Immunodeficiency with Centromere Instability and Facial Anomalies

Abstract Immunodeficiency with centromere instability and facial anomalies (ICF syndrome) (MIM 242860) is a rare autosomal recessive disease characterized by a variable immunodeficiency, mild facial anomalies, and chromosome instability involving the pericentromeric regions of chromosomes 1, 9, and 16. This disease was reported for the first time in the late 1970s by two groups independently (Hultén, 1978; Tiepolo et al., 1978, 1979). The patient described earlier by Østergaard (1973) also appears to have had ICF syndrome, based on the clinical symptoms and chromosomal abnormalities reported. The acronym ICF was suggested in accordance with the characteristic features of the syndrome: Immunodeficiency, Centromeric instability, and Facial anomalies (Maraschio et al., 1988). Only about 30 ICF patients have been described in the literature thus far, but underdiagnosis of the syndrome is quite possible because of phenotypic variability and infrequent chromosome analysis. Here we summarize the common clinical features of this limited set of patients as well as the molecular defects associated with ICF.