Introduction:
Neural retinal zipper (NRL) is a developmental retinal gene and is a rare cause of retinal dystrophy. We describe the ocular phenotype in three patients from two families with novel mutations in NRL resulting in an enhanced S-cone syndrome (ESCS). Visual electrophysiology recordings in ESCS have traditionally been identified as being specific for the gene NR2E3. Recently cases of autosomal recessive NRL mutations have been described resulting in an ESCS phenotype.
Methods:
Investigations included electrophysiology, best corrected visual acuity (BCVA), optical coherence tomography (OCT) and ultra-wide field autofluorescence (UWAF) and color imaging.
Results:
Family 1 I1 (Male) initially with symptoms from age 5 years. BCVA was 6/120 in both eyes with nystagmus. Genetic testing identified a novel homozygous likely pathogenic NRL variant c.256G>T;p.Glu86*.
Family 2 II1 and II2 (Female aged 4.5 and Male 3 years) presented with nyctalopia and microphthalmia. BCVA 3/6 Kay pictures both eyes. Genetic testing identified NRL pathogenic variants, c.223dup p.Leu75Profs* and c.16del p.Ser6Alfs*13.
Electrophysiology, UWAF and OCT findings in these patients were consistent with the classical features of ESCS.
Discussion:
NRL activates and acts upstream of rod specific transcription factor NR2E3 to guide the developing photoreceptor into the rod lineage. This interaction contributes to the clinical phenotype of ESCS for NRL in addition to NR2E3.
Conclusion
We described the ocular phenotype in two families with Biallelic NRL genetic variants. These two families expand the genotypic and phenotypic spectrum of Enhanced S cone Syndrome, confirming that NRL is another gene to cause ESCS.