Clinical Phenotypes of Hyper-IgM Syndromes

M. Teresa de la Morena

Research output: Contribution to journalArticlepeer-review

62 Scopus citations


The primary immunodeficiency (PID) diseases comprise a heterogeneous group of inherited disorders of immune function. Technical advancements in whole-genome, whole-exome, and RNA-sequencing have seen the explosion of genetic discoveries in the field of PIDs. The present review aims to focus on a group of immunodeficiency disorders associated with elevated levels of IgM (hyper IgM; HIGM) and provides a clinical differential diagnosis. Most patients present for evaluation of immunodeficiency due to recurrent infections, and laboratory studies show either a clear isolated elevation of serum immunoglobulin M (IgM) with low or absent IgG, IgA, and IgE. Alternatively, IgM levels may be normal or moderately elevated while other serum immunoglobulins are reported below the norms for age but not absent. Mechanistically, these disorders are recognized as defects in immunoglobulin (Ig) class switch recombination (CSR). Importantly, to safeguard genetic stability, CSR utilizes elements of the DNA repair machinery including multi-protein complexes involved in mismatch repair (MMR). Therefore, it is not uncommon for defects in the DNA repair machinery, to present with laboratory findings of HIGM. This review will discuss clinical phenotypes associated with congenital defects associated with HIGM. Clinical manifestations, relevant immunologic testing, inheritance pattern, molecular diagnosis, presumed pathogenesis, and OMIM number, when annotated are compiled. Accepted therapeutic options, when available, are reviewed for each condition discussed.

Original languageEnglish (US)
Pages (from-to)1023-1036
Number of pages14
JournalJournal of Allergy and Clinical Immunology: In Practice
Issue number6
StatePublished - Nov 1 2016


  • Class switch recombination defects
  • HIGM
  • Hyper-IgM syndrome

ASJC Scopus subject areas

  • Immunology and Allergy


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