Mutations in COL27A1 cause a spectrum of autosomal recessive osteochondrodysplasias that share as main clinical features: short stature, bilateral hip dislocations, carpal coalitions and scoliosis. Other features can include oval-shaped skull with prominent forehead, cervical anomalies and bilateral hearing loss. The main disorder associated with mutation in COL27A1 is Steel Syndrome (STLS, MIM #615155), which was originally identified and described in patients of Puerto Rican ancestry. Steel syndrome is caused by homozygosity for the p.Gly697Arg variant in COL27A1, which is a founder mutation in Puerto Rico and surrounding islands in the Caribbean. A child with short stature, congenital bilateral hip dislocations and reported Puerto Rican ancestry is highly suspected to have a clinical and molecular diagnosis of Steel syndrome.
Since the identification of the molecular cause of Steel syndrome, additional patients with biallelic loss of function variants in COL27A1 and phenotypes in the spectrum of Steel syndrome but with more severe clinical manifestations have been reported.