University of North Carolina School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA.
McKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Am J Med Genet A. 2022 Oct;188(10):3041-3048. doi: 10.1002/ajmg.a.62921. Epub 2022 Aug 5.
Kabuki syndrome (KS) is a rare epigenetic disorder caused by heterozygous loss of function variants in either KMT2D (90%) or KDM6A (10%), both involved in regulation of histone methylation. While sleep disturbance in other Mendelian disorders of the epigenetic machinery has been reported, no study has been conducted on sleep in KS. This study assessed sleep in 59 participants with KS using a validated sleep questionnaire. Participants ranged in age from 4 to 43 years old with 86% of participants having a pathogenic variant in KMT2D. In addition, data on adaptive function, behavior, anxiety, and quality of life were collected using their respective questionnaires. Some form of sleep issue was present in 71% of participants, with night-waking, daytime sleepiness, and sleep onset delay being the most prevalent. Sleep dysfunction was positively correlated with maladaptive behaviors, anxiety levels, and decreasing quality of life. Sleep issues were not correlated with adaptive function. This study establishes sleep disturbance as a common feature of KS. Quantitative sleep measures may be a useful outcome measure for clinical trials in KS. Further, clinicians caring for those with KS should consider sleep dysfunction as an important feature that impacts overall health and well being in these patients.
歌舞伎综合征(KS)是一种罕见的表观遗传疾病,由 KMT2D(90%)或 KDM6A(10%)中的杂合功能丧失变异引起,这两者都参与组蛋白甲基化的调节。虽然已经报道了其他表观遗传机制的孟德尔疾病中的睡眠障碍,但尚未对 KS 中的睡眠进行研究。本研究使用经过验证的睡眠问卷评估了 59 名 KS 参与者的睡眠情况。参与者的年龄从 4 岁到 43 岁不等,86%的参与者在 KMT2D 中存在致病性变异。此外,还使用各自的问卷收集了适应功能、行为、焦虑和生活质量的数据。71%的参与者存在某种形式的睡眠问题,最常见的是夜间醒来、白天嗜睡和入睡延迟。睡眠功能障碍与适应不良行为、焦虑水平和生活质量下降呈正相关。睡眠问题与适应功能无关。本研究确立了睡眠障碍是 KS 的一个常见特征。定量睡眠测量可能是 KS 临床试验的有用结果测量指标。此外,照顾 KS 患者的临床医生应将睡眠功能障碍视为影响这些患者整体健康和幸福感的重要特征。