Immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome is an IEI typically characterized by recurrent infections, chromosomal abnormalities, and facial dysmorphism as the result of pathogenic variants in DNA methylation genes such as DNMT3B (ICF1) [4], ZBTB24 (ICF2) [5], CDCA7 (ICF3) [6], and HELLS (ICF4) [6]. The gene discussed is HELLS; the disease is infection.