Case report: ocular manifestations of a gain-of-function mutation in CLCN6, a newly diagnosed disease.

BACKGROUND: In 2020, a new disease was reported by Polovitskaya et al., caused by a monoallelic, gain-of-function mutation in CLCN6, encoding the ClC-6 Cl-/H±exchanger. METHODS: Here, we report the ophthalmic findings of one of the first three patients with this disease (the proband) and review the findings in the other two patients in the literature. RESULTS: The CLCN6 gene is part of the voltage-dependent chloride channel protein family. It functions as either a chloride channel aiding in cell-volume regulation and acidification of intracellular organelles or as an antiporter, which are membrane proteins involved in the transport of molecules across a phospholipid membrane. This particular gene is found in late endosomes. Ion transport across endosome membranes is essential for endosomal function. The proband carried a de novo c.1658A>G (p.Tyr553Cys) mutation in CLCN6. The patient reported herein has a notable optic nerve appearance. The nerve initially appeared elevated. Over time, the optic nerve elevation appearance decreased, associated with progressive vision loss with a visual acuity of 20/470 at last follow-up. CONCLUSION: While Clcn6-/- mice have been found to have a mild neuronal lysosomal storage phenotype, the three reported children with a de novo c.1658A>G (p.Tyr553Cys) variant displayed significant developmental delay and neurodegeneration.

Eye-related quality of life and activities of daily living in pediatric retinoblastoma patients: A single-center, non-controlled, cross-sectional analysis.

INTRODUCTION: Childhood retinoblastoma (RB) survivors are known to experience long-term morbidity; however, eye-related quality of life (QoL), which may significantly impact activities of daily living (ADL), has not been extensively studied in this population. The purpose of this cross-sectional study was to assess QoL and ADL morbidity among school-age RB survivors. METHODS: The Pediatric Eye Questionnaire (PedEyeQ) and Roll Evaluation Activities of Life (REAL) were administered to childhood RB survivors between ages 5 and 17 followed at St. Louis Children's Hospital. Visual outcomes and demographic predictors of ADL and QoL were examined. RESULTS: Total 23 patients (mean age 9.6 years) consented for participation in this study. All children experienced at least one domain on the PedEyeQ ≤ 80%. Subjects and parents marked functional vision to be the most impacted domain with a median score of 82.5 and 83.4, respectively. Only 10.5% of participants scored above 75% on the ADL percentile rank. On multivariable analysis, decreased visual acuity (VA) was associated with worse "Child Functional" (odds ratio [OR] -59.2, p = .004) and "Parent Worry Function" (OR -66.5, p = .03) metrics. Decreased contrast sensitivity was associated with worse "Parent Impact" (OR 21.0, p = .02) and "Parent Worry Function" (OR 3.70, p = .04) metrics. Longer saccade horizontal latency was associated with a worse "Parent Worry Function" metric (OR 43.0, p = .009). On multivariable analysis, no variable was significantly associated with ADL. CONCLUSION: RB survivors have impaired QoL and ADL. Screening for such difficulties should strongly be considered for all RB patients. Additional studies may help predict morbidity based on visual metrics and demographic data.