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Childhood and early onset glaucoma classification and genetic profile in a large Australasian disease registry


Knight, LSW and Ruddle, JB and Taranath, DA and Goldberg, I and Smith, JEH and Gole, G and Chiang, MY and Willett, F and D'Mellow, G and Breen, J and Qassim, A and Mullany, S and Elder, JE and Vincent, AL and Staffieri, SE and Kearns, LS and Mackey, DA and Luu, S and Siggs, OM and Souzeau, E and Craig, JE, Childhood and early onset glaucoma classification and genetic profile in a large Australasian disease registry, Ophthalmology pp. 1-12. ISSN 0161-6420 (2021) [Refereed Article]

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Copyright Statement

Copyright 2021 by the American Academy of Ophthalmology. This is an open access article under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license, ( Published by Elsevier Inc.

DOI: doi:10.1016/j.ophtha.2021.04.016


Purpose: To report the relative frequencies of childhood and early onset glaucoma subtypes and their genetic findings in a large single cohort.

Design: Retrospective clinical and molecular study.

Participants: All individuals with childhood glaucoma (diagnosed 0 to <18 years) and early onset glaucoma (diagnosed 18 to <40 years) referred to a national disease registry.

Methods: We retrospectively reviewed the referrals of all individuals with glaucoma diagnosed at <40 years of age recruited to the Australian and New Zealand Registry of Advanced Glaucoma (ANZRAG). Subtypes of glaucoma were determined using the Childhood Glaucoma Research Network (CGRN) classification system. DNA extracted from blood or saliva samples underwent sequencing of genes associated with glaucoma.

Main Outcome Measures: The phenotype and genotype distribution of glaucoma diagnosed at <40 years of age.

Results: A total of 290 individuals (533 eyes) with childhood glaucoma and 370 individuals (686 eyes) with early onset glaucoma were referred to the ANZRAG. Primary glaucoma was the most prevalent condition in both cohorts. In the childhood cohort, 57.6% of individuals (167/290, 303 eyes) had primary congenital glaucoma (PCG), and 19.3% (56/290, 109 eyes) had juvenile open-angle glaucoma. Juvenile open-angle glaucoma constituted 73.2% of the early onset glaucoma cohort (271/370, 513 eyes). Genetic testing in probands resulted in a diagnostic yield of 24.7% (125/506) and a reclassification of glaucoma subtype in 10.4% of probands (13/125). The highest molecular diagnostic rate was achieved in probands with glaucoma associated with nonacquired ocular anomalies (56.5%). Biallelic variants in CYP1B1 (n = 29, 23.2%) and heterozygous variants in MYOC (n = 24, 19.2%) and FOXC1 (n = 21, 16.8%) were most commonly reported among probands with a molecular diagnosis. Biallelic CYP1B1 variants were reported in twice as many female individuals as male individuals with PCG (66.7% vs. 33.3%, P = 0.02).

Conclusions: We report on the largest cohort of individuals with childhood and early onset glaucoma from Australasia using the CGRN classification. Primary glaucoma was most prevalent. Genetic diagnoses ascertained in 24.7% of probands supported clinical diagnoses and genetic counseling. International collaborative efforts are required to identify further genes because the majority of individuals still lack a clear molecular diagnosis.

Item Details

Item Type:Refereed Article
Keywords:childhood glaucoma, early onset glaucoma, genetic testing, glaucoma, glaucoma genetics
Research Division:Biomedical and Clinical Sciences
Research Group:Ophthalmology and optometry
Research Field:Ophthalmology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Diagnosis of human diseases and conditions
UTAS Author:Mackey, DA (Professor David Mackey)
ID Code:146702
Year Published:2021
Web of Science® Times Cited:6
Deposited By:Menzies Institute for Medical Research
Deposited On:2021-09-22
Last Modified:2022-08-25
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