LIG4 syndrome

LIG4 syndrome, or ligase IV syndrome, is an extremely rare condition caused by mutations in the gene for DNA ligase IV, an enzyme central to the non-homologous end joining pathway that repairs double-strand breaks in DNA and is needed to build T and B cell receptors. Severity depends on how far enzyme activity or gene expression is reduced. Some patients have a severe immunodeficiency with pancytopenia, leading to chronic respiratory infections and sinusitis, along with microcephaly, Seckel syndrome-like facial features, growth retardation and skin problems such as photosensitivity, psoriasis and telangiectasia. Hypothyroidism, type II diabetes and cancers such as acute T-cell leukemia may occur, and the picture closely resembles Nijmegen breakage syndrome.