Genetic testing results of children suspected to have Stickler syndrome type collagenopathy after ocular examination.

Autor: Khan AO; Department of Genetics, KFSHRC, Riyadh, Saudi Arabia.; Eye Institute, Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates.; Department of Ophthalmology, Cleveland Clinic Lerner College of Medicine of Case Western University, Cleveland, OH, USA., AlAbdi L; Department of Genetics, KFSHRC, Riyadh, Saudi Arabia.; College of Science, King Saud University, Riyadh, Saudi Arabia., Patel N; Department of Genetics, KFSHRC, Riyadh, Saudi Arabia., Helaby R; Department of Genetics, KFSHRC, Riyadh, Saudi Arabia., Hashem M; Department of Genetics, KFSHRC, Riyadh, Saudi Arabia., Abdulwahab F; Department of Genetics, KFSHRC, Riyadh, Saudi Arabia., AlBadr FB; Department of Radiology, College of Medicine, King Saud University, Riyadh, Saudi Arabia., Alkuraya FS; Department of Genetics, KFSHRC, Riyadh, Saudi Arabia.; Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
Jazyk: angličtina
Zdroj: Molecular genetics & genomic medicine [Mol Genet Genomic Med] 2021 May; Vol. 9 (5), pp. e1628. Date of Electronic Publication: 2021 May 05.
DOI: 10.1002/mgg3.1628
Abstrakt: Purpose: Stickler syndrome is a collagenopathy that is typically COL2A1-related (autosomal dominant) and less commonly related to other collagen gene mutations. Diagnosis is straightforward when a child has myopia or retinal detachment in the setting of classic diagnostic criteria such as hearing impairment, midfacial hypoplasia, and arthropathy. However, some children have primarily ocular disease with mild or no extraocular features. Such children can remain undiagnosed unless suspicion is raised by the ophthalmologist.
Methods: Retrospective consecutive case series (2014-2016) of children (<12 years old) suspected to have Stickler syndrome type collagenopathy by a single ophthalmologist and able to complete genetic testing for this possibility. Suspicion was based on vitreous abnormalities and myopia or lens opacities in the setting of prior retinal detachment, hearing impairment, or facial flatness.
Results: Average age of the 12 identified children was 8 years old (range 3-11; five boys). Average spherical equivalent for phakic eyes was -13 (range -3.5 to -30). Nine children had lens opacities or aphakia; two with aphakia also had lens subluxation or iridodonesis. Other recurrent clinical features included flat facies (12/12), hearing impairment (5/12), and prior retinal detachment (4/12). Pathogenic variants for collagenopathy were uncovered in 10/12 children: COL11A1 (heterozygous) in six, COL2A1 (heterozygous) in two, and COL9A1 (homozygous) in two. One child was homozygous for pathogenic variation in LRPAP1. One child had no detectable gene mutations.
Conclusions: Taken together, these clinical features (particularly vitreous abnormality, myopia, and lens opacity) had a high molecular yield for collagen gene mutation. Ophthalmologists who see such children should suspect Stickler syndrome, even in the absence of overt systemic disease. COL11A1-related rather than COL2A1-related autosomal dominant disease may be more common when undiagnosed children are identified based on ocular examination. Biallelic mutations in LRPAP1 can result in a phenotype that may resemble Stickler syndrome.
(© 2021 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)
Databáze: MEDLINE
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