Sleep problems Usher patient appears to be a hallmark feature of the disease Vision impairment is not the driver of fatigue and sleep problems

It was always thought that fatigue and sleep problems in patients with Usher syndrome are the result of increased efforts to compensate for their dual sensory impairment: limited vision combined with hearing loss. Researchers from Radboudumc show in Ophthalmology Science that this idea is incomplete. Besides severe problems with hearing and vision, sleep problems also seem to be a hallmark feature of the disease.

Patients with Usher syndrome experience major problems with vision and hearing. They are born profound deaf or hearing impaired and around puberty they also start to slowly lose their eyesight. These are the central features of the disease. The large individual differences in disease severity and progression are closely related to the underlying genetic defect and the type of Usher syndrome. "Besides hearing and vision loss, patients occasionally also encounter some other problems, like balance deficits, but these have been recognized as part of the disease," says researcher Erwin van Wijk. "In addition, sleep problems and excessive fatigue are also regularly reported in the consulting room. The fatigue has always been regarded as a result of the dual sensory impairment that patients have to deal with. It’s generally assumed that the sleep problems often reported by patients are the result of their impaired light perception. After all, individuals with poor light perception gradually lose visual day and night rhythms, having a significant impact on their sleep quality."

Poor sleep
Researchers at Radboudumc are in close contact with patients, mainly via the Dutch Ushersyndrome Foundation. "At one point we noticed that very many patients complained about sleep problems and fatigue”, says Van Wijk. “That intrigued us. Was perhaps something else going on than we always anticipated? Under supervision of Erik de Vrieze, Juriaan Metz, Rob Collin and myself, PhD student Jessie Hendricks started a survey to further investigate this. Fifty-six Usher syndrome type 2A (USH2A) patients and 120 healthy controls were subjected to a set of five validated questionnaires to assess sleep quality, sleep disorders, fatigue, daytime sleepiness and chronotype." The results indicated that USH2A patients indeed experienced a strongly reduced sleep quality and that they were more often sleepy and tired during the day as compared to controls. But most strikingly, their sleep problems were not related to the severity of their visual impairment. Van Wijk: "These findings perfectly matched the reports of several parents of young USH2A patients, but that were never given a proper follow-up."

Hallmark feature of Usher syndrome
At a first glance, it may seem only a gradual difference, but the finding is much more significant. Van Wijk: "Actually, it means that the ubiquitously reported sleep problems by USH2A patients are not primarily due to impaired light perception, but that these problems already exist in patients who still have a near normal eyesight. Sleep problems should therefore probably be considered as an additional hallmark feature of Usher syndrome, and not as a consequence of poor or deteriorating eyesight." Of course, this conclusion based on questionnaires, needs further substantiation. This can be done, for example, through research in an existing zebrafish model for Usher syndrome. Zebrafish also have a distinct sleep pattern. Is it also disturbed? And is there evidence in the brain that Usher syndrome-associated proteins are somehow involved in regulating sleep? These research questions are currently being followed-up.

Improvement in quality of life
Van Wijk points out another aspect of the research. If sleep problems indeed turn out to be part of the disease, there might be a possibility to treat these problems. "Currently, sleep problems are not included in the daily care for Usher syndrome patients, because it is not yet being recognized as a hallmark feature of the disorder. As a result, the visit to a sleep clinic is often not reimbursed by health insurance companies. This hopefully changes based on the study published in Ophthalmology Science and the follow-up studies that are currently being conducted. Treatment of sleep problems will be a major step forward in improving the quality of life of Usher syndrome patients."
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Paper in Ophthalmology Science: Evaluation of sleep quality and fatigue in patients with Usher syndrome type 2a - Jessie M. Hendricks, MSc, Juriaan R. Metz, Hedwig M. Velde, Jack Weeda, Franca Hartgers, Suzanne Yzer, Carel B. Hoyng, Ronald J.E. Pennings, Rob W.J. Collin, H. Myrthe Boss, Erik de Vrieze, Erwin van Wijk

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