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

Severe hypertrichosis, especially of the back
Skin abnormalities, including hyperlaxity and redundancy
Facial dysmorphism, including macrostomia
Eyelid deformities
Abnormal and low-set ears
Bulbous nasal tip with hypoplastic alae nasi
Low frontal hairline

Genetics

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.