Congenital Stationary Night Blindness: Clinical and Genetic Features

Abstract

Congenital stationary night blindness (CSNB) is an inherited retinal disease (IRD) that causes night blindness in childhood with heterogeneous genetic, electrophysical, and clinical characteristics. The development of sequencing technologies and gene therapy have increased the ease and urgency of diagnosing IRDs. This study describes seven Taiwanese patients from six unrelated families examined at a tertiary referral center, diagnosed with CSNB, and confirmed by genetic testing. Complete ophthalmic exams included best corrected visual acuity, retinal imaging, and an electroretinogram. The effects of identified novel variants were predicted using clinical details, protein prediction tools, and conservation scores. One patient had an autosomal dominant CSNB with a RHO variant; five patients had complete CSNB with variants in GRM6, TRPM1, and NYX; and one patient had incomplete CSNB with variants in CACNA1F. The patients had Riggs and Schubert-Bornschein types of CSNB with autosomal dominant, autosomal recessive, and X-linked inheritance patterns. This is the first report of CSNB patients in Taiwan with confirmed genetic testing, providing novel perspectives on molecular etiology and genotype-phenotype correlation of CSNB. Particularly, variants in TRPM1, NYX, and CACNA1F in our patient cohort have not previously been described, although their clinical significance needs further study. Additional study is needed for the genotype-phenotype correlation of different mutations causing CSNB. In addition to genetic etiology, the future of gene therapy for CSNB patients is reviewed and discussed.

Keywords: congenital stationary night blindness; inherited retinal disease; retinitis pigmentosa.

Figure 1

Color fundus imaging. Patient 1 presented with normal fundus photography without any bone spicules, arteriolar attenuation, or disc pallor. Color fundus imaging showed peripapillary atrophy and a temporal crescent in both eyes. Patient 2 had normal color fundus photography except a nevus in the right periphery. Patient 3′s color fundus photography showed tessellated fundus and a large optic nerve in both eyes with slightly enlarged cupping in the left eye. Patients 4–7 presented with normal fundus photography.

Figure 2

Short-wave autofluorescence (SW-AF) imaging. Each number corresponds to the patient number, with the right eye first followed by the left eye. Patients 1, 2, 6, and 7 showed normal findings. The image for patient 5 is qualitatively within the normal for AF. From the available images, patients 5, 7, and the right eye of patient 6 could be classified as granular; however, this is most likely artefactual.

Figure 3

Spectral domain optical coherence tomography (SD-OCT) imaging. Each number corresponds to the patient number, with the right eye first followed by the left eye. Patient 1 had an intact ellipsoid (EZ) line and thin choroid in both eyes. Patient 2 had intact inner and outer segment lines. Patient 3 had intact EZ lines and a normal retinal architecture in both eyes. Patient 4 had an intact EZ line in the right eye, and SD-OCT in the left eye showed no obvious defect in the anatomical structure except for a thinner retina. Patient 5 had a normal SD-OCT. Patient 6 had an overall thin retina. Patient 7 had dome-shaped macula in his right eye, and an intact EZ line in both his eyes.

Figure 4

Patients’ full field electroretinogram waveforms.

Figure 5

Phase determination for compound heterozygous patients 2–5.