Clinical spectrum of retinal dystrophy caused by pathogenic variants in the cerkl gene

Aims/Purpose: Two disease‐causing variants of the CERKL gene, (c.375C > G, c.193G > T), are enriched in the Finnish population due to the specific population history. Here we present a large patient cohort with biallelic pathogenic variants in CERKL with long follow‐up time and a reduced spectrum of pathogenic variants.

Methods: In this retrospective cohort study medical record data were collected from 50 patients with CERKL‐associated retinopathy followed in the Department of Ophthalmology, Helsinki University Hospital. The age, sex, symptoms, onset of symptoms, best corrected visual acuity (BCVA), colour fundus photography, spectral‐domain optical coherence tomography (SD‐OCT), fundus autofluorescence (AF) and genetic data were collected.

Results: The median age at the first visit was 24 years (range 5‐51), and the follow‐up time was 12 years (median, range 0,8‐19). The most common symptoms were nyctalopia (33 patients), reduced BCVA (25 patients) and glare (24 patients). In 11 patients, the disease manifested in the macular area ranging from mild bull's eye maculopathy to geographic atrophy. In 28 patients, both macular and peripheral retina were affected. Eleven patients had severe panretinal degeneration. The median age at onset of visual impairment according to the WHO classification was 38 years (range 23‐60), which corresponds to a 14‐year period (median; range 7‐27) after receiving the diagnosis. Forty‐three (88 %) patients carried at least one allele of the most common pathogenic variant c.375C > G, and 34 (69 %) were homozygous for this variant. Twelve patients (24 %) carried at least one allele of the second most common variant, c.193G > T.

Conclusions: The disease spectrum is broad in this large CERKL‐associated retinopathy cohort ranging from macular disease to severe panretinal degeneration. The over a decade period from diagnosis to visual impairment provides an optimal time window for future therapeutic interventions.