Pediatric cataract, myopic astigmatism, familial exudative vitreoretinopathy and primary open-angle glaucoma co-segregating in a family
Mackey, DA and Hewitt, AW and Ruddle, JB and Vote, B and Buttery, RG and Toomes, C and Metlapally, R and Li, YJ and Tran-Viet, KN and Malecaze, F and Calvas, P and Rosenberg, T and Guggenheim, JA and Young, TL, Pediatric cataract, myopic astigmatism, familial exudative vitreoretinopathy and primary open-angle glaucoma co-segregating in a family, Molecular Vision, 17 pp. 2118-2128. ISSN 1090-0535 (2011) [Refereed Article]
Purpose: To describe an Australian pedigree of European descent with a variable autosomal dominant phenotype of:
pediatric cortical cataract (CC), asymmetric myopia with astigmatism, familial exudative vitreoretinopathy (FEVR), and
primary open-angle glaucoma (POAG).
Methods: Probands with CC, FEVR, and POAG were enrolled in three independent genetic eye studies in Tasmania.
Genealogy confirmed these individuals were closely related and subsequent examination revealed 11 other family
members with some or all of the associated disorders.
Results: Twelve individuals had CC thought to be of childhood onset, with one child demonstrating progressive lenticular
opacification. One individual had severe retinal detachment while five others had dragged retinal vessels. Seven
individuals had POAG. Seven individuals had myopia in at least one eye ¡Ü-3 Diopters. DNA testing excluded mutations
in myocilin, trabecular meshwork inducible glucocorticoid response (MYOC) and tetraspanin 12 (TSPAN12). Haplotype
analysis excluded frizzled family receptor 4 (FZD4) and low density lipoprotein receptor-related protein 5 (LRP5), but
only partly excluded EVR3. Multipoint linkage analysis revealed multiple chromosomal single-nucleotide polymorphisms
(SNPs) of interest, but no statistically significant focal localization.
Conclusions: This unusual clustering of ophthalmic diseases suggests a possible single genetic cause for an apparently
new cataract syndrome. This family¡¯s clinical ocular features may reflect the interplay between retinal disease with
lenticular changes and axial length in the development of myopia and glaucoma.