Genetic analysis combined with 3D-printing assistant surgery in diagnosis and treatment for an X-linked...

Hypophosphatemia is mainly characterized by hypophosphatemia and a low level of 1alpha,25-Dihydroxyvitamin D2 (1,25-(OH)₂ D2) and/or 1alpha,25-Dihydroxyvitamin D3 (1,25-(OH)₂ D3) in the blood. Previous studies have demonstrated that variants in PHEX and FGF23 are primarily responsible for this disease. Although patients with variants of these two genes share almost the same symptoms, they exhibit the different hereditary pattern, X-link dominant and autosome dominant, respectively. Three-dimensional (3D) printing is a method which can accurately reconstruct physical objects, and its applications in orthopedics can contribute to realizing a more accurate surgical performance and a better outcome.

An X-linked hypophosphatemia (XLH) family was recruited, with four patients across three generations. We screened candidate genes and filtered a duplication variant in PHEX. Variant analysis and co-segregation confirmation were then performed. Before the operation of our patient, a digital model of our patient's leg had been rebuilt upon the CT scan data, and a polylactic acid (PLA) model had been 3D-printed.

A novel duplication PHEX variant c.574dupG (p.A192GfsX20) was identified in a family with XLH. Its pathogenicity was confirmed by the co-segregation assay and online bioinformatics database. The preoperative plan was made with the help of the PLA model. Then, arch osteotomy and transverse osteotomy were performed under the guidance of the previous simulation. The appearance of the surgical-intervened leg was satisfactory.

This study identified a novel PHEX variant and showed that 3D printing tech is a very promising approach for corrective osteotomies.