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.
Immunodeficiency, centromeric heterochromatin instability of chromosomes 1, 9, and 16, and facial anomalies: the ICF syndrome.
