LIG4 syndrome is a hereditary disorder associated with impaired DNA double-strand break repair mechanisms and characterized by microcephaly, unusual facial features, growth and developmental delay, skin anomalies, and pancytopenia, which is associated with combined immunodeficiency (CID).
Prevalence is unknown. To date, at least 12 patients have been reported.
LIG4 syndrome presents in childhood with microcephaly, unusual facial features that have been described as ''bird-like'' (beak-like nose and micrognathia), growth and developmental delay, skin anomalies including photosensitivity and psoriatic-like lesions, and pancytopenia. The disease is associated with immunodeficiency. Some patients have been reported as having telangiectasias, leukemia, lymphoma, bone marrow abnormalities, and type 2 diabetes. One patient presented with features of Omenn syndrome (see this term).
LIG4 syndrome is caused by mutations in the LIG4 gene (13q22-q34). The resulting defect of DNA ligase IV, a component of the classical non-homologous end-joining (NHEJ) pathway, affects the major mechanism of DNA double-strand break repair.
Diagnosis is based on evidence of the characteristic clinical signs of LIG4 syndrome, particularly the ''bird-like'' facial features, and low T and B cells. Diagnosis is confirmed on the basis of molecular genetic analysis and the evidence of radiosensitivity of cell lines. Chromosome 7/14 translocations are also common.
Differential diagnoses include other rare DNA damage response diseases such as Seckel syndrome, Nijmegen breakage syndrome (NBS), Cernunnos-XLF deficiency and Fanconi anemia (see these terms).
Prenatal diagnosis can be performed by chorionic villus sampling in families with previously affected members.
Transmission is autosomal recessive.
Supportive treatment is with prophylactic antibiotics and anti-virals. Hematopoietic stem cell transplantation may be indicated in some patients using modified conditioning regimens without radiotherapy.
Lifespan is generally limited with an increased incidence of leukemia or lymphoma.
Last update: July 2012