Warsaw breakage syndrome

Warsaw breakage syndrome is a rare genetic condition. Fewer than 10 cases have been reported by 2018.

Its clinical manifestations affect several organ systems.

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.

Clinical features

These include

• 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

Differential diagnosis

• Bloom syndrome
• Cornelia de Lange syndrome
• Fanconi anemia
• Nijmegen breakage syndrome
• Roberts syndrome
• Xeroderma pigmentosum

Diagnosis

The diagnosis may be suspected on clinical grounds and can be confirmed by sequencing the DDX1 gene.

Treatment

There is no known curative treatment for this condition presently. Management is supportive.

History

This condition was first described in 2010. Portions of content adapted from Wikipedia's article on Warsaw breakage syndrome which is released under the CC BY-SA 3.0.