 21274562

Hematopoietic cell transplantation for correction of primary immunodeficiencies.

Filipovich A
Bone Marrow Transplant 2008 Aug;42 Suppl 1:S49-S52. doi: 10.1038/bmt.2008.121. PMID: 18724301

See all (10)

Diagnosis

B Cell Disorders in Children: Part II.

Griffin DD, Dolen WK
Curr Allergy Asthma Rep 2020 Aug 21;20(11):64. doi: 10.1007/s11882-020-00963-z. PMID: 32821980

CD40 Ligand Deficiency.

Leite LFB, Máximo TA, Mosca T, Forte WCN
Allergol Immunopathol (Madr) 2020 Jul-Aug;48(4):409-413. Epub 2019 Dec 9 doi: 10.1016/j.aller.2019.08.005. PMID: 31831191

Clinical and molecular features of X-linked hyper IgM syndrome - An experience from North India.

Rawat A, Mathew B, Pandiarajan V, Jindal A, Sharma M, Suri D, Gupta A, Goel S, Karim A, Saikia B, Minz RW, Imai K, Nonoyama S, Ohara O, Giliani SC, Notarangelo LD, Chan KW, Lau YL, Singh S
Clin Immunol 2018 Oct;195:59-66. Epub 2018 Jul 25 doi: 10.1016/j.clim.2018.07.013. PMID: 30053428 Free PMC Article

X-linked hyper-IgM syndrome with CD40LG mutation: two case reports and literature review in Taiwanese patients.

Tsai HY, Yu HH, Chien YH, Chu KH, Lau YL, Lee JH, Wang LC, Chiang BL, Yang YH
J Microbiol Immunol Infect 2015 Feb;48(1):113-8. Epub 2012 Sep 24 doi: 10.1016/j.jmii.2012.07.004. PMID: 23010537

Pediatric allergy and immunology in Brazil.

See all (25)

Therapy

A Novel CD40L Mutation Associated with X-Linked Hyper IgM Syndrome in a Chinese Family.

Li L, Ji J, Han M, Xu Y, Zhang X, Liu W, Liu S
Immunol Invest 2020 Apr;49(3):307-316. Epub 2019 Aug 12 doi: 10.1080/08820139.2019.1638397. PMID: 31401902

Low Rates of Poliovirus Antibodies in Primary Immunodeficiency Patients on Regular Intravenous Immunoglobulin Treatment.

Pediatric allergy and immunology in Brazil.

Clinical manifestations and outcomes of pediatric chronic neutropenia.

Wan C, Yu HH, Lu MY, Lee JH, Wang LC, Lin YT, Yang YH, Chiang BL
J Formos Med Assoc 2012 Apr;111(4):220-7. Epub 2012 Mar 16 doi: 10.1016/j.jfma.2010.12.003. PMID: 22526211

Antibody responses to protein, polysaccharide, and phi X174 antigens in the hyperimmunoglobulinemia E (hyper-IgE) syndrome.

Sheerin KA, Buckley RH
J Allergy Clin Immunol 1991 Apr;87(4):803-11. doi: 10.1016/0091-6749(91)90126-9. PMID: 1826506

See all (8)

Prognosis

X-linked hyper-IgM syndrome with CD40LG mutation: two case reports and literature review in Taiwanese patients.

Tsai HY, Yu HH, Chien YH, Chu KH, Lau YL, Lee JH, Wang LC, Chiang BL, Yang YH
J Microbiol Immunol Infect 2015 Feb;48(1):113-8. Epub 2012 Sep 24 doi: 10.1016/j.jmii.2012.07.004. PMID: 23010537

Pediatric allergy and immunology in Brazil.

Study of patients with Hyper-IgM type IV phenotype who recovered spontaneously during late childhood and review of the literature.

Karaca NE, Durandy A, Gulez N, Aksu G, Kutukculer N
Eur J Pediatr 2011 Aug;170(8):1039-47. Epub 2011 Jan 28 doi: 10.1007/s00431-011-1400-2. PMID: 21274562

Molecular characterization of patients with X-linked Hyper-IgM syndrome: description of two novel CD40L mutations.

Rangel-Santos A, Wakim VL, Jacob CM, Pastorino AC, Cunha JM, Collanieri AC, Niemela JE, Grumach AS, Duarte AJ, Moraes-Vasconcelos D, Oliveira JB
Scand J Immunol 2009 Feb;69(2):169-73. doi: 10.1111/j.1365-3083.2008.02198.x. PMID: 19170966

Female hyper IgM syndrome type 1 with a chromosomal translocation disrupting CD40LG.

Imai K, Shimadzu M, Kubota T, Morio T, Matsunaga T, Park YD, Yoshioka A, Nonoyama S
Biochim Biophys Acta 2006 Mar;1762(3):335-40. Epub 2005 Oct 28 doi: 10.1016/j.bbadis.2005.10.003. PMID: 16311023

See all (15)

Clinical prediction guides

Clinical features and hematopoietic stem cell transplantations for CD40 ligand deficiency in Japan.

X-linked hyper-IgM syndrome with CD40LG mutation: two case reports and literature review in Taiwanese patients.

Tsai HY, Yu HH, Chien YH, Chu KH, Lau YL, Lee JH, Wang LC, Chiang BL, Yang YH
J Microbiol Immunol Infect 2015 Feb;48(1):113-8. Epub 2012 Sep 24 doi: 10.1016/j.jmii.2012.07.004. PMID: 23010537

Study of patients with Hyper-IgM type IV phenotype who recovered spontaneously during late childhood and review of the literature.

Karaca NE, Durandy A, Gulez N, Aksu G, Kutukculer N
Eur J Pediatr 2011 Aug;170(8):1039-47. Epub 2011 Jan 28 doi: 10.1007/s00431-011-1400-2. PMID: 21274562

Molecular characterization of patients with X-linked Hyper-IgM syndrome: description of two novel CD40L mutations.

Hyper-IgM syndrome type 4 with a B lymphocyte-intrinsic selective deficiency in Ig class-switch recombination.

Imai K, Catalan N, Plebani A, Maródi L, Sanal O, Kumaki S, Nagendran V, Wood P, Glastre C, Sarrot-Reynauld F, Hermine O, Forveille M, Revy P, Fischer A, Durandy A
J Clin Invest 2003 Jul;112(1):136-42. doi: 10.1172/JCI18161. PMID: 12840068 Free PMC Article

See all (11)

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Hyper-IgM syndrome type 4(HIGM4)

Definition

Clinical features

Term Hierarchy

Professional guidelines

PubMed

Recent clinical studies

Etiology

Diagnosis

Therapy

Prognosis

Clinical prediction guides

Supplemental Content

Table of contents

Genetic Testing Registry

Clinical resources

Practice guidelines

Molecular resources

Consumer resources

Reviews

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