Foveal Hypoplasia, Chiasmal Misrouting and Anterior Segment Dysgenesis in the Absence of Albinism

Abstract

Purpose: : We have previously identified a consanguineous family (Pedigree 1) with a new phenotype of recessively inherited foveal hypoplasia and anterior segment dysgenesis (ASD) and mapped this disorder to chromosome 16q23.2-24.2. The present study describes the identification of a second consanguineous family (Pedigree 2) with this disorder and extends the clinical phenotype to include chiasmal misrouting in the absence of albinism. Further genetic analysis is performed to aid in the identification of the mutated gene.

Methods: : In addition to routine clinical evaluation, optical coherence tomography (OCT) was carried out and pattern onset visually evoked potentials (VEPs) were recorded. Genotyping was performed in all available family members using fluorescently labelled microsatellite markers from chromosome 16q and Affymetrix SNP chip analysis was performed on selected affected individuals.

Results: : All affected individuals presented in early childhood with nystagmus and poor vision secondary to foveal hypoplasia and had signs of either posterior embryotoxon or Axenfeld’s anomaly. OCT analysis, where possible, confirmed the absence of a foveal pit and VEP analysis showed abnormal chiasmal decussation. In both pedigrees the affected children had similar hair and skin colour to their parents and siblings. Linkage analysis showed that Pedigree 2 also mapped to the 16q locus. SNP chip analysis was used to refine the candidate locus to an interval of 3 Mb. Screening of candidate genes in this region is ongoing.

Conclusions: : This study described two families with ASD, foveal hypoplasia and abnormal chiasmal decussation. This combination of clinical features has not previously been described. Linkage analysis maps this disorder to a 3 Mb interval on chromosome 16q. Identification of the causative gene in these families will give valuable insights into embryogenesis of the eye and the visual system.

Keywords: gene mapping • macula/fovea • anterior segment