Warsaw Breakage Syndrome – Definition
Warsaw Breakage Syndrome (OMIN #613398) is a hereditary syndromic disorder associated with increased chromosomal fragility and, thus, an increased risk of cancer. It is caused by a defect in the DDX11 gene, which is considered a tumor suppressor, among other things. The typical symptom triad is microcephaly, growth retardation, and deafness, which is often accompanied by cochlear malformations.
Synonym:
WABS
Gene:
DDX11 (ChlR1)
Gene product:
ATP-dependent DNA helicase DDX11
Function:
Sister chromatid cohesion and DNA replication, tumor suppressor
Pattern of inheritance:
Autosomal recessive
Prevalence:
Currently 23 cases described worldwide
Genotype-phenotype correlation:
Penetrance:
Unknown
Warsaw Breakage Syndrome – Diagnosis
Characteristic clinic in connection with the molecular genetic detection of a biallelic/homozygous pathogenic variant in the DDX11 gene.
- Analysis of the DDX11 gene
- DDX11 sequence analysis as a standard test
- In the absence of homozygous pathogenic variant detection, a targeted DDX11 deletion or duplication analysis is recommended.
- Multi-gene panel
In the absence of clinical or phenotypic evidence for WABS:
- Exome or genome sequencing
Differential Diagnoses
- Fanconi anemia
- Nijmegen breakage syndrome
- Roberts syndrome
- Microcephalic osteodysplastic primordial dwarfism type 2
Clinical Presentation
- Congenital microcephaly
- Pre- and postnatal growth retardation
- Cochlear hypoplasia with congenital deafness
- Intellectual disability and developmental delay
- Cardiovascular malformations
- Skeletal malformations (radial ray and thumb)
Individual abnormalities described:
- Pigmentary disorders of the skin
- Urogenital malformation
- Premature menarche
Cancer Predisposition
Due to the increased chromosomal fragility, an increased risk of cancer is assumed. However, due to the low prevalence, there are currently no precise estimates of the frequency and entity of cancers in the context of WABS.
Special Features of Treatment
- Optimization of the nutritional situation to promote sufficient growth and regular pediatrician checks of weight, height, head circumference, and BMI
- Cochlear implant with existing cochlear nerve
Diagnose Warsaw Breakage Syndrome. Wie geht es weiter?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Diagnosis of Warsaw Breakage Syndrome- What's Next?
Once diagnosed, it is recommended that a cancer predisposition specialist manage the patient. The following section explains whether cancer screening tests or other measures are necessary and how they should be performed. Some additional information, including links to support groups, is also included at the end of this page.
Recommendations for Early Detection in Your Patients
Due to the limited data available, no uniform, evidence-based screening recommendations exist.
- Regular clinical checks and, if necessary, further diagnostics in the event of abnormal findings
Warsaw Breakage Syndrome – Further Information
Additional Resources
Unfortunately, we are currently not aware of any support groups for patients with Warsaw Breakage syndrome. New information will be added as soon as it becomes available.
