variant results in nanophthalmos, retinitis pigmentosa, variability in foveal avascular zone.

BACKGROUND

Membrane frizzled-related protein (MFRP) plays a critical role in ocular development. mutations are known to cause nanophthalmos and, in some cases, retinitis pigmentosa, foveoschisis, and/or optic nerve head (ONH) drusen. The broad clinical spectrum of mutations necessitates further investigation of specific genotype-phenotype relationships.

MATERIALS AND METHODS

We reviewed ophthalmologic and genetic medical records of two affected siblings and one unaffected sibling.

RESULTS

Genetic testing revealed variants c.855T>A, p.(Cys285*) and c.1235T>C, p.(Leu412Pro) in in the two affected siblings. In both cases, photopic and scotopic responses were markedly reduced on electroretinogram (ERG), with greater decrease in scotopic function. Optical coherence tomography for both siblings revealed non-cystoid thickening. Blunted foveal reflexes were also observed in both siblings. Notably, foveal avascular zone abnormalities were seen on fundus autofluorescence in only one affected sibling.

CONCLUSIONS

MFRP-related ocular disease may be underrecognized due to its presentation with high hyperopia and possibly subtle retinal findings. Presence of variants c.855T>A, p.(Cys285*) and c.1235T>C, p.(Leu412Pro) in resulted in nanophthalmos and retinitis pigmentosa without associated foveoschisis or ONH drusen in our patients, consistent with the incomplete phenotype previously described in Neri et al. Abnormalities in the foveal avascular zone have been noted in other case studies and were inconsistently associated with the variants described here, representing a potential area for future investigation.