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Hyper-IgM syndrome type 2(HIGM2)

MedGen UID:
354548
•Concept ID:
C1720956
•
Disease or Syndrome
Synonyms: Hyper-IgM Immunodeficiency Syndrome, Type 2; Immunodeficiency with hyper IgM type 2
 
Gene (location): AICDA (12p13.31)
 
Monarch Initiative: MONDO:0011528
OMIM®: 605258
Orphanet: ORPHA101089

Definition

Hyper-IgM syndrome type 2 (HIGM2) is a rare immunodeficiency characterized by normal or elevated serum IgM levels with absence of IgG, IgA, and IgE, resulting in a profound susceptibility to bacterial infections. For a discussion of genetic heterogeneity of immunodeficiency with hyper-IgM, see HIGM1 (308230). [from OMIM]

Clinical features

From HPO
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
Recurrent upper and lower respiratory tract infections
MedGen UID:
375014
•Concept ID:
C1842777
•
Finding
Increased susceptibility to upper and lower respiratory tract infections, as manifested by recurrent episodes of upper and lower respiratory tract infections.
See: Feature record | Search on this feature
Recurrent respiratory infections
MedGen UID:
812812
•Concept ID:
C3806482
•
Finding
An increased susceptibility to respiratory infections as manifested by a history of recurrent respiratory infections.
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
Decreased circulating IgA concentration
MedGen UID:
57934
•Concept ID:
C0162538
•
Disease or Syndrome
Decreased levels of immunoglobulin A (IgA).
See: Feature record | Search on this feature
Lymphadenopathy
MedGen UID:
96929
•Concept ID:
C0497156
•
Disease or Syndrome
Enlargement (swelling) of a lymph node.
See: Feature record | Search on this feature
Increased circulating IgM level
MedGen UID:
333454
•Concept ID:
C1839972
•
Finding
An abnormally increased level of immunoglobulin M in blood.
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
Complete or near-complete absence of specific antibody response to tetanus vaccine
MedGen UID:
1687415
•Concept ID:
C5139458
•
Finding
The inability to synthesize postvaccination antibodies against a tetanus antigen, as measured by antibody titer determination following vaccination.
See: Feature record | Search on this feature
Decreased circulating IgG concentration
MedGen UID:
1720114
•Concept ID:
C5234937
•
Finding
An abnormally decreased level of immunoglobulin G (IgG) in blood.
See: Feature record | Search on this feature
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Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHyper-IgM syndrome type 2
Follow this link to review classifications for Hyper-IgM syndrome type 2 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

Diagnosis

Type 2 hyper-IgM syndrome with a rare variant of AICDA gene mutation in a young woman.
Prakash PR, Gupta G, Aggarwal M, Baitha U
BMJ Case Rep 2023 Mar 17;16(3) doi: 10.1136/bcr-2022-253878. PMID: 36931691Free PMC Article
Novel mutations in hyper-IgM syndrome type 2 and X-linked agammaglobulinemia detected in three patients with primary immunodeficiency disease.
Chen X, Liu F, Yuan L, Zhang M, Chen K, Wu Y
Mol Genet Genomic Med 2021 Jan;9(1):e1552. Epub 2020 Dec 30 doi: 10.1002/mgg3.1552. PMID: 33377626Free PMC Article
Hyper IgM Syndrome Type 2 Presenting as Intestinal Lymphoid Polyposis Without Recurrent Infection.
de la Varga-Martínez R, Vilches-Moreno M, Viejo-Almanzor A, Pérez-Requena J, Rodríguez C, Mora-López F
J Investig Allergol Clin Immunol 2020;30(5):362-364. Epub 2020 Jul 21 doi: 10.18176/jiaci.0504. PMID: 32694097
A Severe Anaphylactic Reaction Associated with IgM-Class Anti-Human IgG Antibodies in a Hyper-IgM Syndrome Type 2 Patient.
Tsujita Y, Imai K, Honma K, Kamae C, Horiuchi T, Nonoyama S
J Clin Immunol 2018 Jan;38(1):144-148. Epub 2017 Dec 19 doi: 10.1007/s10875-017-0466-7. PMID: 29255996
Enrichment of rare variants in population isolates: single AICDA mutation responsible for hyper-IgM syndrome type 2 in Finland.
Trotta L, Hautala T, Hämäläinen S, Syrjänen J, Viskari H, Almusa H, Lepisto M, Kaustio M, Porkka K, Palotie A, Seppänen M, Saarela J
Eur J Hum Genet 2016 Oct;24(10):1473-8. Epub 2016 May 4 doi: 10.1038/ejhg.2016.37. PMID: 27142677Free PMC Article

Therapy

A Severe Anaphylactic Reaction Associated with IgM-Class Anti-Human IgG Antibodies in a Hyper-IgM Syndrome Type 2 Patient.
Tsujita Y, Imai K, Honma K, Kamae C, Horiuchi T, Nonoyama S
J Clin Immunol 2018 Jan;38(1):144-148. Epub 2017 Dec 19 doi: 10.1007/s10875-017-0466-7. PMID: 29255996

Prognosis

Novel mutations in hyper-IgM syndrome type 2 and X-linked agammaglobulinemia detected in three patients with primary immunodeficiency disease.
Chen X, Liu F, Yuan L, Zhang M, Chen K, Wu Y
Mol Genet Genomic Med 2021 Jan;9(1):e1552. Epub 2020 Dec 30 doi: 10.1002/mgg3.1552. PMID: 33377626Free PMC Article

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
Novel mutations in hyper-IgM syndrome type 2 and X-linked agammaglobulinemia detected in three patients with primary immunodeficiency disease.
Chen X, Liu F, Yuan L, Zhang M, Chen K, Wu Y
Mol Genet Genomic Med 2021 Jan;9(1):e1552. Epub 2020 Dec 30 doi: 10.1002/mgg3.1552. PMID: 33377626Free PMC Article
Enrichment of rare variants in population isolates: single AICDA mutation responsible for hyper-IgM syndrome type 2 in Finland.
Trotta L, Hautala T, Hämäläinen S, Syrjänen J, Viskari H, Almusa H, Lepisto M, Kaustio M, Porkka K, Palotie A, Seppänen M, Saarela J
Eur J Hum Genet 2016 Oct;24(10):1473-8. Epub 2016 May 4 doi: 10.1038/ejhg.2016.37. PMID: 27142677Free PMC Article

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