Expanded Retinal Disease Spectrum Associated With Autosomal Recessive Mutations in GUCY2D

Am J Ophthalmol. 2018 Jun:190:58-68. doi: 10.1016/j.ajo.2018.03.021. Epub 2018 Mar 17.

Abstract

Purpose: GUCY2D has been associated with autosomal recessive Leber congenital amaurosis and autosomal dominant cone-rod dystrophy. This report expands the phenotype of autosomal recessive mutations to congenital night blindness, which may slowly progress to mild retinitis pigmentosa.

Design: Retrospective case series.

Methods: Multicenter study of 5 patients (3 male, 2 female).

Results: All patients presented with night blindness since childhood. Age at referral was 9-45 years. Length of follow-up was 1-7 years. Best-corrected visual acuity at presentation ranged from 20/15 to 20/30 and at most recent visit averaged 20/25. No patient had nystagmus or high refractive error. ISCEV standard electroretinography revealed nondetectable dark-adapted dim flash responses and reduced amplitude but not electronegative dark-adapted bright flash responses with similar waveforms to the reduced-amplitude light-adapted single flash responses. The 30 Hz flicker responses were relatively preserved. Macular optical coherence tomography revealed normal lamination in 3 patients, with abnormalities in 2. Goldmann visual fields were normal at presentation in children but constricted in 1 adult. One child showed loss of midperipheral fields over time. Fundus appearance was normal in childhood; the adult had sparse bone spicule-like pigmentation. Full-field stimulus testing (FST) revealed markedly decreased retinal sensitivity to light. Dark adaptation demonstrated lack of rod-cone break. Two patients had tritanopia. All 5 had compound heterozygous mutations in GUCY2D. Three of the 5 patients harbor the Arg768Trp mutation reported in GUCY2D-associated Leber congenital amaurosis.

Conclusions: Autosomal recessive GUCY2D mutations may cause congenital night blindness with normal acuity and refraction, and unique electroretinography. Progression to mild retinitis pigmentosa may occur.

Publication types

  • Case Reports
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Cone-Rod Dystrophies / genetics
  • Dark Adaptation
  • Electroretinography
  • Eye Diseases, Hereditary / genetics*
  • Female
  • Genes, Recessive
  • Genetic Diseases, X-Linked / genetics*
  • Guanylate Cyclase / genetics*
  • Humans
  • Leber Congenital Amaurosis / genetics
  • Male
  • Middle Aged
  • Mutation*
  • Myopia / genetics*
  • Night Blindness / genetics*
  • Photic Stimulation
  • Receptors, Cell Surface / genetics*
  • Refraction, Ocular / physiology
  • Retinitis Pigmentosa / genetics*
  • Retrospective Studies
  • Visual Acuity / physiology
  • Visual Field Tests
  • Visual Fields / physiology

Substances

  • Receptors, Cell Surface
  • guanylate cyclase 1
  • Guanylate Cyclase

Supplementary concepts

  • Night blindness, congenital stationary