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Osteoporosis-pseudoglioma syndrome: clinical, genetic, and treatment-response study of 10 new cases in Greece

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Abstract

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.

Conclusion: The current study presents the molecular and clinical profiles of 10 new OPPG cases, being part of an extended pedigree. Patients who received bisphosphonate treatment responded well with increase in their BMD, though fractures occurred during therapy.

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.

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Abbreviations

aa:

amino acids

BMD:

bone mineral density

DXA:

dual-energy X-ray absorptiometry

FEVR:

familial exudative vitreoretinopathy

LRP5:

low-density lipoprotein receptor-related protein 5

OPPG:

osteoporosis-pseudoglioma syndrome

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Author information

Authors and Affiliations

  1. Third Department of Pediatrics, National and Kapodistrian University of Athens, “Attikon” University General Hospital, Athens, Greece

    Iordanis Papadopoulos, Evangelia Bountouvi, Achilleas Attilakos, Evangelia Gole, Argirios Dinopoulos, Polyxeni Nikolaidou & Anna Papadopoulou

  2. Second Department of Internal Medicine, Research Institute and Diabetes Center, National and Kapodistrian University of Athens, “Attikon” University General Hospital, Athens, Greece

    Melpomeni Peppa

Authors
  1. Iordanis Papadopoulos
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  2. Evangelia Bountouvi
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  3. Achilleas Attilakos
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  4. Evangelia Gole
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  5. Argirios Dinopoulos
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  6. Melpomeni Peppa
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  7. Polyxeni Nikolaidou
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  8. Anna Papadopoulou
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Contributions

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.

Corresponding author

Correspondence to Achilleas Attilakos.

Ethics declarations

The protocol was approved by the Institutional Review Board of the University Hospital “Attikon.”

Financial disclosure

The authors have no financial relationships relevant to this article.

Ethical approval

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.

Informed consent

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.

Additional information

Communicated by Peter de Winter

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Papadopoulos, I., Bountouvi, E., Attilakos, A. et al. Osteoporosis-pseudoglioma syndrome: clinical, genetic, and treatment-response study of 10 new cases in Greece. Eur J Pediatr 178, 323–329 (2019). https://doi.org/10.1007/s00431-018-3299-3

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  • DOI: https://doi.org/10.1007/s00431-018-3299-3

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