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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.
See: Feature record | Search on this feature
Recurrent infection of the gastrointestinal tract
MedGen UID:
343135
•Concept ID:
C1854495
•
Disease or Syndrome
Recurrent infection of the gastrointestinal tract.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
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).
See: Feature record | Search on this feature
Autoimmune hemolytic anemia
MedGen UID:
1918
•Concept ID:
C0002880
•
Disease or Syndrome
An autoimmune form of hemolytic anemia.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
Autoimmune thrombocytopenia
MedGen UID:
116621
•Concept ID:
C0242584
•
Disease or Syndrome
The presence of thrombocytopenia in combination with detection of antiplatelet antibodies.
See: Feature record | Search on this feature
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.
See: Feature record | Search on this feature
Recurrent bacterial infections
MedGen UID:
334943
•Concept ID:
C1844383
•
Finding
Increased susceptibility to bacterial infections, as manifested by recurrent episodes of bacterial infection.
See: Feature record | Search on this feature
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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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHyper-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

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

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: 30053428Free 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.
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

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.
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
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
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

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.
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
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

Clinical prediction guides

A Novel AICDA Splice-Site Mutation in Two Siblings with HIGM2 Permits Somatic Hypermutation but Abrogates Mutational Targeting.
Dirks J, Haase G, Cantaert T, Frey L, Klaas M, Rickert CH, Girschick H, Meffre E, Morbach H
J Clin Immunol 2022 May;42(4):771-782. Epub 2022 Mar 5 doi: 10.1007/s10875-022-01233-5. PMID: 35246784Free PMC Article
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
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
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: 12840068Free PMC Article

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