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

J Clin Lab Anal. 2022 Mar;36(3):e24243. doi: 10.1002/jcla.24243.

PMID: 35106857

Jie-Yuan Jin, Li-Yang Zhang, Shuai Guo, Ke Tang

Highlights: This study identifies a novel PHEX variant and shows that 3D printing tech is a very promising approach for corrective osteotomies.

Abstract

Background: The primary characteristics of hypophosphatemia include hypophosphatemia and low blood levels of 1alpha,25-Dihydroxyvitamin D2 (1,25-(OH)2 D2) and/or 1alpha,25-Dihydroxyvitamin D3 (1,25-(OH)2 D3). Previous research has shown that the condition is predominantly caused by variations in the genes PHEX and FGF23. Despite having nearly identical symptoms, patients with variations of these two genes display divergent inheritance patterns, X-link dominant and autosome dominant, respectively. The use of three-dimensional (3D) printing in orthopedics can help achieve more precise surgical performance and a better result because this technique can accurately reproduce physical objects.

Methods: Four patients from a family with X-linked hypophosphatemia (XLH), spanning three generations, were enlisted. It was filtered a duplication variant in PHEX when screening potential genes. After that, co-segregation confirmation and variant analysis were carried out. Before the procedure on our patient, a polylactic acid (PLA) model and a digital reconstruction of the patient's leg from the CT scan data had been created.

Results: In a family with XLH, c.574dupG (p.A192GfsX20), a new duplication PHEX variant, was discovered. The co-segregation assay and an online bioinformatics database verified its pathogenicity. The PLA model was used to help create the preoperative plan. Then, with the aid of the earlier simulation, arch osteotomy and transverse osteotomy were carried out. The appearance of the surgical-intervened leg was satisfactory.

Conclusions: This work revealed a novel PHEX variant and demonstrated the great potential of 3D printing technology for corrective osteotomies.

Keywords: PHEX, FGF23, X-linked hypophosphatemia, three-dimensional printing, treatment