ABSTRACT
Variants in the COL1A1 gene typically lead to a connective tissue disorder called osteogenesis imperfecta (OI), which is characterized by increased bone fragility that may be associated with blue sclera, dentinogenesis imperfecta and hearing loss. However, the coexistence of pes equinovarus and OI is rare, and to date, no genetic basis has been described. We report a female patient who was admitted with short stature, and growth hormone replacement treatment was initiated following a diagnosis of growth hormone deficiency. She also had blue sclera, a bulbous nose, flexion contractures in both knee joints, tightness of Achilles tendons and hamstrings and bilateral pes planovarus. In infancy casting had also been applied due to bilateral pes equinovarus and she had experienced one bone fracture. Whole exome sequencing revealed a heterozygous pathogenic variant (c.2956G>A) in the COL1A1 gene. Pathogenic variants in the COL1A1 gene have been associated with OI. This rare variant of the COL1A1 gene should be considered in cases presenting with both pes equinovarus and joint contractures, particularly when accompanied by signs of increased bone fragility.
What is already known on this topic?
Pathogenic variants in the COL1A1 gene are most commonly associated with osteogenesis imperfecta. However, these pathogenic variants can lead to a wide range of clinical manifestations.
What this study adds?
The identified variant has been reported in only one father-son pair. Increased bone fragility, blue sclera, and short stature along with the presence of pes equinovarus and joint contractures in all three cases carrying this variant, have been considered noteworthy.
