LRP5 gene


Gene (OMIM No.)
Function of gene/protein
  • Protein: low density-lipoprotein receptor related protein 5
  • Forms a receptor complex with FZD4 as part of the Wnt/beta-catenin signaling pathway, which is required for tissue development including cell division and movement
  • Important for retinal vascular growth, remodelling and maintenance
  • Regulates bone mineral density
Clinical phenotype
(OMIM phenotype no.)
  • Exudative vitreoretinopathy 4 (#601813)
  • Osteoporosis-pseudoglioma syndrome (#259770)
  • Both phenotypes may be part of a spectrum of the same disorder caused by mutations in LRP5
  • Autosomal dominant
  • Autosomal recessive
Ocular features
  • Familial exudative vitreoretinopathy (FEVR) of variable severity
  • Retrolental fibrotic mass
  • Retinal folds extending from temporally from the disc to the anterior periphery
  • Macula dragging
  • Subretinal exudation
  • Retinal neovascularisation
  • Retinal breaks
  • Rhegmatogenous or tractional retinal detachments
Systemic features
  • Reduced bone density/osteoporosis of variable severity
Key investigations
  • Fluorescein angiography to determine areas of non-perfusion in the peripheral retina
  • Electrophysiology to determine visual potential
  • B-scan USS to identify any posterior segment abnormalities (e.g retinal detachment) if presence of retrolental mass prevents a detailed fundal examination
  • DEXA bone scan to assess bone density
  • Developmental assessment
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (Retinal)
  • Whole exome sequencing
  • Whole genome sequencing
  • Laser to all areas of non-perfusion especially in eyes with visual potential
  • Retinal detachments should be treated with an encircling buckle instead of a vitrectomy where possible; vitrectomy may be required for posterior breaks
  • Medications for bone protection if osteoporosis is detected on DEXA scan
Therapies under research
  • None at present
Further information

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  9.  Toomes C, Bottomley HM, Jackson RM, et al. Mutations in LRP5 or FZD4 underlie the common familial exudative vitreoretinopathy locus on chromosome 11q. Am J Hum Genet. 2004;74(4):721-730
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  12.  Gilmour DF. Familial exudative vitreoretinopathy and related retinopathies. Eye (Lond). 2015;29(1):1-14

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Updated on January 18, 2021
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