Abstract
Purpose :
SCLT1 gene has been reported in the pathogenesis of oral-facial-digital syndrome, Senior-Loken syndrome and Bardet-Biedl syndrome. SCLT1 encodes a linker protein associated with the sodium voltage-gated channel alpha subunit 10 and clathrin, and was identified as one of the component proteins involved in ciliogenesis. Only few patients with SCLT1-related rod-cone dystrophy have been reported. Here, we present two siblings with cone dystrophy and some features resembling ciliopathy.
Methods :
Comprehensive eye exam was performed together with fundus images, fundus autofluorescence (FAF), optical coherence tomography (OCT), color vision test, visual fields, full-field electroretinography (ffERG) and multifocal ERG. The patients were assessed for ciliopathy features including echocardiography, ultrasonography of abdomen, and blood tests for liver and kidney function, and glucose levels. Genetic testing (NGS retinal dystrophy panel, 285 genes) was performed for probands and parental testing of SCLT1 variants.
Results :
Two male children, age 10 and 8 years, were affected with ADHD and well-controlled obesity. Abnormalities of the heart, liver or kidneys, and postaxial polydactyly were not present. Children had mild light sensitivity and esotropia. Cycloplegic refraction revealed moderate hyperopia and significant astigmatism. BCVA was reduced (0.4 right eye/0.5 left eye logMAR in older patient; 0.3 logMAR both eyes in younger one) and moderate red-green color vision defects were noticed. Fundus exam was largely normal. FAF revealed decreased foveal FAF surrounded by increased FAF signal. OCT macula showed retinal thinning. Central visual field defects were observed. Further ffERG confirmed cone dystrophy. Ciliopathy was suggested as a possible diagnosis. Retinal dystrophy panel showed homozygous likely pathogenic, splice-site variant in SCLT1 gene NM_144643.3: c.1439+1del. This variant was not reported in ClinVar or gnomAD, and was heterozygous in the healthy parents.
Conclusions :
In this report, we highlight the importance of extensive diagnostics in patients with unexplained reduced vision, strabismus, refractive errors and autism/ADHD spectrum disorders. Ciliopathies may present with milder systemic and ocular phenotype and thereby can be underdiagnosed. SCLT1-related retinal degeneration is rare and cone dystrophy was not observed until now.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.