Bisphosphonate treatment at spondylo‐ocular syndrome due to a novel compound heterozygote variant in XYLT2 and review of the literature

Abstract

Spondylo‐ocular syndrome is a rare autosomal recessive disorder characterized by generalized osteoporosis, hearing loss, visual impairment due to cataract, and platyspondyly. Previous studies have revealed that the syndrome is caused by pathogenic variants in the XYLT2 gene. A patient with spondylo‐ocular syndrome and two heterozygous pathogenic variant in the XYLT2 gene in compound state are described here. The patient presented with osteoporosis, platyspondyly, ocular findings, hearing loss, kyphosis, scoliosis, facial findings, intellectual disability, and undescended testicles. Previous reports of bisphosphonate treatment response were variable, whereas a long‐term follow‐up with bisphosphonate treatment in this case resulted in normalization of vertebral structures. Reporting such cases helps to determine the appropriate genotype–phenotype correlation in patients with XYLT2‐related pathogenesis.

Xylosyltransferase-Deficiency in Human Dermal Fibroblasts Induces Compensatory Myofibroblast Differentiation and Long-Term ECM Reduction

“…Homozygous XYLT2 mutations lead to spondylo-ocular syndrome, which is associated with short stature, retinal detachment, amblyopia, nystagmus, hearing loss, heart valve defects, bone fragility and mild learning difficulties [ 18 , 19 , 20 , 21 ]. To date, 24 patients from 13 different families have been described harboring this syndrome [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Predominantly homozygous mutations lead to the clinical picture of spondylo-ocular syndrome, but the most recently discovered pathogenic mutations were compound heterozygous [ 23 ].…”

“…To date, 24 patients from 13 different families have been described harboring this syndrome [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 ]. Predominantly homozygous mutations lead to the clinical picture of spondylo-ocular syndrome, but the most recently discovered pathogenic mutations were compound heterozygous [ 23 ].…”