Congenital Bilateral Retinal Detachment in Two Siblings with Osteoporosis-Pseudoglioma Syndrome

The birth of a bilaterally blind child is catastrophic for families and a challenging diagnostic and management problem for ophthalmologists. Early identification of the underlying cause and its genetic basis helps initiate possible treatment, delineate prognosis, and identify risks for future pregnancies. In some cases, an early diagnosis can also influence the treatment of other family members. We report two sisters with bilateral retinal detachment and retro-lental masses from birth with no detectable NDP or FZD4 mutations. They were born to parents without detectable retinal anomalies. At 1 year of age, the elder sister had low impact bone fractures, and further evaluation identified severe osteopenia and multiple spinal compression fractures. Molecular testing identified biallelic lipoprotein receptor-related protein 5 (LRP5) mutations (NM-002335.3:c. [889dupA]; [2827 + 1G > A]) confirming a diagnosis of osteoporosis-pseudoglioma (OPPG) syndrome. After this diagnosis, the father and mother were found to have low bone mass and the father started on therapy. We conclude that early detection of LRP5 mutations is important for initiation of treatment of reduced bone density in the patients and their carrier relatives.