Nijmegen syndrome ... (Nijmegen breakage syndrome) - Gen NBN.  

Nijmegen syndrome is a disorder characterized by short stature, microcephaly, distinctive facial features, recurrent respiratory tract infections, increased risk of cancer, mental retardation and other health problems.

Generally, people with this condition grow slowly during infancy and early childhood. After this period of slow growth, people affected grow at a normal rate, but are still lower than normal. In most of those affected, progressive microcephaly is evident from birth. People with Nijmegen syndrome have distinctive facial features including a sloping forehead, a prominent nose, large ears, small jaw, and oblique palpebral fissures up. These facial features usually become evident at 3 years.

Additionally, affected individuals have immunodeficiency with abnormally low levels of immunoglobulin G (IgG) and immunoglobulin A (IgA). Affected individuals also have a shortage of T cell immune system abnormalities increase susceptibility to recurrent, such as bronchitis, pneumonia, sinusitis and other infections which affect the upper respiratory tract and lung infections. In addition, affected individuals are at increased risk of developing cancer, usually Hodgkin's lymphoma. Other cancers seen in people with Nijmegen syndrome include brain tumors, medulloblastoma and glioma like, and rhabdomyosarcoma muscle tissue. People with Nijmegen syndrome are 50 times more likely to develop cancer than people without this condition. Intellectual development is normal in most people with this condition during the first second year of life, but then becomes delayed development. Affected women often have premature ovarian failure, primary amenorrhea or infrequent menstrual periods. Most affected women are sterile.

This process is due to mutations in the NBN gene, located on the long arm of chromosome 8 (8q21), encoding the protein nibrin, involved in several critical cellular functions, including DNA damage repair. Also it interacts with two other proteins, encoded from the MRE11A and RAD50 genes, as part of a larger complex works to repair DNA strand breaks. This interaction helps to maintain the stability of the genetic information of a cell through its functions in the repair of damaged DNA and the regulation of cell division.

They have identified at least 10 mutations in the gene that cause NBN Nijmegen syndrome. The most frequent mutation eliminates five nucleotides of the gene (657_661del5). This mutation leads to the synthesis of a shortened version of the protein called p70-nibrin nibrin. The defective protein causes repair damaged DNA is not properly performed. As a result, the accumulation of errors in DNA can trigger the cells grow and divide abnormally, increasing the risk of cancer. A decrease in the number of immune cells produced, leads to reduced amounts of immunoglobulins and other features immunodeficiency.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with Nijmegen syndrome by complete PCR amplification of exons NBN gene, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).