RESUMEN
Purpose: Cone-rod dystrophies (CORD) are inherited retinal dystrophies characterized by primary cone degeneration with secondary rod involvement. We report two patients from the same family with a dominant variant in the guanylate cyclase 2D (GUCY2D) gene with different phenotypes in the electroretinogram (ERG). Observations: A 21-year-old lady (Patient 1) was referred due to experiencing blurry vision and color vision impairment. Visual field testing revealed a central scotoma. Spectral-domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF) documented macula dysfunction. Reduced amplitude was observed in the photopic responses of ERG. Her 54-year-old father (Patient 2) had similar issues with blurry vision. A dilated fundus examination displayed bilateral macular atrophy. Loss of the ellipsoid zone line and collapse of the outer nuclear segment were noted on the SD-OCT. Photopic ERG responses were extinguished, and an electronegative ERG was observed in the dark-adapted 3.0 ERG. The gene report revealed a c.2512C > T (p.Arg838Cys) variant in GUCY2D for both patients. They were respectively diagnosed as cone dystrophy (COD) and cone-rod dystrophy (CORD). Conclusions: We report two different clinical phenotypes in GUCY2D-associated COD despite sharing the same variant. A dysfunction in the synaptic junction between the photoreceptor and the secondary neuron was proposed to explain the electronegative ERG. This explanation might extend to other gene-related cases of CORD with electronegative ERG.
RESUMEN
The CRB1 gene plays a role in retinal development and its maintenance. When disrupted, it gives a range of phenotypes such as early-onset severe retinal dystrophy/Leber congenital amaurosis (EOSRD/LCA), retinitis pigmentosa (RP), cone-rod dystrophy (CORD) and macular dystrophy (MD). Studies in CRB1 retinopathies have shown thickening and coarse lamination of retinal layers resembling an immature retina. Its role in foveal development has not yet been described; however, this retrospective study is the first to report foveal hypoplasia (FH) presence in a CRB1-related retinopathy cohort. Patients with pathogenic biallelic CRB1 variants from Moorfields Eye Hospital, London, UK, were collected. Demographic, clinical data and SD-OCT analyses with FH structural grading were performed. A total of 15 (48%) patients had EOSRD/LCA, 11 (35%) MD, 3 (9%) CORD and 2 (6%) RP. FH was observed in 20 (65%; CI: 0.47-0.79) patients, all of whom were grade 1. A significant difference in BCVA between patients with FH and without was found (p = 0.014). BCVA continued to worsen over time in both groups (p < 0.001), irrespective of FH. This study reports FH in a CRB1 cohort, supporting the role of CRB1 in foveal development. FH was associated with poorer BCVA and abnormal retinal morphology. Nonetheless, its presence did not alter the disease progression.