Osteoporosis-pseudoglioma syndrome
| Osteoporosis-pseudoglioma syndrome | |
|---|---|
 | |
| Specialty | Medical genetics |
Osteoporosis-pseudoglioma syndrome or OPGG is a rare genetic condition which is characterized by early-onset blindness and severe osteoporosis alongside seemingly random bone fractures.
Signs and symptoms
It is clinically characterized by severe osteoporosis which is usually recognized and posteriorly diagnosed in early childhood, this usually leads to various complications, with the main one being recurrent bone fractures.[1][2]
Another very common symptom is total blindness, it usually manifests in two ways:
- Severe congenital impairment of the vision which progresses into total blindness by adulthood
- Congenitally normal vision which rapidly progresses into severe visual impairment by early infancy and total blindness by adulthood
Occasional findings include epilepsy, intellectual disabilities, joint hypermobility, hypotonia,[1] cataracts, microphthalmia, and iris, lens, and vitreous defects.[3]
People with only one copy of the gene mutation involved in this condition (heterozygotes) are at a higher risk of developing exudative vitreoretinopathy and having low bone density, which can consequently result in osteoporosis.[4]
Complications
This condition, as it was mentioned before, is associated with various complications, most of which are osseous.[1]
They are the following:
- Recurrent bone fractures
- Bone fracture-associated compressed vertebrae
- Scoliosis
- Generalized limb abnormalities
- Craniotabes
- Short stature
Anatomy
Osteoporosis and the complications which are brought to light by it are caused by a decreased level of minerals within the bones.[1]
The visual impairments are caused by a group of ocular conditions known as pseudoglioma.[1]
Genetics
This condition is caused by autosomal recessive missense mutations in the LRP5 gene, located in the long arm of chromosome 11.[5][6]
This gene normally provides instructions to make a protein that embeds itself in the outer membrane of various cell types. It works alongside a different receptor protein, frizzled-4 (which is made by the FZD4 gene) to send chemical signams from the outside of the cell to the nucleus of said cell. Both proteins (frizzled-4 and LRP5) participate in the Wnt signaling pathway, which are steps that are involved in the development of cells and tissues, it is important for proliferation (cell division), adhesion (cell attachment), migration (cell movement), etc. The protein LRP5 makes is important for the approppiate development and maintenance of multiple tissues. It is involved in guiding the specialization of retinal cells, in establishing proper blood supply to both the retina and the inner ear, and in regulating bone mineral density, the latter of which give strength to the bones and make them less likely to break.[5]
The mutations in this gene that cause osteoporosis-pseudoglioma either impaire the cells' ability of producing LRP5 protein or they change the single amino acids in the protein. They cannot insert themselves into the outside of the cell, which in turn doesn't let them do their function. Loss-of-function mutations in the LRP5 protein alter the chemical signaling pathways involved in normal bone formation and retinal development, which cause the abnormalities that patients with this condition show.[5]
Diagnosis
This condition can be diagnosed through genetic testing, radiographs, and eye exams.
Treatment
Treatment is done on the symptoms themselves.
Prevalence
Worldwide, this condition has an estimated prevalence of 1 out of every 2,000,000 live births.[3][7]
History
It was first discovered in 1972 by Bianchine et al. when they described 3 families with osteogenesis imperfecta, pseudoglioma, retinoblastoma, and recurrence of bone fractures.[8]
References
- ^ a b c d e "Osteoporosis-pseudoglioma syndrome: MedlinePlus Genetics". medlineplus.gov. Retrieved 2022-07-12.
- ^ "Osteoporosis-pseudoglioma syndrome — About the Disease — Genetic and Rare Diseases Information Center". rarediseases.info.nih.gov. Retrieved 2022-07-12.
- ^ a b "Orphanet: Osteoporosis pseudoglioma syndrome". www.orpha.net. Retrieved 2022-07-12.
- ^ "Osteoporosis Pseudoglioma Syndrome OPPG | Boston Children's Hospital". www.childrenshospital.org. Retrieved 2022-07-12.
- ^ a b c "LRP5 gene: MedlinePlus Genetics". medlineplus.gov. Retrieved 2022-07-12.
- ^ Ai, Minrong; Heeger, Shauna; Bartels, Cynthia F.; Schelling, Deborah K. (2005-11-01). "Clinical and Molecular Findings in Osteoporosis-Pseudoglioma Syndrome". The American Journal of Human Genetics. 77 (5): 741–753. doi:10.1086/497706. ISSN 0002-9297. PMC 1271384. PMID 16252235.
- ^ Braslavsky, Débora; Scaglia, Paula; Sanguineti, Nora; Aza-Carmona, Miriam; Nevado Blanco, Julián; Lapunzina Badia, Pablo D.; Fernández, María Del C.; Ruiz, Olivia; Carmona, Alejandra; Szlago, Marina; Arberas, Claudia (2020-06-01). "[Osteoporosis-pseudoglioma Syndrome: a pediatric case of primary osteoporosis]". Archivos Argentinos de Pediatria. 118 (3): e300–e304. doi:10.5546/aap.2020.e300. ISSN 1668-3501. PMID 32470270. S2CID 241377642.
- ^ "Entry - #259770 - Osteoporosis-pseudoglioma syndrome; OPPG — OMIM". www.omim.org. Retrieved 2022-07-12.
Further reading
- Papadopoulos, Iordanis; Bountouvi, Evangelia; Attilakos, Achilleas; Gole, Evangelia; Dinopoulos, Argirios; Peppa, Melpomeni; Nikolaidou, Polyxeni; Papadopoulou, Anna (2018-11-29). "Osteoporosis-pseudoglioma syndrome: clinical, genetic, and treatment-response study of 10 new cases in Greece". European Journal of Pediatrics. 178 (3). Springer Science and Business Media LLC: 323–329. doi:10.1007/s00431-018-3299-3. ISSN 0340-6199.
- Tüysüz, B.; Bursalı, A.; Alp, Z.; Suyugül, N.; Laine, C.M.; Mäkitie, O. (2012). "Osteoporosis-Pseudoglioma Syndrome: Three Novel Mutations in the LRP5 Gene and Response to Bisphosphonate Treatment". Hormone Research in Paediatrics. 77 (2): 115–120. doi:10.1159/000336193. ISSN 1663-2818.