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Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

Warsaw breakage syndrome

Reviewed February 2014

What is Warsaw breakage syndrome?

Warsaw breakage syndrome is a condition that can cause multiple abnormalities. People with Warsaw breakage syndrome have intellectual disability that varies from mild to severe. They also have impaired growth from birth leading to short stature and a small head size (microcephaly). Affected individuals have distinctive facial features that may include a small forehead, a short nose, a small lower jaw, a flat area between the nose and mouth (philtrum), and prominent cheeks. Other common features include hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss) and heart malformations.

How common is Warsaw breakage syndrome?

Warsaw breakage syndrome is a rare condition; at least four cases have been described in the medical literature.

What genes are related to Warsaw breakage syndrome?

Mutations in the DDX11 gene cause Warsaw breakage syndrome. The DDX11 gene provides instructions for making an enzyme called ChlR1. This enzyme functions as a helicase. Helicases are enzymes that attach (bind) to DNA and temporarily unwind the two spiral strands (double helix) of the DNA molecule. This unwinding is necessary for copying (replicating) DNA in preparation for cell division, and for repairing damaged DNA and any mistakes that are made when DNA is copied. In addition, after DNA is copied, ChlR1 plays a role in ensuring proper separation of each chromosome during cell division. By helping repair mistakes in DNA and ensuring proper DNA replication, the ChlR1 enzyme is involved in maintaining the stability of a cell's genetic information.

DDX11 gene mutations severely reduce or completely eliminate ChlR1 enzyme activity. As a result, the enzyme cannot bind to DNA and cannot unwind the DNA strands to help with DNA replication and repair. A lack of functional ChlR1 impairs cell division and leads to an accumulation of DNA damage. This DNA damage can appear as breaks in the DNA, giving the condition its name. It is unclear how these problems in DNA maintenance lead to the specific abnormalities characteristic of Warsaw breakage syndrome.

Related Gene(s)

Changes in this gene are associated with Warsaw breakage syndrome.

  • DDX11

How do people inherit Warsaw breakage syndrome?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of Warsaw breakage syndrome?

These resources address the diagnosis or management of Warsaw breakage syndrome and may include treatment providers.

  • Centers for Disease Control and Prevention: Hearing Loss in Children (http://www.cdc.gov/ncbddd/hearingloss/index.html)
  • Genetic Testing Registry: Warsaw breakage syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C3150658)
  • MedlinePlus Encyclopedia: Hearing Loss--Infants (http://www.nlm.nih.gov/medlineplus/ency/article/007322.htm)

You might also find information on the diagnosis or management of Warsaw breakage syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/warsaw-breakage-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/warsaw-breakage-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Warsaw breakage syndrome?

You may find the following resources about Warsaw breakage syndrome helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Warsaw breakage syndrome?

  • WABS

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Warsaw breakage syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Warsaw breakage syndrome?

autosomal ; autosomal recessive ; cell ; cell division ; chromosome ; disability ; DNA ; DNA damage ; DNA replication ; double helix ; enzyme ; gene ; helicase ; inherited ; lower jaw ; microcephaly ; molecule ; philtrum ; recessive ; sensorineural ; sensorineural hearing loss ; short stature ; stature ; syndrome

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Capo-Chichi JM, Bharti SK, Sommers JA, Yammine T, Chouery E, Patry L, Rouleau GA, Samuels ME, Hamdan FF, Michaud JL, Brosh RM Jr, Mégarbane A, Kibar Z. Identification and biochemical characterization of a novel mutation in DDX11 causing Warsaw breakage syndrome. Hum Mutat. 2013 Jan;34(1):103-7. doi: 10.1002/humu.22226. Epub 2012 Oct 17. (http://www.ncbi.nlm.nih.gov/pubmed/23033317?dopt=Abstract)
  • van der Lelij P, Chrzanowska KH, Godthelp BC, Rooimans MA, Oostra AB, Stumm M, Zdzienicka MZ, Joenje H, de Winter JP. Warsaw breakage syndrome, a cohesinopathy associated with mutations in the XPD helicase family member DDX11/ChlR1. Am J Hum Genet. 2010 Feb 12;86(2):262-6. doi: 10.1016/j.ajhg.2010.01.008. Epub 2010 Feb 4. (http://www.ncbi.nlm.nih.gov/pubmed/20137776?dopt=Abstract)
  • van der Lelij P, Oostra AB, Rooimans MA, Joenje H, de Winter JP. Diagnostic Overlap between Fanconi Anemia and the Cohesinopathies: Roberts Syndrome and Warsaw Breakage Syndrome. Anemia. 2010;2010:565268. doi: 10.1155/2010/565268. Epub 2010 Jul 18. (http://www.ncbi.nlm.nih.gov/pubmed/21490908?dopt=Abstract)
  • Wu Y, Sommers JA, Khan I, de Winter JP, Brosh RM Jr. Biochemical characterization of Warsaw breakage syndrome helicase. J Biol Chem. 2012 Jan 6;287(2):1007-21. doi: 10.1074/jbc.M111.276022. Epub 2011 Nov 18. (http://www.ncbi.nlm.nih.gov/pubmed/22102414?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: February 2014
Published: July 28, 2014