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BTI - GeneReviews#. Nijmegen breakage syndrome (NBS) is characterized by progressive microcephaly, intrauterine growth retardation and short stature, recurrent sinopulmonary infections, an increased risk for cancer, and premature ovarian failure in females. Developmental milestones are attained at the usual time during the first year; however, borderline delays in development and hyperactivity may be observed in early childhood. Intellectual abilities tend to decline over time and most children tested after age seven years have mild to moderate intellectual disability. Recurrent pneumonia and bronchitis may result in respiratory failureand early death. About 35% of those reported have developed malignancies betweenages one and 34 years, with the risk being highest for B-cell lymphomas. Other tumors include T-cell lymphoma and solid tumors, such as medulloblastoma, glioma, and rhabdomyosarcoma. Note, however, that much of what is reported about NBS is based on individuals who are homozygous for the single most common Eastern European mutation, 657_661del5. Diagnosis is based on molecular genetic testing of NBS1, the only gene known to be associated with Nijmegen breakage syndrome. disease-causing mutations are identified in almost 100% of affected individuals.If the diagnosis is not established by molecular genetic testing, immunoblottingto determine if the nibrin protein is absent and colony survival assay to determine radiosensitivity can be used for diagnosis. Treatment of manifestations: Use of IVIg should be considered in individuals with severe humoral immunodeficiency and frequent infections. Surveillance: Periodic follow-up to monitor mental and physical growth and infection frequency. Monitoring for premature ovarian insufficiency should be considered in females. Agents/circumstances to avoid: Because the cells from individuals with NBS are radiosensitive in vitro, doses of radiation used in radiotherapy need to be reduced. NBS is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal testing are possible if both disease-causing alleles of an affected family member have been identified.#CI- Copyright (c) 1993-2013, University of Washington, Seattle. ALL rights reserved.#FED - Pagon, Roberta A#ED- Pagon RA#FED - Adam, Margaret P#ED- Adam MP#FED - Bird, Thomas D#ED- Bird TD#FED - Dolan, Cynthia R#ED- Dolan CR#FED - Fong, Chin-To#ED- Fong CT#FED - Stephens, Karen#ED- Stephens K#FAU - Concannon, Patrick