Osteoporosis-pseudoglioma syndrome is a rare condition characterized by severe thinning of the bones (osteoporosis) and eye abnormalities that lead to vision loss. In people with this condition, osteoporosis is usually recognized in early childhood. It is caused by a shortage of minerals, such as calcium, in bones (decreased bone mineral density), which makes the bones brittle and prone to fracture. Affected individuals often have multiple bone fractures, including in the bones that form the spine (vertebrae). Multiple fractures can cause collapse of the affected vertebrae (compressed vertebrae), abnormal side-to-side curvature of the spine (scoliosis), short stature, and limb deformities. Decreased bone mineral density can also cause softening or thinning of the skull (craniotabes).
Most affected individuals have impaired vision at birth or by early infancy and are blind by young adulthood. Vision problems are usually caused by one of several eye conditions, grouped together as pseudoglioma, that affect the light-sensitive tissue at the back of the eye (the retina), although other eye conditions have been identified in affected individuals. Pseudogliomas are so named because, on examination, the conditions resemble an eye tumor known as a retinal glioma.
Rarely, people with osteoporosis-pseudoglioma syndrome have additional signs or symptoms such as mild intellectual disability, weak muscle tone (hypotonia), abnormally flexible joints, or seizures.
Osteoporosis-pseudoglioma syndrome is a rare disorder that occurs in approximately 1 in 2 million people.
Osteoporosis-pseudoglioma syndrome is caused by mutations in the LRP5 gene. This gene provides instructions for making a protein that participates in a chemical signaling pathway that affects the way cells and tissues develop. In particular, the LRP5 protein helps regulate bone mineral density and plays a critical role in development of the retina.
LRP5 gene mutations that cause osteoporosis-pseudoglioma syndrome prevent cells from making any LRP5 protein or lead to a protein that cannot function. Loss of this protein's function disrupts the chemical signaling pathways that are needed for the formation of bone and for normal retinal development, leading to the bone and eye abnormalities characteristic of osteoporosis-pseudoglioma syndrome.
Osteoporosis-pseudoglioma syndrome is inherited in an autosomal recessive pattern, which means both copies of the LRP5 gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. However, some carriers may have decreased bone mineral density.
Other Names for This Condition
- Osteogenesis imperfecta, ocular form
Additional Information & Resources
Genetic Testing Information
Genetic and Rare Diseases Information Center
Research Studies from ClinicalTrials.gov
Catalog of Genes and Diseases from OMIM
Scientific Articles on PubMed
- Ai M, Heeger S, Bartels CF, Schelling DK; Osteoporosis-Pseudoglioma Collaborative Group. Clinical and molecular findings in osteoporosis-pseudoglioma syndrome. Am J Hum Genet. 2005 Nov;77(5):741-53. doi: 10.1086/497706. Epub 2005 Sep 27. Citation on PubMed or Free article on PubMed Central
- Gong Y, Slee RB, Fukai N, Rawadi G, Roman-Roman S, Reginato AM, Wang H, Cundy T, Glorieux FH, Lev D, Zacharin M, Oexle K, Marcelino J, Suwairi W, Heeger S, Sabatakos G, Apte S, Adkins WN, Allgrove J, Arslan-Kirchner M, Batch JA, Beighton P, Black GC, Boles RG, Boon LM, Borrone C, Brunner HG, Carle GF, Dallapiccola B, De Paepe A, Floege B, Halfhide ML, Hall B, Hennekam RC, Hirose T, Jans A, Juppner H, Kim CA, Keppler-Noreuil K, Kohlschuetter A, LaCombe D, Lambert M, Lemyre E, Letteboer T, Peltonen L, Ramesar RS, Romanengo M, Somer H, Steichen-Gersdorf E, Steinmann B, Sullivan B, Superti-Furga A, Swoboda W, van den Boogaard MJ, Van Hul W, Vikkula M, Votruba M, Zabel B, Garcia T, Baron R, Olsen BR, Warman ML; Osteoporosis-Pseudoglioma Syndrome Collaborative Group. LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development. Cell. 2001 Nov 16;107(4):513-23. doi: 10.1016/s0092-8674(01)00571-2. Citation on PubMed
- Levasseur R, Lacombe D, de Vernejoul MC. LRP5 mutations in osteoporosis-pseudoglioma syndrome and high-bone-mass disorders. Joint Bone Spine. 2005 May;72(3):207-14. doi: 10.1016/j.jbspin.2004.10.008. Citation on PubMed
- Narumi S, Numakura C, Shiihara T, Seiwa C, Nozaki Y, Yamagata T, Momoi MY, Watanabe Y, Yoshino M, Matsuishi T, Nishi E, Kawame H, Akahane T, Nishimura G, Emi M, Hasegawa T. Various types of LRP5 mutations in four patients with osteoporosis-pseudoglioma syndrome: identification of a 7.2-kb microdeletion using oligonucleotide tiling microarray. Am J Med Genet A. 2010 Jan;152A(1):133-40. doi: 10.1002/ajmg.a.33177. Citation on PubMed
- Tuysuz B, Bursali A, Alp Z, Suyugul N, Laine CM, Makitie O. Osteoporosis-pseudoglioma syndrome: three novel mutations in the LRP5 gene and response to bisphosphonate treatment. Horm Res Paediatr. 2012;77(2):115-20. doi: 10.1159/000336193. Epub 2012 Mar 23. Citation on PubMed