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.

Association of Pediatric Strabismus and Functional Impairment: A Cross-sectional Nationwide Analysis.

PURPOSE: To examine the association of childhood strabismus with functional limitation to identify particular domains of impairment. METHODS: The authors analyzed 201 children ages 5 to 17 years with strabismus enrolled in the 1996-2015 Medical Expenditure Panel Surveys, representative annual surveys of the U.S. POPULATION: Functional impairment was assessed using the Columbia Impairment Scale (CIS), a validated measure of behavioral and psychosocial functioning. A CIS score of 16 or greater defined clinically significant functional impairment. Multivariate regression models adjusted for age, sex, race, ethnicity, household income, geographic location, and insurance type were constructed to examine the association of strabismus diagnosis with overall impairment and individual domains of function. RESULTS: Children diagnosed as having strabismus had higher rates of clinically significant functional impairment compared to those without strabismus (15.1% vs 9.1%, adjusted odds ratio [95% CI]: 1.82 [1.11 to 2.97], P = .02). Moreover, strabismus diagnosis was associated with higher rates of problems with getting along with their mother (1.70 [1.21 to 2.40], P = .003) and father (1.66 [1.16 to 2.38], P = .006), getting along with other children (1.67 [1.16 to 2.40], P = .006), behavior at home (1.94 [1.37 to 2.74], P = .0002), staying out of trouble (1.52 [1.04 to 2.23], P = .03), nervousness (1.49 [1.05 to 2.11], P = .02), and getting involved with sports and hobbies (1.55 [1.03 to 2.34], P = .04). CONCLUSIONS: Childhood strabismus is associated with 1.8-fold greater odds of clinically significant functional impairment, with greater dysfunction in specific relationship and behavioral domains. Functional burden may be an important consideration in management decisions. [J Pediatr Ophthalmol Strabismus. 2023;60(4):268-276.].

Acquired Brown syndrome following COVID-19 infection in a child.

Coronavirus disease 2019 (COVID-19) is a highly virulent multisystem disease caused by the SARS-CoV-2 virus. Symptoms of COVID-19 infection commonly include fever, malaise, cough, and shortness of breath. Numerous manifestations affecting nearly every organ system have been described. Ophthalmic manifestations, though rare, have been reported, including, most commonly, conjunctivitis in both adults and children, which often occurs as part of a multisystem inflammatory syndrome in children. However, pediatric ocular findings of COVID-19 are poorly understood. We present a case of acquired Brown syndrome in a child following COVID-19 infection.

The Ophthalmology Mini-Elective Gives Vision to Preclinical Medical Students.

Introduction: Ophthalmology education during medical school is often very limited. To provide exposure to areas beyond its standard curriculum, the University of Pittsburgh School of Medicine offers mini-elective courses in various disciplines. We developed such a course to provide instruction in the basics of clinical ophthalmology to interested preclinical medical students. Methods: First- and second-year medical students electively enrolled in our course (mean number of students per year = 12), which included four sessions combining didactics and hands-on learning. Additionally, each student individually spent time with an ophthalmologist in the operating room. Our course was held each year from 2015 to 2019. Results: Participants completed pre- (n = 25) and postsurveys (n = 20), reflecting increased comfort with the ophthalmologic history and physical examination. In 2019, participants also completed pre- and posttests, demonstrating increased knowledge of ophthalmology. Discussion: The Ophthalmology Mini-Elective is a unique educational tool that introduces the principles of ophthalmology to preclinical medical students, addressing an area of medicine that is generally minimally included in the required curriculum.

Depletion of macrophages in CD11b diphtheria toxin receptor mice induces brain inflammation and enhances inflammatory signaling during traumatic brain injury.

Immune cells have important roles during disease and are known to contribute to secondary, inflammation-induced injury after traumatic brain injury. To delineate the functional role of macrophages during traumatic brain injury, we depleted macrophages using transgenic CD11b-DTR mice and subjected them to controlled cortical impact. We found that macrophage depletion had no effect on lesion size assessed by T2-weighted MRI scans 28 days after injury. Macrophage depletion resulted in a robust increase in proinflammatory gene expression in both the ipsilateral and contralateral hemispheres after controlled cortical impact. Interestingly, this sizeable increase in inflammation did not affect lesion development. We also showed that macrophage depletion resulted in increased proinflammatory gene expression in the brain and kidney in the absence of injury. These data demonstrate that depletion of macrophages in CD11b-DTR mice can significantly modulate the inflammatory response during brain injury without affecting lesion formation. These data also reveal a potentially confounding inflammatory effect in CD11b-DTR mice that must be considered when interpreting the effects of macrophage depletion in disease models.