Warsaw breakage syndrome
| Warsaw breakage syndrome | |
|---|---|
| Other names | WABS[1] |
Warsaw breakage syndrome is a rare genetic condition. Fewer than 10 cases have been reported by 2018.[2]Its clinical manifestations affect several organ systems.
Presentation
These include[3]
- Severe pre- and postnatal growth retardation
- Microcephaly
- Intellectual disability
- Dysmorphic features
- Small and elongated face
- Narrow bifrontal diameter
- Prominent cheeks
- Small nares
- Flat philtrum
- Relatively large mouth
- Bilateral epicanthal folds
- High arched palate
- Microretrognathism
- Coloboma of the optic disc
- Strabismus
- Cup-shaped ears
- Sensorineural deafness
- Short neck
- Jugular hypoplasia
- Cardiac features
- Ventricular septal defect
- Tetralogy of Fallot
- Sketelal features
- Clinodactyly of the fifth fingers
- Syndactyly of the second and third toes
- Small thumbs
- Small fibulae
- Others
- Abnormal skin pigmentation
- Single palmar crease
Genetics
This condition is caused by mutations in the DDX11 gene which is located on the short arm of chromosome 12 (12p11).
This gene encodes an iron-sulfur containing DNA helicase that belongs to the superfamily 2 of helicases. This protein interacts with the 9-1-1 checkpoint complex protein.
The inheritance pattern is not yet clear.
Diagnosis
The diagnosis may be suspected on clinical grounds and can be confirmed by sequencing the DDX11 gene.
Differential diagnosis
- Bloom syndrome
- Cornelia de Lange syndrome
- Fanconi anemia
- Nijmegen breakage syndrome
- Roberts syndrome
- Xeroderma pigmentosum
Treatment
There is no known curative treatment for this condition presently. Management is supportive.
History
This condition was first described in 2010.[4]
References
- ^ "OMIM Entry - # 613398 - WARSAW BREAKAGE SYNDROME; WABS". omim.org. Retrieved 29 October 2019.
- ^ Alkhunaizi E, Shaheen R, Bharti SK, Joseph-George AM, Chong K, Abdel-Salam GMH, Alowain M, Blaser SI, Papsin BC, Butt M, Hashem M, Martin N, Godoy R, Brosh RM Jr, Alkuraya FS, Chitayat D (2018) Warsaw breakage syndrome: Further clinical and genetic delineation. Am J Med Genet A doi: 10.1002/ajmg.a.40482
- ^ Pisani FM (2019) Spotlight on Warsaw Breakage Syndrome. Appl Clin Genet 12:239-248
- ^ van der Lelij P, Chrzanowska KH, Godthelp BC, Rooimans MA, Oostra AB, Stumm M, Zdzienicka MZ, Joenje H, de Winter JP (2010) Warsaw breakage syndrome, a cohesinopathy associated with mutations in the XPD helicase family member DDX11/ChlR1. Am J Hum Genet 86(2):262-6. doi: 10.1016/j.ajhg.2010.01.008