KCNV2 retinopathy: clinical features, molecular genetics and directions for future therapy

Abstract

KCNV2-associated retinopathy or "cone dystrophy with supernormal rod responses" is an autosomal recessive cone-rod dystrophy with pathognomonic ERG findings. This gene encodes Kv8.2, a voltagegated potassium channel subunit that acts as a modulator by shifting the activation range of the K + channels in photoreceptor inner segments. Currently, no treatment is available for the condition. However, there is a lack of prospective long-term data in large molecularly confirmed cohorts, which is a prerequisite for accurate patient counselling/prognostication, to identify an optimal window for intervention and outcome measures, and ultimately to design future therapy trials. Herein we provide a detailed review of the clinical features, retinal imaging, electrophysiology and psychophysical studies, molecular genetics, and briefly discuss future prospects for therapy trials.

KCNV2-Associated Retinopathy: Genetics, Electrophysiology, and Clinical Course—KCNV2 Study Group Report 1

“…The current study reported a further 28 novel KCNV2 variants—a significant addition to the 95 previously reported variants. 9 …”

“…The current study reported a further 28 novel KCNV2 variants which is a significant addition to the 95 previously reported variants. 9 With the recognition of the pathognomonic ERG phenotype, targeted KCNV2 screening is of high yield as previously suggested. 17 In the same study KCNV2retinopathy was identified as the second most common cause (11.3%) of paediatric inherited retinal disease (IRD) in an Emirati cohort of 71 patients.…”

“… 6 , 7 , 8 In total, we identified 114 cases described in the literature, in 22 studies and case reports. 9 Clinically, KCNV2 is characterized by variable age of onset, usually in infancy or early childhood, color vision defects (most commonly in the red–green axis), impaired adaptations to different light conditions, mild photophobia and nyctalopia. 10 , 11 , 12 , 13 , 14 , 15 In young patients, clinical presentation can be variable, the most common presentation being abnormal head position, head shaking, and nystagmus that improves with time.…”

Retinal imaging in inherited retinal diseases

“…Progressive COD/CORD are characterised by cone photoreceptor degeneration, which may be followed by subsequent rod photoreceptor loss. These disorders typically present with progressive loss of central vision, colour vision disturbance and photophobia ( 11 , 44 ). We discuss their retinal imaging, focusing on five of the most common genotypes: GUCA1A , GUCY2D , ABCA4 , PRPH2 and RPGR .…”

Long-term follow-up of a Chinese patient with KCNV2-retinopathy

“…Some patients present with color vision deficits, myopia, central scotoma, and, particularly in younger patients, nystagmus. Fundus findings are usually unremarkable in children, but adults frequently exhibit distinct macular changes or retinal pigment epithelial (RPE) atrophy (2)(3)(4)(5)(6)(7)(8)(9)(10).…”