Osteoporosis-pseudoglioma syndrome: clinical, genetic, and treatment-response study of 10 new cases in Greece
Osteoporosis-pseudoglioma syndrome (OPPG) is a rare autosomal-recessive disorder, characterized by severe osteoporosis and early-onset blindness. Loss of function mutations in the gene encoding low-density lipoprotein receptor-related protein 5 (LRP5) have been established as the genetic defect of the disease. We report the clinical and genetic evaluation of ten OPPG cases in eight related nuclear families and their close relatives. Bone mineral density (BMD) in OPPG patients was assessed by dual-energy X-ray absorptiometry (DXA). Genotyping of LRP5 gene and targeted detection of index mutation were performed by DNA direct sequencing. Four patients were introduced to bisphosphonates. Mutational screening of LRP5 gene revealed the c.2409_2503+79del deletion in homozygous state, expected to result in a truncated protein. Among 44 members of the pedigree, 10 (22%) were identified homozygous and 34 (59%) heterozygous for this mutation. All patients had congenital blindness and 7 of them had also impaired bone mineral density. Four of them received bisphosphonates and responded with decreased bone pain and improvement in BMD; however, 3 patients presented with one fracture during treatment.
What is known:
• OPPG syndrome is a rare genetic disorder characterized by congenital blindness and juvenile osteoporosis.
• Loss of function mutations in the gene encoding low-density lipoprotein receptor-related protein 5 (LRP5) is the genetic defect of the disease.
What is new:
• Genetic and clinical phenotype of 10 new OPPG patients.
• The ten new OPPG patients presented with phenotypical variability in osseous manifestations.
KeywordsBisphosphonates Blindness LRP5 mutation OPPG Osteoporosis
bone mineral density
dual-energy X-ray absorptiometry
familial exudative vitreoretinopathy
low-density lipoprotein receptor-related protein 5
Iordanis Papadopoulos contributed to the acquisition of data and molecular analysis. Evangelia Bountouvi contributed to the analysis and interpretation of data and drafting of the manuscript. Dr. Anna Papadopoulou performed the molecular studies and contributed to the study design, interpretation of the results, and editing of the manuscript. Dr. Attilakos, Dr. Dinopoulos, and Dr. Nikolaidou contributed to the conception of the study and clinical evaluation of the patients and reviewed the manuscript. Dr. Gole contributed to the molecular analysis. Dr. Peppa performed the bone mineral density measurements.
Compliance with ethical standards
The protocol was approved by the Institutional Review Board of the University Hospital “Attikon.”
The authors have no financial relationships relevant to this article.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Written informed consent was obtained from the participants and the parents of the participating children.
Conflicts of interest
All the authors declare that they have no conflicts of interest.
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