Clinical, Immunologic and Molecular Spectrum of Patients with Immunodeficiency, Centromeric Instability, and Facial Anomalies (ICF) Syndrome: A Systematic Review

Endocr Metab Immune Disord Drug Targets. 2021;21(4):664-672. doi: 10.2174/1871530320666200613204426.

Abstract

Background: Immunodeficiency, centromeric instability and facial dysmorphism (ICF) syndrome is a rare autosomal recessive immune disorder presenting with hypogammaglobulinemia, developmental delay, and facial anomalies. The ICF type 1, type 2, type 3 and type 4 are characterized by mutations in DNMT3B, ZBTB24, CDCA7 or HELLS gene, respectively. This study aimed to present a comprehensive description of the clinical, immunologic and genetic features of patients with ICF syndrome.

Methods: PubMed, Web of Science, and Scopus were searched systemically to find eligible studies.

Results: Forty-eight studies with 118 ICF patients who met the inclusion criteria were included in our study. Among these patients, 60% reported with ICF-1, 30% with ICF-2, 4% with ICF-3, and 6% with ICF-4. The four most common symptoms reported in patients with ICF syndrome were: delay in motor development, low birth weight, chronic infections, and diarrhea. Intellectual disability and preterm birth among patients with ICF-2 and failure to thrive, sepsis and fungal infections among patients with ICF-1 were also more frequent. Moreover, the median levels of all three immunoglobulins (IgA, IgG, IgM) were markedly reduced within four types of ICF syndrome.

Conclusion: The frequency of diagnosed patients with ICF syndrome has increased. Early diagnosis of ICF is important since immunoglobulin supplementation or allogeneic stem cell transplantation can improve the disease-free survival rate.

Keywords: CDCA7; DNMT3B; HELLS; ICF syndrome; Immunodeficiency; ZBTB24; centromeric instability; facial dysmorphism syndrome; primary immunodeficiency.

Publication types

  • Systematic Review

MeSH terms

  • Agammaglobulinemia / diagnosis
  • Agammaglobulinemia / genetics
  • Agammaglobulinemia / immunology
  • Centromere / genetics*
  • Centromere / immunology*
  • Craniofacial Abnormalities / diagnosis
  • Craniofacial Abnormalities / genetics
  • Craniofacial Abnormalities / immunology
  • Face / abnormalities*
  • Humans
  • Mutation / genetics
  • Primary Immunodeficiency Diseases / diagnosis
  • Primary Immunodeficiency Diseases / genetics*
  • Primary Immunodeficiency Diseases / immunology*

Supplementary concepts

  • Immunodeficiency syndrome, variable