Deep phenotypic characterization of the retinal dystrophy in patients with RNU4ATAC-associated Roifman syndrome

Eye (Lond). 2023 Dec;37(18):3734-3742. doi: 10.1038/s41433-023-02581-1. Epub 2023 May 24.


Purpose: To characterize the retinal phenotype in RNU4ATAC-associated Roifman syndrome.

Methods: Ten patients (including 8 males) with molecularly confirmed Roifman syndrome underwent detailed ophthalmologic evaluation including fundus imaging, fundus autofluorescence (FAF) imaging, spectral-domain optical coherence tomography (SD-OCT), and electroretinography (ERG). Six patients had follow-up eye exams. All patients also underwent comprehensive examination for features of extra-retinal Roifman syndrome.

Results: All patients had biallelic RNU4ATAC variants. Nyctalopia was common (7/10). Visual acuity at presentation ranged from 20/20 to 20/200 (Age Range: 5-41 years). Retinal exam revealed features of generalized retinopathy with mid-peripheral pigment epithelial changes. A para or peri-foveal ring of hyper-autofluorescence was the commonest FAF abnormality noted (6/8). The SD-OCT demonstrated relative preservation of the foveal ellipsoid zone in six cases; associated features included cystoid changes (5/10) and posterior staphyloma (3/10). The ERG was abnormal in all patients; nine showed generalized rod-cone dystrophy, whilst one patient with sectoral retinal involvement only had isolated rod dystrophy (20 years old). On follow-up examination (Mean duration: 8.16 years), progressive loss of visual acuity (2/6), mid-peripheral retinal atrophy (3/6) or shortening of ellipsoid zone width (1/6) were observed.

Conclusion: This study has characterized the retinal phenotype in RNU4ATAC-associated Roifman syndrome. Retinal involvement is universal, early-onset, and overall, the retinal and FAF features are consistent with rod-cone degeneration that is slowly progressive over time. The sub-foveal retinal ultrastructure is relatively preserved in majority of patients. Phenotypic variability independent of age exists, and more study of allelic- and sex-based determinants of disease severity are necessary.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Child, Preschool
  • Electroretinography
  • Fluorescein Angiography
  • Humans
  • Male
  • Osteochondrodysplasias*
  • Phenotype
  • Retina
  • Retinal Dystrophies* / diagnosis
  • Retinal Dystrophies* / genetics
  • Tomography, Optical Coherence / methods
  • Young Adult

Supplementary concepts

  • Roifman syndrome