Sleep-Disordered Breathing, Quality of Sleep and Chronotype in a Cohort of Adult Patients with Bardet–Biedl Syndrome

Abstract

Objective/Background: Bardet-Biedl syndrome (BBS) is a rare but well-recognized ciliopathy with high genetic and phenotypic heterogeneity. Cardinal features include obesity, diabetes and high blood pressure (HBP), which are often associated with sleep-disordered breathing. Also, the high prevalence of blindness due to retinal dystrophy could affect circadian sleep-wake rhythms. We characterized in this cohort of adult BBS patients sleepdisordered breathing, sleep quality, daytime sleepiness and chronotype. Patients and Methods: Thirty-two patients with genetically confirmed BBS were included in this observational single center study. Overnight respiratory polygraphy was performed for sleep apnea syndrome (SAS) in 30 patients. Quality of sleep, daytime sleepiness, fatigue and chronotype were assessed in 25 patients using Pittsburgh sleep quality index (PSQI), 14-day sleep diary (SD), Epworth sleepiness scale (ESS), Pichot fatigue scale (PFS) and Horne and Ostberg morningness-eveningness questionnaire (MEQ). Results: Patients' mean age was 32±11 years and mean BMI 32.6±7.7 kg/m 2 . Eleven (35%) patients had HBP and 7 (22%) diabetes. Moderate to severe sleep apnea syndrome (SAS) was present in 5 (17%) and was not associated with altered sleep, daytime sleepiness or fatigue. Most of the patients (63%) evaluated their sleep as of good quality (PSQI ≤ 5). Median scores of sleep quality, daytime sleepiness and fatigue were normal (PSQI of 3.0 [2.0-6.0], ESS of 9.0 [6.0-13.0] and PFS of 8.0 [3.0-13.0], respectively). Predominant chronotypes according to MEQ were either "intermediate" (57%) or "moderate morning" (29%). None had a free running sleep-wake cycle. 14-day SD revealed overall few awakenings at night and low daytime napping. Conclusions: Given the cardiovascular risk factors, systematic screening for SAS should be considered in BBS patients, regardless of sleep and daytime vigilance complaints. None of these highly visually impaired patients had a circadian sleep-wake rhythm disorder. Further objective assessments are needed to better characterize sleep and circadian rhythms in BBS patients.

Association of Sleep Pattern and Genetic Susceptibility with Obstructive Sleep Apnea: A Prospective Analysis of the UK Biobank

“… 38 Daytime sleepiness is a common symptom in obese patients with OSA, suggesting that objective daytime sleepiness is a more severe type of OSA phenotype with greater sympathetic drive, greater blood pressure, and possibly greater cardiovascular morbidity and mortality. 39 One study of 23 patients revealed that more OSA patients with mild apnea had a morning chronotype, 40 and the process of chronotype change is closely related to the prevalence of OSA. 41 Thus, it might be valuable to identify the chronotype associated with the onset of OSA in adults.…”

Diabetes mellitus in Bardet Biedl syndrome

“…In a recent observational single-centre study of 30 adults with BBS, 17% had moderate to severe sleep apnoea [19 ▪▪ ]. This study included overnight respiratory polygraphy alongside validated sleep questionnaires.…”

Ultrasound evaluation of kidney and liver involvement in Bardet-Biedl syndrome

“…Another cardinal symptom is early-onset hyperphagia-associated obesity which starts at preschool age and remains throughout life (13). Obesity in BBS patients contributes to the development of metabolic disorders such as metabolic syndrome, type 2 diabetes, (14,15,16), non-alcoholic fatty liver disease (NAFLD) and liver brosis (26-30%), all of which are related to an increased mortality at adult age (17,18). However, data to what extent liver involvement is secondary to obesity or due to dysfunctional cilia signaling like as in other related ciliopathies such as autosomalrecessive polycystic kidney disease or nephronopthisis remains unclear (19)(20)(21).…”