Ocular manifestations in Koolen-de Vries syndrome: an international study

Dafna Shalev; David A Koolen; Bert B A de Vries; Sharon Blum Meirovitch; Jean-Louis Mandel; Pauline Burger; Alik Rosenfeld; Guy J Ben Simon; Daphna Landau Prat

doi:10.1016/j.jcjo.2023.11.021

Ocular manifestations in Koolen-de Vries syndrome: an international study

Can J Ophthalmol. 2023 Dec 22:S0008-4182(23)00379-4. doi: 10.1016/j.jcjo.2023.11.021. Online ahead of print.

Authors

Dafna Shalev¹, David A Koolen², Bert B A de Vries², Sharon Blum Meirovitch³, Jean-Louis Mandel⁴, Pauline Burger⁵, Alik Rosenfeld⁶, Guy J Ben Simon⁷, Daphna Landau Prat⁸

Affiliations

¹ Division of Ophthalmology, Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
² Department of Human Genetics, Radboudumc, Donders Institute for Brain, Cognition, and Behavior, Nijmegen, The Netherlands.
³ Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom.
⁴ GenIDA, Institute of Genetics and Molecular and Cellular Biology (IGBMC), Department of Neurogenetics and Translational Medicine, University of Strasbourg, Illkirch, France; Institute for Advanced Studies of the University of Strasbourg (USIAS), University of Strasbourg, Strasbourg, France.
⁵ GenIDA, Institute of Genetics and Molecular and Cellular Biology (IGBMC), Department of Neurogenetics and Translational Medicine, University of Strasbourg, Illkirch, France.
⁶ Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Ophthalmology, Edith Wolfson Medical Center, Holon, Israel.
⁷ Division of Ophthalmology, Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Sheba Talpiot Medical Leadership Program, Tel Hashomer, Israel.
⁸ Division of Ophthalmology, Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Sheba Talpiot Medical Leadership Program, Tel Hashomer, Israel. Electronic address: daphna.landau@gmail.com.

PMID: 38145626
DOI: 10.1016/j.jcjo.2023.11.021

Abstract

Objectives: Koolen-de Vries Syndrome (KdVS) is a rare multisystem neurodevelopmental disorder. Ocular manifestations, including strabismus, ptosis, and hyperopia, have been reported in KdVS patients, but detailed clinical data are limited. This study aims to investigate the already known ocular malformations and their frequency while uncovering novel ocular associations.

Methods: This was an international cross-sectional study. An anonymous questionnaire was sent to 237 KdVS patients registered in the GenIDA database. The questionnaire inquired about demographic data, ocular symptoms, findings reported by ophthalmologists, and ophthalmologic surgical interventions. The main outcome measures included ocular findings and surgical interventions.

Results: Sixty-seven respondents worldwide completed the questionnaire, most (n = 53; 79%) under 18 years of age. Ophthalmologic abnormalities, noted in 79% of patients, included refractive errors (n = 35; 52.2%), strabismus (n = 23; 34.3%), amblyopia (n = 13; 19.5%), and eyelid ptosis (n = 9; 13.4%). Lacrimal disorders were present (n = 6; 9.0%), as were retinal findings (n = 7; 10.4%), including retinal hyperpigmentation or hypopigmentation (n = 4; 7.5%), Sjögren's pigment epithelial reticular dystrophy (n = 1; 1.5%), and macular chorioretinal coloboma (n = 1; 1.5%). Other manifestations included ocular surface disorders (n = 5; 7.5%), cataracts (n = 3; 4.5%), Brown syndrome (n = 1; 1.5%), glaucoma (n = 1; 1.5%), cerebral visual impairment (n = 1; 1.5%), and optic atrophy (n = 1; 1.5%). Fourteen patients (20.8%) had undergone surgical interventions.

Conclusions: KdVS is associated with various ophthalmic findings, such as amblyopia, refractive errors, strabismus, and eyelid ptosis. We describe, for the first time, a high rate of nasolacrimal disorders and retinal abnormalities consisting mainly of pigmentary findings, including a rare case of Sjögren's pigment epithelial reticular dystrophy. A comprehensive ophthalmic evaluation is therefore recommended for all KdVS patients at initial diagnosis or at 4-6 months of age for diagnosed newborns.