Familial exudative vitroretinopathy (FEVR)

(OMIM phenotype number #601813)

Familial exudative vitroretinopathy (FEVR) is an inherited disorder, caused by mutation in the LRP5 gene. FEVR is characterized by an abnormal development of the retinal vessels, particularly in the temporal retinal periphery, resulting to several variable manifestations, ranging from asymptomatic to complete blindness. Visual problems are caused by this progressive vascular anomalies and by various complications such as retinal neovascularization, exudates, fibrovascular proliferation, retinal folds, optic disc dragging, and retinal detachment. FZD4, LRP5, and TSPAN12 genes mutations, have been described as responsible for autosomal dominant form of FEVR, LRP5 gene mutation for autosomal recessive form, and NDP gene mutation for X-linked form. The encoded proteins of these four genes are involved in the wingless (Wnt) signaling pathway, which monitor retinal vascular development. Recessive LRP5 mutations are known to be responsible of osteoporosis pseudoglioma syndrome (OPPG) (see also OPPG), characterized by low bone mass and congenital or infancy onset blindness. Similarly, low bone mass has been described also in the heterozygous mutation carriers in OPPG families and in FEVR patients with dominant LRP5 mutations.

Gene

LRP5 gene, 11q13.1 (OMIM gene/locus number #603506). LRP5 gene, encoding low-density lipoprotein receptor-related protein 5.

Phenotype

Decreased visual acuity, blindness, falciform retinal folds, tractional retinal detachment, macular ectopia, retinal exudates, vitreous detachment, subcapsular opacities peripheral retinal avascularization, neovascularization, vitreous hemorrhage, horizontal pendular nystagmus, and decreased bone mineral density.

Images

Fig. Clinical pictures of family members showing classic features of FEVR. (A) Fundus photograph of the proband’s left eye taken at age 17. White glial tisssue is visible at the disc with the suggestion of a hyaloid artery remnant running forward into the vitreous. (B, C) Fundus photographs of an other patient taken at age 12. In the right eye (B) a strand within the vitreous associated with glial tissue appears to obscure the posterior pole. In the left eye (C) there is slight straightening of the temporal arcades. (D) Fundus photograph of the right eye of an other patien taken at age 10. Extensive vitreoretinal traction is seen distorting the retinal vessels emerging from the disc and producing a ‘‘dragged disc’’ appearance.

Reproduced from Br J Ophthalmol,Paul SA, Simon SS, Karthik AK, et al., volume 90, pages 1163-7, copyright notice 2006 with permission from BMJ Publishing Group Ltd.

Other resources : 

http://www.fevr.net/

 

References

  1. Downey LM, Bottomley HM, Sheridan E, et al. Reduced bone mineral density and hyaloid vasculature remnants in a consanguineous recessive FEVR family with a mutation in LRP5. Br J Ophthalmol. 2006 Sep;90(9):1163-7.
  2. Nikopoulos K, Venselaar H, Collin RW, et al. Overview of the mutation spectrum in familial exudative vitreoretinopathy and Norrie disease with identification of 21 novel variants in FZD4, LRP5, and NDP. Hum Mutat. 2010 Jun;31(6):656-66.
  3. Fei P, Zhang Q, Huang L, et al. Identification of two novel LRP5 mutations in families with familial exudative vitreoretinopathy. Mol Vis. 2014 Mar 29;20:395-409.
  4. Yang H, Li S, Xiao X, et al. Identification of FZD4 and LRP5 mutations in 11 of 49 families with familial exudative vitreoretinopathy. Mol Vis. 2012;18:2438-46.
  5. Masi L, Agnusdei D, Bilezikian J et al. Taxonomy of rare genetic metabolic bone disorders. Osteoporos Int. 2015 Jun 13.
  6. http://www.omim.org