COL9A1-related disorder with pectus carinatum, without epiphyseal dysplasia: case report and review of literature.

Abstract

COL9A1 encodes the alpha-1 chain of type IX collagen heterotrimer, which is a vital component of collagen fibrils in hyaline cartilage. There are preliminary lines of evidence suggesting that COL9A1 mutations may be associated with autosomal dominant multiple epiphyseal dysplasia (MED), a disorder affecting the epiphysis of long bones. With only 2 reported cases (both from the same family) of MED in autosomal dominant COL9A1-related disorders (MIM 614135) in the clinical scientific literature hitherto, the phenotype is poorly understood at present. Here, we report the clinical and imaging findings associated with a novel COL9A1 mutation in comparison to the previously reported cases. We studied a 22-year-old male, who presented with a chronic history of leg pain and laxity of the knee joint, in the context of a history of pectus carinatum requiring a chest brace, and tall stature (height = 186.9cm) with bilateral piezogenic pedal papules. Gene panel testing and a radiographic skeletal survey were subsequently performed. Gene panel test showed a heterozygous pathogenic variant in the COL9A1 that is denoted as c.188del (p.Phe63Serfs*3) and is predicted to result in a loss-of-function. The patient's long bones all appeared slender on a radiograph, without apparent epiphyseal dysplasia. Our findings suggest that the phenotypic spectrum of COL9A1-related disorders may potentially include other skeletal anomalies (such as pectus carinatum and slender appearance of long bones) aside from epiphyseal dysplasia.