Spectrum of LRP5-Related Bone Disease Within a Single Family: Osteoporosis-Pseudoglioma Syndrome in Two Siblings and Adult-Onset Osteoporosis in their Mother
DOI:
https://doi.org/10.60591/crspmi.536Keywords:
Low Density Lipoprotein Receptor-Related Protein-5, OsteoporosisAbstract
Mutations in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with a wide spectrum of bone phenotypes, ranging from severe osteoporosis-pseudoglioma syndrome (OPPG) to isolated early-onset osteoporosis. We describe a family with compound heterozygous LRP5 mutations causing OPPG in two siblings, characterized by congenital or progressive blindness, severe osteoporosis and recurrent fractures, and a heterozygous LRP5 mutation in their mother, presenting as adult-onset primary osteoporosis without ocular involvement. Bone mineral density was markedly reduced in all cases. Bisphosphonate therapy and calcium-vitamin D supplementation were initiated, with stabilization or modest improvement in bone density. This family illustrates the broad phenotypic variability of LRP5-related bone disease and highlights the importance of genetic evaluation in familial or unexplained osteoporosis. Recognition of LRP5 mutations enables accurate diagnosis, appropriate treatment and targeted family screening.
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Copyright (c) 2026 Christine Canizes Paiva, Tiago Jorge Costa, Odete Duarte, Joana Cascais Costa, Hélder Esperto
This work is licensed under a Creative Commons Attribution 4.0 International License.
