Sleep disturbances in Wolfram syndrome

Amy Licis,Gabriel Davis,Tamara Hershey,Heather M Lugar,Sarah A Eisenstein

doi:10.1186/s13023-019-1160-z

Abstract

BackgroundWolfram syndrome is a rare disorder associated with diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing and vision loss, and neurodegeneration. Sleep complaints are common but have not been studied with objective measures. Our goal was to assess rates of sleep apnea and objective and self-reported measures of sleep quality, and to determine the relationship of sleep pathology to other clinical variables in Wolfram syndrome patients.MethodsGenetically confirmed Wolfram syndrome patients were evaluated at the 2015 and 2016 Washington University Wolfram Syndrome Research Clinics. Patients wore an actigraphy device and a type III ambulatory sleep study device and completed the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index (PSQI) and/or the Pediatric Sleep Questionnaire (PSQ). PSQI and PSQ questionnaire data were compared to a previously collected group of controls. Patients were characterized clinically with the Wolfram Unified Rating Scale (WURS) and a subset underwent magnetic resonance imaging (MRI) for brain volume measurements.ResultsTwenty-one patients were evaluated ranging from age 8.9–29.7 years. Five of 17 (29%) adult patients fit the criteria for obstructive sleep apnea (OSA; apnea-hypopnea index [AHI] ≥ 5) and all 4 of 4 (100%) children aged 12 years or younger fit the criteria for obstructive sleep apnea (AHI’s ≥ 1). Higher AHI was related to greater disease severity (higher WURS Physical scores). Higher mixed apnea scores were related to lower brainstem and cerebellar volumes. Patients’ scores on the PSQ were higher than those of controls, indicating greater severity of childhood obstructive sleep-related breathing disorders.ConclusionsWolfram syndrome patients had a high rate of OSA. Further study would be needed to assess how these symptoms change over time. Addressing sleep disorders in Wolfram syndrome patients would likely improve their overall health and quality of life.

Highlights

Wolfram syndrome is a rare disorder associated with diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing and vision loss, and neurodegeneration
Reasons for declining ambulatory sleep study testing included a prior clinical diagnosis of obstructive sleep apnea treated with continuous positive airway pressure (CPAP) nightly (n = 1), lack of availability of the ambulatory sleep monitoring device (n = 2), and anticipated discomfort with the testing (n = 4)
Both patients had been diagnosed with moderate obstructive sleep apnea by in-lab sleep studies

Summary

Introduction

Wolfram syndrome is a rare disorder associated with diabetes mellitus, diabetes insipidus, optic nerve atrophy, hearing and vision loss, and neurodegeneration. In a case series of 45 patients with the classic manifestations of diabetes insipidus, diabetes mellitus, optic atrophy, and deafness (DIDMOAD), the median age of death was 30 years (range 25–49 years) and central respiratory failure with brainstem atrophy was noted as a cause [5]. In another series of 68 patients defined by the clinical manifestations of DIDMOAD, more than 50% of the 23 patients who died had symptoms of significant neurodegeneration, including apneic spells [6]. The natural history of respiratory issues and their severity across the continuum of the disease phenotype is unclear

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