Combined immunodeficiency develops with age in Immunodeficiency-centromeric instability-facial anomalies syndrome 2 (ICF2)

Orphanet J Rare Dis. 2014 Oct 21:9:116. doi: 10.1186/s13023-014-0116-6.


The autosomal recessive immunodeficiency-centromeric instability-facial anomalies syndrome (ICF) is characterized by immunodeficiency, developmental delay, and facial anomalies. ICF2, caused by biallelic ZBTB24 gene mutations, is acknowledged primarily as an isolated B-cell defect. Here, we extend the phenotype spectrum by describing, in particular, for the first time the development of a combined immune defect throughout the disease course as well as putative autoimmune phenomena such as granulomatous hepatitis and nephritis. We also demonstrate impaired cell-proliferation and increased cell death of immune and non-immune cells as well as data suggesting a chromosome separation defect in addition to the known chromosome condensation defect.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoimmune Diseases / diagnosis
  • Autoimmune Diseases / genetics
  • Centromere / genetics*
  • Child
  • Chromosomal Instability / genetics*
  • Chromosomes, Human / genetics
  • DNA Methylation
  • DNA Mutational Analysis
  • Disease Progression
  • Face / abnormalities*
  • Female
  • Humans
  • Immunologic Deficiency Syndromes / diagnosis*
  • Immunologic Deficiency Syndromes / genetics
  • Mutation
  • Phenotype
  • Primary Immunodeficiency Diseases
  • Repressor Proteins / genetics*


  • Repressor Proteins
  • ZBTB24 protein, human

Supplementary concepts

  • Combined Inflammatory and Immunologic Defect
  • Immunodeficiency syndrome, variable