Ocular Phenotype Correlations in Patients with TWIST versus FGFR3 Genetic Mutations

Abstract

Purpose: Infantile esotropia is associated with nasotemporal asymmetries of pursuit during monocular viewing. The purpose of this study was to determine how the duration of binocular decorrelation, which can be strictly controlled in primates, influences directional pursuit asymmetries. Methods: Optical strabismus was created in seven infant macaques by fitting them with prism goggles on DOL 1. The goggles were removed after 3 weeks (n ϭ 2), 3 months (n ϭ 1), or 6 months (n ϭ 2), emulating surgical repair of strabismus in humans at 3, 12, and 24 months of age, respectively. Two control monkeys wore plano lenses. After the goggles were removed, horizontal pursuit was recorded using search coils, evoked by "stepramp" target motion. A nasal bias index (NBI) was calculated as (Sn Ϫ St)/(Sn ϩ St), where Sn is nasally directed and St is temporally directed mean eye speed. Results: Each animal in the 3-and 6-month-duration groups showed asymmetries of pursuit at both target speeds. The longer the duration, the more severe the asymmetry: for 15 deg/s targets, the NBI in the 6-month group was 5ϫ greater than that in the 3-month group, and 30ϫX greater than that in the 3-week group (ANOVA, P ϭ 0.03). For 30 deg/s target motion, the NBI in the 6-month-duration group was 4ϫ greater than that in the 3-month group, and 12ϫ greater than that in the 3-week group (ANOVA, P ϭ 0.05). Controls had symmetric pursuit. Conclusions: Early correction of strabismus (ie, elimination of binocular decorrelation) prevents maldevelopment of the pursuit system. These findings indicate that early correction of infantile strabismus is beneficial for brain development.

Ontogenesis of the tear drainage system requires Prickle 1-driven polarized basement membrane (BM) deposition

“…It is The copyright holder for this preprint this version posted April 7, 2020. ; https://doi.org/10.1101/2020.04.07.029793 doi: bioRxiv preprint To date, developmental and genetic determinants of the tear duct are still lacking. CL and NLD defects are seen in several syndromic diseases with known causal mutations [12][13][14][15][16][17][18] . Among those, mutations in FGF signaling components (FGF10, FGFR2 and FGFR3) cause hypoplasia of NLD and lacrimal puncta often with conjunctivitis as part of Lacrimo-auriculo-dento-digital (LADD) syndrome 18 .…”

Ontogenesis of the tear drainage system requires Prickle 1-controlled polarized basement membrane (BM) deposition

“…To date, developmental and genetic determinants of the tear duct are still lacking. CL and NLD defects are seen in several syndromic diseases with known causal mutations [12][13][14][15][16][17][18] . Among those, mutations in FGF signaling components (FGF10, FGFR2 and FGFR3) cause hypoplasia of NLD and lacrimal puncta often with conjunctivitis as part of Lacrimo-auriculo-dento-digital (LADD) syndrome 18 .…”

Obstructed tear duct causes epiphora and precocious eyelid opening due to disruption of Prickle 1-mediated Wnt/PCP signaling

“…Genetic risk factors for CNLDO are poorly known. There are several scattered reports of CNLDO in syndromic diseases, suggesting existence of the genetic elements for CNLDO (Foster et al, 2014;Inan et al, 2006;Jadico et al, 2006a;Jadico et al, 2006b;Kozma et al, 1990;Rohmann et al, 2006;van Genderen et al, 2000). For instance, mutations in FGF signaling components (FGF10, FGFR2 and FGFR3) lead to Lacrimo-auriculodento-digital (LADD) syndrome exhibiting hypoplastic NLD and puncta, often in conjunction with conjunctivitis (Rohmann et al, 2006).…”