Co-occurrence of Spondyloepiphyseal Dysplasia and X-Linked Hypophosphatemia in a Three-Generation Chinese Family

This study aims to share the diagnostic experience on a three-generation Chinese family with co-occurrence of spondyloepiphyseal dysplasia (SED) and X-linked hypophosphatemia (XLH), and evaluate the therapeutic effects of two third-generation siblings. The proband, his younger brother, and mother presented with short stature, skeletal problems, and hypophosphatemia. His father, paternal grandfather, and aunt also manifested short stature and skeletal deformities. Whole exome sequencing (WES) of proband –brother–parents initially only found the proband and his younger brother had a pathogenic c.2833G >  A(p.G945S) variant in theCOL2A1 gene inherited from their father. Re-analysis of WES uncovered the proband and his younger brother also harbored a pathogenic ex.12 del variant in thePHEX gene transmitted from their mother. Sanger sequencing, agarose gel electrophoresis, and quantitative polymerase chain reaction proved these results. The proband and his younger brother were confirmed to have a paternally inherited SED and a maternally inherited XLH. During a 2.8-year follow-up, these two siblings remained short stature and hypophosphatemia, but their radiographic signs and serum bone alkaline phosphatase levels were improved with treatment of oral phosphate and calcitriol. Our study presents the first report of co-occurrence of SED and XLH, shows the possibility that two different rare GSDs co-exist in a single patient, and alerts clinicians and geneticists to be cauti...
Source: Calcified Tissue International - Category: Orthopaedics Source Type: research