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

ABSTRACT

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.