2019 Sep 19;5(1):64. doi: 10.1038/s41572-019-0113-0.

Chromosome instability syndromes.

Author information

Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK. a.m.r.taylor@bham.ac.uk.
A-T Children's Project, Coconut Creek, FL, USA.
The University of Arizona Cancer Center, Tucson, AZ, USA.
Center for Chromosome Stability, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
Stem Cell and Leukaemia Proteomics Laboratory, and Paediatric and Adolescent Oncology, Institute of Cancer Sciences, University of Manchester, Manchester, UK.
Department of Paediatric and Adolescent Haematology and Oncology, Royal Manchester Children's Hospital and The Christie NHS Trust, Manchester, UK.
Department of Neurology and Pediatrics, Johns Hopkins University, Baltimore, MD, USA.
Laboratory of Genome Maintenance, Rockefeller University, New York, NY, USA.
Department of Immunology, The Children's Memorial Health Institute, Warsaw, Poland.
Department of Pediatrics (Pediatric Immunology), Amalia Children's Hospital, Radboud University Medical Center, Nijmegen, Netherlands.
Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK.


Fanconi anaemia (FA), ataxia telangiectasia (A-T), Nijmegen breakage syndrome (NBS) and Bloom syndrome (BS) are clinically distinct, chromosome instability (or breakage) disorders. Each disorder has its own pattern of chromosomal damage, with cells from these patients being hypersensitive to particular genotoxic drugs, indicating that the underlying defect in each case is likely to be different. In addition, each syndrome shows a predisposition to cancer. Study of the molecular and genetic basis of these disorders has revealed mechanisms of recognition and repair of DNA double-strand breaks, DNA interstrand crosslinks and DNA damage during DNA replication. Specialist clinics for each disorder have provided the concentration of expertise needed to tackle their characteristic clinical problems and improve outcomes. Although some treatments of the consequences of a disorder may be possible, for example, haematopoietic stem cell transplantation in FA and NBS, future early intervention to prevent complications of disease will depend on a greater understanding of the roles of the affected DNA repair pathways in development. An important realization has been the predisposition to cancer in carriers of some of these gene mutations.