The distinct optic disk and peripapillary appearance in Donnai–Barrow syndrome

Introduction: Biallelic mutations in low-density lipoprotein-related protein 2 (LRP2) cause the multi-system Donnai–Barrow syndrome (facio-oculo-acoustico-renal syndrome). Although Donnai–Barrow syndrome is recognized as a form of vitreo-retinopathy, the ocular phenotype has not been well defined. The purpose of this study is to document the disk and peripapillary appearance in Donnai–Barrow syndrome. Methods: Retrospective cases series (five children with low vision from a consanguineous Emirati family known to harbor LRP2 mutation (NM_004525.2: c.7564T>C; p.Y42522H)). Results: All five children had high myopia (spherical equivalent from −15 to −22). One had an ophthalmic phenotypic pathognomonic for Knobloch syndrome, and genetic testing confirmed a homozygous novel COL18A1 mutation (NM_130455.3: c.2978_2987del; p.Pro993Leufs*35) with heterozygosity for the LRP2 mutation. The other four children, confirmed to be homozygous for the LRP2 mutation, had hypertelorism and down-slanting palpebral fissures. Three had spontaneous retinal detachment (two bilateral and one unilateral) with complicated post-surgical courses following retinal detachment repair. The three eyes (two children) without retinal detachment had a consistent unique optic nerve head appearance, with thin emanating vessels and multiple rings of depigmentation that made it difficult to discern the edge of the apparently small and recessed neuroretinal rim. This distinct appearance was also present in the post-surgical eyes which were not phthisical and seemed present in the single published posterior pole image found during literature review. Conclusions: A distinctive optic nerve head dysgenesis is part of Donnai–Barrow syndrome and can help distinguish its ocular phenotype from other vitreo-retinopathies associated with high myopia.