Immunodeficiency-centromeric instability-facial anomalies syndrome

Immunodeficiency, centromeric instability and facial anomalies syndrome, usually called ICF syndrome, is a very rare inherited immune disorder passed on in an autosomal recessive way. It is marked by reduced levels of serum immunoglobulins (IgG, IgM and sometimes IgA), which leaves affected children open to repeated infections, and most patients die of infectious disease before adulthood. Typical facial features include widely spaced eyes, low-set ears, epicanthal folds and an enlarged tongue, and many patients also have intellectual disability and recurrent respiratory infections. Mutations in any of four genes, CDCA7, DNMT3B, HELLS and ZBTB24, can cause it. Diagnosis rests on karyotype, linkage or DNA sequence analysis and can be made before birth in families with a known history. The usual therapy is lifelong intravenous immunoglobulin, and stem cell transplantation has restored immune function in a small number of reported patients.