Early-onset primary antibody deficiency resembling common variable immunodeficiency challenges the diagnosis of Wiedeman-Steiner and Roifman syndromes

Sci Rep. 2017 Jun 16;7(1):3702. doi: 10.1038/s41598-017-02434-4.


Syndromic primary immunodeficiencies are rare genetic disorders that affect both the immune system and other organ systems. More often, the immune defect is not the major clinical problem and is sometimes only recognized after a diagnosis has been made based on extra-immunological abnormalities. Here, we report two sibling pairs with syndromic primary immunodeficiencies that exceptionally presented with a phenotype resembling early-onset common variable immunodeficiency, while extra-immunological characteristics were not apparent at that time. Additional features not typically associated with common variable immunodeficiency were diagnosed only later, including skeletal and organ anomalies and mild facial dysmorphism. Whole exome sequencing revealed KMT2A-associated Wiedemann-Steiner syndrome in one sibling pair and their mother. In the other sibling pair, targeted testing of the known disease gene for Roifman syndrome (RNU4ATAC) provided a definite diagnosis. With this study, we underline the importance of an early-stage and thorough genetic assessment in paediatric patients with a common variable immunodeficiency phenotype, to establish a conclusive diagnosis and guide patient management. In addition, this study extends the mutational and immunophenotypical spectrum of Wiedemann-Steiner and Roifman syndromes and highlights potential directions for future pathophysiological research.

Publication types

  • Case Reports
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinemia / diagnosis*
  • Agammaglobulinemia / immunology*
  • Age of Onset
  • Biomarkers
  • Cardiomyopathies / diagnosis*
  • Cardiomyopathies / immunology*
  • Common Variable Immunodeficiency / diagnosis*
  • Common Variable Immunodeficiency / immunology*
  • Cytogenetics
  • Diagnosis, Differential
  • Genome-Wide Association Study
  • Humans
  • Immunologic Deficiency Syndromes / diagnosis*
  • Immunologic Deficiency Syndromes / immunology*
  • Immunophenotyping
  • Infant, Newborn
  • Male
  • Mental Retardation, X-Linked / diagnosis*
  • Mental Retardation, X-Linked / immunology*
  • Osteochondrodysplasias / diagnosis*
  • Osteochondrodysplasias / immunology*
  • Pedigree
  • Phenotype
  • Primary Immunodeficiency Diseases
  • RNA, Small Nuclear / genetics
  • Retinal Diseases / diagnosis*
  • Retinal Diseases / immunology*
  • Sequence Analysis, DNA
  • Siblings


  • Biomarkers
  • RNA, Small Nuclear
  • RNU4ATAC RNA, human

Supplementary concepts

  • Roifman syndrome