Immunodeficiency-centromeric instability facial anomalies (ICF) syndrome
Related genes: ZBTB24, DNMT3B, CDCA7, HELLS
Inheritance pattern: Autosomal recessive
Short for immunodeficiency-centromeric instability facial anomalies syndrome, ICF syndrome is an autosomal recessive disorder that may be due to variants in the ZBTB24, DNMT3B, CDCA7, or HELLS genes. Recurrent infections, mostly respiratory, are the usual presenting symptom, though it is also associated with mild facial dysmorphism, growth retardation, failure to thrive, and psychomotor retardation (the slowing down of thought and a reduction of physical movement). Although poor production of antibodies is most often described, some affected children also have severe cellular dysfunction, as evidenced by invasive fungal infection. T cell and B cell numbers and serum immunoglobulins are usually all low, and patients are susceptible to bacterial and opportunistic infections. Ig replacement therapy is the standard treatment. Hematopoietic stem cell transplantation (HSCT) has been curative for those with severe cellular dysfunction and may be considered in these cases.