Two Sisters with Congenital Blindness caused by Osteoporosis-pseudoglioma Syndrome due to new Mutations in the LPR5 Gene

Purpose To discover the reason behind two sisters being born blind with retinal detachment and microphthalmia with later findings of severe osteoporosis with low impact fractures. Methods Molecular testing identified biallelic lipoprotein receptor-related protein 5 (LRP5) mutations (NM_002335.3:c. [889dupA]; [2827 + 1G4A]) confirming a diagnosis of osteoporosis–pseudoglioma (OPPG) syndrome. Results Two new mutations in the LPR5 gene were each found in the unrelated parents of the girls and were found heterozygote in the girls. Both parents were then discovered to have osteopenia, as did several relatives, who all started preventive treatment. Conclusions OPPG is a autosomal recessive disease almost uniformly causing blindness from very early age with severe osteoporosis and low impact fractures, which was also the case of our two sisters. The diagnosis of OPPG was confirmed by sequencing the LPR5 gene, where two new mutations were found.