Sleep and circadian phenotype in people without cone-mediated vision: a case series of five CNGB3 and two CNGA3 patients

Light exposure entrains the circadian clock through the intrinsically photosensitive retinal ganglion cells, which sense light in addition to the cone and rod photoreceptors. In congenital achromatopsia (prevalence 1:30–50 000), the cone system is non-functional, resulting in severe light avoidance and photophobia at daytime light levels. How this condition affects circadian and neuroendocrine responses to light is not known. In this case series of genetically confirmed congenital achromatopsia patients (n = 7; age 30–72 years; 6 women, 1 male), we examined survey-assessed sleep/circadian phenotype, self-reported visual function, sensitivity to light and use of spectral filters that modify chronic light exposure. In all but one patient, we measured rest-activity cycles using actigraphy over 3 weeks and measured the melatonin phase angle of entrainment using the dim-light melatonin onset. Owing to their light sensitivity, congenital achromatopsia patients used filters to reduce retinal illumination. Thus, congenital achromatopsia patients experienced severely attenuated light exposure. In aggregate, we found a tendency to a late chronotype. We found regular rest-activity patterns in all patients and normal phase angles of entrainment in participants with a measurable dim-light melatonin onset. Our results reveal that a functional cone system and exposure to daytime light intensities are not necessary for regular behavioural and hormonal entrainment, even when survey-assessed sleep and circadian phenotype indicated a tendency for a late chronotype and sleep problems in our congenital achromatopsia cohort.