Wenz Elena, Tafti Mehdi, Bassetti Claudio L A
Department of Neurology, Inselspital, University Hospital of Bern, University of Bern, Switzerland; Graduate School for Health Sciences, University of Bern, Switzerland.
Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.
Sleep Med. 2022 Mar;91:105-108. doi: 10.1016/j.sleep.2022.02.019. Epub 2022 Feb 28.
Kleine-Levin syndrome (KLS) is a rare and debilitating disorder presenting with periodic hypersomnolence, cognitive, psychiatric and behavioral disturbances. In the absence of biomarkers it can be difficult to diagnose. Rare LMOD3 variants in a family and in seven sporadic cases with KLS have been described. Here we report a patient and her family with an unclassified, familial, periodic central disorder of hypersomnolence (CDH) in whom the presence of a LMOD3 gene variant was assessed.
The female patient presented since early adulthood with recurrent episodes of hypersomnolence. Over more than 20 years of follow-up the diagnoses of idiopathic hypersomnia, KLS and hypersomnia associated with a psychiatric condition were made. The family history is positive for periodic hypersomnolence and psychiatric conditions. The patient, her symptomatic mother and her asymptomatic sister carried a Proline for Histidine substitution at codon 552 of the LMOD3-gene. This variant was previously reported in two sporadic KLS patients and its frequency in the general population is below 0.02%.
We report the association of periodic hypersomnia with a polymorphism of the LMOD3-gene in a patient with atypical KLS and a positive family history. Further research is needed to assess the pathological and predictive value of LMOD3 variants in KLS.
克莱恩-莱文综合征（KLS）是一种罕见且使人衰弱的疾病，表现为周期性嗜睡、认知、精神和行为障碍。在缺乏生物标志物的情况下，可能难以诊断。已有报道称在一个家族和7例散发性KLS病例中存在罕见的LMOD3基因变异。在此，我们报告一名患者及其家族，他们患有未分类的家族性周期性中枢性嗜睡障碍（CDH），并对其中LMOD3基因变异的存在情况进行了评估。
该女性患者自成年早期起就出现反复发作的嗜睡症状。在超过20年的随访中，曾被诊断为特发性嗜睡症、KLS以及与精神疾病相关的嗜睡症。家族史显示有周期性嗜睡和精神疾病。该患者、其有症状的母亲和无症状的妹妹在LMOD3基因的第552密码子处存在脯氨酸被组氨酸替代的情况。此变异先前在两名散发性KLS患者中被报道过，其在普通人群中的频率低于0.02%。
我们报告了一名非典型KLS且家族史呈阳性的患者中周期性嗜睡与LMOD3基因多态性之间的关联。需要进一步研究以评估LMOD₃基因变异在KLS中的病理和预测价值。
