Osteoporosis-pseudoglioma syndrome in four new patients: identification of two novel LRP5 variants and insights on patients’ management using bisphosphonates therapy

Summary This study describes the clinical, radiological, and molecular data of four new patients with osteoporosis-pseudoglioma syndrome and assesses their response to bisphosphonate therapy. Introduction Osteoporosis-pseudoglioma syndrome (OPPG) is a very rare disorder characterized mainly by severe juvenile osteoporosis and congenital blindness. OPPG is caused by biallelic mutations in the gene encoding low-density lipoprotein receptor-related protein 5 ( LRP5 ). Methods We present the clinical, radiological, and molecular findings of four new patients with OPPG from Egypt. We also assessed patients’ response to oral and intravenous bisphosphonate therapy. Results All patients had reduced bone mineral density (BMD) with variable number of fractures per year, in addition to bone abnormalities and the characteristic eye phenotype associated with OPPG. Mutation analyses of LRP5 gene revealed three different homozygous variants including two novel ones, c.7delG (p.A3Qfs*80) and c.3280G > A (p.E1094K). The c.3280G > A (p.E1094K) was recurrent in two unrelated patients who shared a unique haplotype suggesting a possible founder effect. The use of bisphosphonate therapy was beneficial; however, intravenous bisphosphonate administration led to a more favorable response. Conclusion Our study described the phenotypic and genetic features of four patients with OPPG and identified two new LRP5 variants, thus expanding the mutational spectrum of OPPG. In addition, our study reinforces the efficiency of using intravenous bisphosphonates in the management of patients with OPPG.