Clinical and Genetic Study of X-Linked Juvenile Retinoschisis in the Czech Population

Abstract

The aim of this study was to identify RS1 pathogenic variants in Czech patients with X-linked retinoschisis (XLRS) and to describe the associated phenotypes, including natural history, in some cases. Twenty-one affected males from 17 families were included. The coding region of RS1 was directly sequenced and segregation of the identified mutations was performed in available family members. In total, 12 disease-causing variants within RS1 were identified; of these c.20del, c.275G>A, c.[375_379del; 386A>T], c.539C>A and c.575_576insT were novel, all predicted to be null alleles. The c.539C>A mutation occurred de novo. Three patients (aged 8, 11 and 19 years) were misdiagnosed as having intermediate uveitis and treated with systemic steroids. Repeat spectral domain optical coherence tomography examinations in four eyes documented the transition from cystoid macular lesions to macular atrophy in the fourth decade of life. Four individuals were treated with topical dorzolamide and in two of them, complete resolution of the cystic macular lesions bilaterally was achieved, while one patient was noncompliant. Rebound phenomenon after discontinuation of dorzolamide for 7 days was documented in one case. Misdiagnosis of XLRS for uveitis is not uncommon; therefore, identification of disease-causing variants is of considerable benefit to the affected individuals.

Longitudinal Photoreceptor Phenotype Observation and Therapeutic Evaluation of a Carbonic Anhydrase Inhibitor in a X-Linked Retinoschisis Mouse Model

“…Since cystic presence has been linked to decreased visual acuity (41), it was conjectured that CAI might improve the acuity and decrease the later-onset atrophy in XLRS, by reducing fluid accumulation in the cavities. We found CAI reduced cystic cavity volume in Rs1 −/Y mice, while no functional improvement was detected in term of ERG responses, which were comparable to the results of clinical trials in human XLRS subjects (42)(43)(44). The reasons that the discordance between the structure and function after CAI application remained unknown.…”

X-Linked Retinoschisis Masquerading Uveitis

“…XLRS represents a uveitis masquerade syndrome-the distinction between this inherited retinal disease and uveitis appears to be fundamental [6,7]. In this cohort, 4 out of 22 XLRS patients were primary diagnosed as uveitis, which is in accordance with a study by Kousal et al, reporting 3 out of 21 XLRS patients initially diagnosed as intermediate uveitis [6].…”

“…XLRS represents a uveitis masquerade syndrome-the distinction between this inherited retinal disease and uveitis appears to be fundamental [6,7]. In this cohort, 4 out of 22 XLRS patients were primary diagnosed as uveitis, which is in accordance with a study by Kousal et al, reporting 3 out of 21 XLRS patients initially diagnosed as intermediate uveitis [6]. De Carvalho Mendes Paiva et al reported an 8-month-old male initially treated for presumptive ocular toxoplasmosis, due to the loss of red reflex, vitreous opacity, and thickened posterior hyaloid, who later turned out to be an XLRS patient [7].…”

“…The most prominent UMSs are neoplastic pathologies, including vitreoretinal/intraocular lymphoma in adults and retinoblastoma in children [2,4]. However, several non-neoplastic diseases may also masquerade as uveitis, including inherited retinal diseases and X-linked retinoschisis (XLRS) [5][6][7].…”