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

Eye volume 37, pages 3734–3742 (2023)Cite this article

Subjects

Abstract

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.

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Fig. 1: Retinal imaging of Cases 1–5.
Fig. 2: Detailed retinal characteristics of Cases 5-10.

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Data availability

All data generated or analyzed during this study are included in this published paper. Further queries can be directed to the corresponding author.

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Acknowledgements

We thank the patients for their active participation in the study. We thank Leslie MacKeen and Cynthia VandenHoven, for their assistance with obtaining multi-modal imaging. EH is supported by the Henry Brent Chair in Innovative Pediatric Ophthalmology Research.

Funding

AV is supported by the Foundation Fighting Blindness, USA (CD-CL-0617-0727-HSC).

Author information

Authors and Affiliations

  1. Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, ON, Canada

    Brian G. Ballios, Alaa Tayyib, Elise Heon & Ajoy Vincent

  2. Division of Immunology and Allergy, The Hospital for Sick Children and the University of Toronto, Toronto, ON, Canada

    Amarilla Mandola, Jenny Garkaby & Chaim M. Roifman

  3. Department of Ophthalmology and Vision Sciences, The Hospital for Sick Children, Toronto, ON, Canada

    Alaa Tayyib, Anupreet Tumber, Elise Heon & Ajoy Vincent

  4. The Canadian Centre for Primary Immunodeficiency and The Jeffrey Modell Research Laboratory for the Diagnosis of Primary Immunodeficiency, The Hospital for Sick Children, Toronto, ON, Canada

    Linda Vong & Chaim M. Roifman

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  1. Brian G. Ballios
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Contributions

CMR and AV designed the study concept. BGB, AM, AT (ATumber), JG, EH, CMR and AV collected data. BGB, AT (ATumber) and AV analyzed the data. BGB, AM, AT (ATayyib), AT (ATumber), LV, CMR and AV wrote the first draft of the paper. All authors contributed to the final draft of the paper and approved the contents.

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Correspondence to Ajoy Vincent.

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Ballios, B.G., Mandola, A., Tayyib, A. et al. Deep phenotypic characterization of the retinal dystrophy in patients with RNU4ATAC-associated Roifman syndrome. Eye 37, 3734–3742 (2023). https://doi.org/10.1038/s41433-023-02581-1

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