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. 2024 Aug 1;65(10):40.
doi: 10.1167/iovs.65.10.40.

Frequency and Genetic Spectrum of Inherited Retinal Dystrophies in a Large Dutch Pediatric Cohort: The RD5000 Consortium

Pam A T Heutinck  1 , L Ingeborgh van den Born  2 , Maikel Vermeer  1   3 , Adriana I Iglesias Gonzales  4 , Carel B Hoyng  5 , Jan Willem R Pott  6 , Hester Y Kroes  7 , Mary J van Schooneveld  8   9 , Camiel J F Boon  8   10 , Maria M van Genderen  9   11 , Astrid S Plomp  12 , Yvonne de Jong-Hesse  8   10 , Michelle B van Egmond-Ebbeling  11 , Lies H Hoefsloot  4 , Arthur A Bergen  12 , Caroline C W Klaver  1   3   5   13 , Magda A Meester-Smoor  1   3 , Alberta A H J Thiadens  1 , Virginie J M Verhoeven  1   4
Affiliations

Frequency and Genetic Spectrum of Inherited Retinal Dystrophies in a Large Dutch Pediatric Cohort: The RD5000 Consortium

Pam A T Heutinck et al. Invest Ophthalmol Vis Sci. .

Erratum in

Abstract

Purpose: Gene-based therapies for inherited retinal dystrophies (IRDs) are upcoming. Treatment before substantial vision loss will optimize outcomes. It is crucial to identify common phenotypes and causative genes in children. This study investigated the frequency of these in pediatric IRD with the aim of highlighting relevant groups for future therapy.

Methods: Diagnostic, genetic, and demographic data, collected from medical charts of patients with IRD aged up to 20 years (n = 624, 63% male), registered in the Dutch RD5000 database, were analyzed to determine frequencies of phenotypes and genetic causes. Phenotypes were categorized as nonsyndromic (progressive and stationary IRD) and syndromic IRD. Genetic causes, mostly determined by whole-exome sequencing (WES), were examined. Additionally, we investigated the utility of periodic reanalysis of WES data in genetically unresolved cases.

Results: Median age at registration was 13 years (interquartile range, 9-16). Retinitis pigmentosa (RP; n = 123, 20%), Leber congenital amaurosis (LCA; n = 97, 16%), X-linked retinoschisis (n = 64, 10%), and achromatopsia (n = 63, 10%) were the most frequent phenotypes. The genetic cause was identified in 76% of the genetically examined patients (n = 473). The most frequently disease-causing genes were RS1 (n = 32, 9%), CEP290 (n = 28, 8%), CNGB3 (n = 21, 6%), and CRB1 (n = 17, 5%). Diagnostic yield after reanalysis of genetic data increased by 7%.

Conclusions: As in most countries, RP and LCA are the most prominent pediatric IRDs in the Netherlands, and variants in RS1 and CEP290 were the most prominent IRD genotypes. Our findings can guide therapy development to target the diseases and genes with the greatest needs in young patients.

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Conflict of interest statement

Disclosure: P.A.T. Heutinck, None; L. Ingeborgh van den Born, None; M. Vermeer, None; A.I. Iglesias Gonzales, None; C.B. Hoyng, None; J.W.R. Pott, None; H.Y. Kroes, None; M.J. van Schooneveld, None; C.J.F. Boon, None; M.M. van Genderen, None; A.S. Plomp, None; Y. de Jong-Hesse, None; M.B. van Egmond-Ebbeling, None; L.H. Hoefsloot, None; A.A. Bergen, None; C.C.W. Klaver, None; M.A. Meester-Smoor, None; A.A.H.J. Thiadens, None; V.J.M. Verhoeven, None

Figures

Figure 1.
Figure 1.
Frequencies of IRD phenotypes in patients ≤20 years old in the Netherlands. Colors represent IRD subgroups: blue = progressive IRD, purple = stationary IRD, and orange = syndromic IRD.
Figure 2.
Figure 2.
Frequencies of identified genetic causes of IRD in patients ≤20 years old in the Netherlands. mtDNA, mitochondrial DNA.
Figure 3.
Figure 3.
Frequency of disease-causing genes within each phenotypic group, considering IRD with multiple genes involved, with a focus on phenotypic groups with conclusive genetic results for over 10 patients.
See this image and copyright information in PMC

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