Ocular manifestations of renal ciliopathies

Abstract

Renal ciliopathies are a common cause of kidney failure in children and adults, and this study reviewed their ocular associations. Genes affected in renal ciliopathies were identified from the Genomics England Panels. Ocular associations were identified from Medline and OMIM, and the genes additionally examined for expression in the human retina ( https://www.proteinatlas.org/humanproteome/tissue ) and for an ocular phenotype in mouse models ( http://www.informatics.jax.org/ ). Eighty-two of the 86 pediatric-onset renal ciliopathies (95%) have an ocular phenotype, including inherited retinal degeneration, oculomotor disorders, and coloboma. Diseases associated with pathogenic variants in ANK6, MAPKBP1, NEK8, and TCTN1 have no reported ocular manifestations, as well as low retinal expression and no ocular features in mouse models. Ocular abnormalities are not associated with the most common adult-onset "cystic" kidney diseases, namely, autosomal dominant (AD) polycystic kidney disease and the AD tubulointerstitial kidney diseases (ADTKD). However, other kidney syndromes with cysts have ocular features including papillorenal syndrome (optic disc dysplasia), Hereditary Angiopathy Nephropathy, Aneurysms and muscle Cramps (HANAC) (tortuous retinal vessels), tuberous sclerosis (retinal hamartomas), von Hippel-Lindau syndrome (retinal hemangiomas), and Alport syndrome (lenticonus, fleck retinopathy). Ocular abnormalities are associated with many pediatric-onset renal ciliopathies but are uncommon in adult-onset cystic kidney disease. However the demonstration of ocular manifestations may be helpful diagnostically and the features may require monitoring or treatment.

Keywords: Coloboma; Inherited retinal degeneration; Nephronophthisis; Oculomotor disorder; Renal ciliopathy.

Fig. 1

Inherited retinal degeneration in renal ciliopathies demonstrating a a waxy optic disc, attenuated arterioles, and widespread mottling of the retinal pigment epithelium in nephronophthisis; with OCT scan demonstrating outer retinal atrophy with a small area of retained subfoveal photoreceptors (below); b infrared fundus image demonstrating a ring of retained normal retina; c automated visual field test demonstrating constricted visual field; d inferonasal retinal pigmentation in an adult with Bardet-Biedl syndrome; and e retinal thinning and intraretinal pigment migration with OCT scan demonstrating associated cystoid macular edema (below)

Fig. 2

Optic disc anomalies and coloboma in renal ciliopathies demonstrating a iris coloboma and b large chorioretinal coloboma

Fig. 3

Ocular abnormalities in cystic kidney disease demonstrating a tuberous sclerosis with retinal astrocytoma and OCT with intraretinal location (below); b von Hippel-Lindau syndrome with treated hemangioma; c congenital vascular tortuosity typical of HANAC; d X-linked Alport syndrome with fleck dystrophy that spares the macula, and OCT that demonstrates the temporal retinal thinning and characteristic macular profile (below); and e renal coloboma syndrome with retinal vessels emerging from the side rather than the center of the optic disc