Barber–Say syndrome


Barber-Say syndrome is a very rare congenital disorder associated with excessive hair growth, fragile skin, eyelid deformities, and an overly broad mouth.
Barber-Say syndrome is phenotypically similar to Ablepharon macrostomia syndrome, which is also associated with dominant mutations in TWIST2.

Signs and symptoms

Multiple cases of parent-to-child transmission suggest that Barber-Say syndrome exhibits autosomal dominant inheritance. Exome sequencing and expression studies have shown that BSS is caused by mutations in the TWIST2 gene that affect a highly conserved residue of TWIST2. TWIST2 is a basic helix-loop-helix transcription factor that binds to E-box DNA motifs as a heterodimer and inhibits transcriptional activation. Because TWIST2 mediates mesenchymal stem cell differentiation and prevents premature or ectopic osteoblast differentiation, mutations in TWIST2 that disrupt these functions by altering DNA-binding activity could explain many of the phenotypes of BSS.

Epidemiology

The prevalence of Barber Say syndrome is less than 1 in 1,000,000. As of 2017, only 15 cases have been reported in the literature.