期刊
OPHTHALMIC GENETICS
卷 43, 期 1, 页码 48-57出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/13816810.2021.1978103
关键词
Costello syndrome; RASopathies; eye manifestations; strabismus; refractive errors; optic nerve hypoplasia
资金
- Children's Miracle Network Endowed Chair in Pediatric Genetics
- National Eye Institute/National Institutes of Health [R01EY018246]
- University of Wisconsin Centennial Scholars Award
- Research to Prevent Blindness, Inc.
Costello syndrome commonly presents with ophthalmic manifestations such as lack of stereopsis, refractive errors, strabismus, nystagmus, optic nerve abnormalities, and ptosis. Early ophthalmic evaluation and treatment are crucial for preventing long-term vision impairment and improving quality of life in individuals with this syndrome.
Background Costello syndrome (CS) is a multisystem developmental disorder caused by germline pathogenic variants in HRAS resulting in dysregulation of the Ras pathway. A systematic characterization of ophthalmic manifestations provides a unique opportunity to understand the role of Ras signal transduction in ocular development and guide optimal ophthalmic care in CS individuals. Methods Visual function, ocular features and genotype/phenotype correlations were evaluated in CS individuals harboring HRAS pathogenic variants, by cross-sectional and retrospective studies, and were recruited through the Costello Syndrome Family Network (CSFN) between 2007 and 2020. Results Fifty-six molecularly diagnosed CS individuals including 34 females and 22 males, ages ranging from 0.5 to 37 years were enrolled. The most common ophthalmic manifestations in the cross-sectional study were lack of stereopsis (96%), refractive errors (83%), strabismus (72%), nystagmus (69%), optic nerve hypoplasia or pallor (55%) and ptosis (13.7%) with higher prevalence than in the retrospective data (refractive errors (41%), strabismus (44%), nystagmus (26%), optic nerve hypoplasia or pallor (7%) and ptosis (11%)). Visual acuities were found to ranged from 20/25 to 20/800 and contrast sensitivity from 1.6% to 44%. HRAS pathogenic variants included p.G12S (84%), p.G13C (7%), p.G12A (5.4%), p.G12C (1.8%) and p.A146V (1.8%). Conclusion Majority of individuals with CS have refractive errors, strabismus, nystagmus, absent stereopsis, and optic nerve abnormalities suggesting that HRAS and the Ras pathway play a vital role in visual system development. Ptosis, refractive errors and strabismus are amenable to treatment and early ophthalmic evaluation is crucial to prevent long-term vision impairment and improve overall quality of life in CS.
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