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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): Gene(s) directly associated with this condition or phenotype.	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.

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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.

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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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Decreased circulating IgA concentration

MedGen UID:: 57934
•Concept ID:: C0162538
•: Disease or Syndrome

Decreased levels of immunoglobulin A (IgA).

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Lymphadenopathy

MedGen UID:: 96929
•Concept ID:: C0497156
•: Disease or Syndrome

Enlargement (swelling) of a lymph node.

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Increased circulating IgM level

MedGen UID:: 333454
•Concept ID:: C1839972
•: Finding

An abnormally increased level of immunoglobulin M in blood.

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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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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.

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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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Abnormality of the digestive system
- Recurrent infection of the gastrointestinal tract
Abnormality of the immune system
Abnormality of the respiratory system
- Recurrent respiratory infections
- Recurrent upper and lower respiratory tract infections

Term Hierarchy

GTR
MeSH
Orphanet

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

CROGVHyper-IgM syndrome type 2

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 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

See all (1)

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: 36931691 Free 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: 33377626 Free 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: 27142677 Free PMC Article

See all (5)

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

See all (1)

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: 33377626 Free PMC Article

See all (1)

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: 35246784 Free 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: 33377626 Free PMC Article

Enrichment of rare variants in population isolates: single AICDA mutation responsible for hyper-IgM syndrome type 2 in Finland.

See all (3)

MedGen

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Hyper-IgM syndrome type 2(HIGM2)

Definition

Clinical features

Term Hierarchy

Professional guidelines

PubMed

Recent clinical studies

Diagnosis

Therapy

Prognosis

Clinical prediction guides

Supplemental Content

Table of contents

Genetic Testing Registry

Clinical resources

Practice guidelines

Molecular resources

Consumer resources

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