Immunodeficiency-centromeric instability-facial anomalies syndrome 1 (ICF1) is a rare immune disorder that has been reported in less than 50 patients worldwide. It is characterized by a variable reduction in immunoglobulin levels, mild dysmorphic facies including hypertelorism, micrognathia, flat face, low set ears, epicanthal folds and macroglossia, and heterochromatin abnormalities in chromosomes 1, 16 and 9 with increased somatic recombination and formation of multibranched configurations. Symptoms usually present in infancy or early childhood and include recurrent infections especially of the lower respiratory tract, failure to thrive and variable mental retardation.

Due to the variability in immunoglobulin levels, the mild nature of the dysmorphic features and the tendency to overlook cytogenetic findings, this syndrome is under-diagnosed in affected patients. It is treated by regular intravenous immunoglobulin infusions and antibiotics. However, due to the severity of the disorder, patients may succumb to secondary infections before reaching adulthood. 

ICF1 syndrome has been found to follow an autosomal recessive mode of inheritance. Defects in the DNMT3B gene, a DNA methyltransferase, have been linked to this disorder. More than 30 defects, mainly missense, nonsense and splicing mutations, as well as insertions and deletions, have so far been discovered in ICF1 affected patients either in the homozygous or compound heterozygous form.

It is important to note that in around 40% of ICF affected patients, no DNMT3B mutations are found. This may be due to the presence of a mutation in a transcriptional control element or another unknown gene.