Hyperimmunoglobulinemia IgM syndrome/other types

In addition to the most common X-linked form caused by a mutation in the gene for the CD40 ligand, there are several rare forms of IgM hyperglobulinemia. The underlying clinical signs (high IgM and no or low levels of of other Ig) are the same in all forms.

IgM hyperimmunoglobulinemia syndrome, type 2
(HIGM2, OMIM: 605258)

This form is caused by mutation of AICDA gene (Activation-induced cytidine deaminase, localization 12p13). Unlike the HIGM1 form, there is probably a defect in B-lymphoctes and patients are not prone to opportunistic infections. Heredity is autosomal recessive.

IgM hyperimmunoglobulinemia syndrome, type 3
(HIGM3, OMIM: 606843)

This form is caused by a mutation in the gene for the CD40 antigen (localization 20q12-q13.2). It is inherited as an autosomal recessive trait. The same process as in HIGM1 is disrupted, there is no isotype rearranging and similar clinical manifestations occur.

IgM hyperimmunoglobulinemia syndrome, type 4
(HIGM4, OMIM: 608184)

So far, we know the least about this form. The manifestations are similar to those of HIGM2 – but AICDA activity is maintained and the overall course is lighter (partial IgG production is preserved). It is likely to be a regulation disorder of isotype rearranging or defects in DNA reperative mechanisms.

IgM hyperimmunoglobulinemia syndrome, type 5
(HIGM5, OMIM: 608106)

This form is caused by mutation of the UNG gene (Uracil-DNA glycosylase, localization 12q23-q24.1). Here too we find a defect in the isotype rearrangement and a phenotype most corresponding to the HIGM2 form.