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Reduced bone mineral density and hyaloid vasculature remnants in a consanguineous recessive FEVR family with a mutation in LRP5

L M Downey^1,2,*, H M Bottomley^2,*, E Sheridan³, M Ahmed³, D F Gilmour¹, C F Inglehearn², A Reddy⁴, A Agrawal¹, J Bradbury⁴ and C Toomes²

¹ Department of Ophthalmology, Leeds General Infirmary, Leeds, UK
² Section of Ophthalmology and Neuroscience, Leeds Institute of Molecular Medicine, University of Leeds, Leeds, UK
³ Department of Clinical Genetics, St James’s University Hospital, Leeds, UK
⁴ Department of Ophthalmology, Bradford Royal Infirmary, Bradford, UK

Correspondence to:
Correspondence to:
Dr Carmel Toomes
Section of Ophthalmology and Neuroscience, Leeds Institute of Molecular Medicine, St James’s University Hospital, Leeds LS9 7TF, UK; c.toomes{at}leeds.ac.uk

Background/aims: Familial exudative vitreoretinopathy (FEVR) is an inherited blinding condition characterised by abnormal development of the retinal vasculature. FEVR has multiple modes of inheritance, and homozygous mutations in LRP5 have recently been reported as underlying the recessive form of this disease. The aim of this study was to examine LRP5 in a consanguineous recessive FEVR family and to clarify the eye and bone phenotype associated with recessive FEVR.

Methods: All family members were examined by slit lamp biomicroscopy and indirect ophthalmoscopy. Linkage to LRP5 was determined by genotyping microsatellite markers, constructing haplotypes and calculating lod scores. Mutation screening of LRP5 was performed by polymerase chain reaction amplification of genomic DNA followed by direct sequencing. Bone mineral density (BMD) was evaluated in all family members using dual energy x ray absorptiometry (DEXA).

Results: The clinical features observed in this family were consistent with a diagnosis of recessive FEVR. A homozygous LRP5 missense mutation, G550R, was identified in all affected individuals and all unaffected family members screened were heterozygous carriers of this mutation. Reduced BMD, hyaloid vasculature remnants, and nystagmus were features of the phenotype.

Conclusion: Recessive mutations in LRP5 can cause FEVR with reduced BMD and hyaloid vasculature remnants. Assessment of a patient with a provisional diagnosis of FEVR should therefore include investigation of BMD, with reduced levels suggestive of an underlying LRP5 mutation.

Abbreviations: BMD, bone mineral density; DEXA, dual energy x ray absorptiometry; EUA, examination under anaesthesia; FEVR, familial exudative vitreoretinopathy; OPPG, osteoporosis pseudoglioma syndrome; PCR, polymerase chain reaction; PHPV, persistent hyperplastic primary vitreous

Keywords: familial exudative vitreoretinopathy; LRP5; bone density; hyaloid vasculature

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