The Kleine-Levin hibernation syndrome is a rare disorder that occurs predominantly in males and is characterized by episodic attacks of aberrant behavior, hypersomnia, and increased feeding (megaphagia) and sex drives (Kleine, 1925; Levin, 1929).
Popper et al. (1980) described a Hawaiian Caucasian kindred in which at least 9 members showed this syndrome. Episodic hypersomnolence was associated with disorientation, vivid hallucinations, compulsive hyperphagia, and erotic behavior. Affected persons were entirely normal between attacks. ... Popper et al. (1980) described a Hawaiian Caucasian kindred in which at least 9 members showed this syndrome. Episodic hypersomnolence was associated with disorientation, vivid hallucinations, compulsive hyperphagia, and erotic behavior. Affected persons were entirely normal between attacks. Five males and 4 females were affected. Three would-be heterozygotes denied attacks. Katz and Ropper (2002) reported an affected brother and sister. A 15-year-old boy developed flu-like symptoms without fever. For 9 days, he remained in bed, slept excessively, and when awake, frequently requested unusual (for him) salty food, finishing whatever amount he was given. During the following 10 months, he had 8 similar episodes of hypersomnia lasting between 7 and 12 days. Throughout the following 5 years, he continued to have spells intermittently, with lessening frequency but of longer duration (as long as 81 days). In 5 years, he had 16 spells. Often, attacks were immediately preceded by stress or slight alcohol consumption. While affected, the patient was observed to be in a light sleep for much of the day, frequently shifting positions and remaining easily arousable. Between spells he was animated and articulate, with normal social behavior, functioning at a high level in college, and maintaining normal peer relationships. The sister reported by Katz and Ropper (2002) began having hypersomnolent spells at age 13 years, with the first preceded by a brief flu-like illness. During episodes, she spent as many as 20 hours per day in bed sleeping or physically inactive. When awake, she was irritable and withdrawn. Her behavior and personal account of her mental state during the spells were essentially identical to her brother's. They had not, however, discussed their experiences extensively. In the next 5 years, she had 18 spells, 1 of them as long as 72 days. She described the spells as 'a persistent sense of unreality and disconnection' from her environment. Numerous medications were ineffective in either preventing or reducing the duration of the spells in either patient. Hypocretin (602358) was present in normal levels in the spinal fluid of 1 of the sibs reported by Katz and Ropper (2002). Huang et al. (2008) reported polysomnographic features in 19 Taiwanese patients with Kleine-Levin syndrome. Studies performed before the end of the first half of the symptomatic period showed a reduction in slow wave sleep with progressive return to normal during the second half, despite persistence of clinical symptoms. REM sleep remained normal in the first half of the episode, but decreased in the second half: the differences between first and second half of episodes were significant for slow wave sleep (p = 0.014) and REM sleep (p = 0.027). The overall mean sleep latency was 9.51 minutes, and 7 of 17 patients had 2 or more sleep onset REM periods during the symptomatic period. Huang et al. (2008) concluded that important changes in sleep occur over time during the symptomatic period, but latency studies do not correlate with symptom onset. Arnulf et al. (2008) reviewed the clinical features of 108 patients with Kleine-Levin syndrome. The group mostly consisted of adolescent boys (76%), and the mean age at onset was 15.7 years. There was an unexpected high frequency of Ashkenazi Jewish individuals. During episodes, most patients reported overall apathy, exhaustion, and dramatically increased sleep, although some reported irritability and aggression. The most common specific symptoms during episodes included sleep 'drunkenness,' (83%) with difficulty awakening and intense dreaming, hyperphagia (66%), hypersexuality (53%), impaired speech (94%) and concentration (91%), fever (68%), altered perception as in a dream state (81%), and psychologic changes (87%) such as irritability, frustration, and depressed mood. All reported restoration of normal function between episodes, with behavior similar to controls, except that patients tended to have a higher body mass index (BMI). The disorder lasted a median of 13.6 years. Personal history revealed that 25% of patients had problems at birth, such as long labor or hypoxia, and 15% had delayed speech, walking, or reading, which was increased compared to controls. There were 5 multiplex families. HLA-DR and HLA-DQ alleles did not differ between patients and controls. Some therapeutic response to amantadine was observed. Overall, patients averaged 19 episodes of a mean of 12.5 days, totaling more than 8 months of incapacitation over 14 years. These findings indicated that the disorder is not as benign as sometimes perceived.
The sibs reported by Katz and Ropper (2002) shared the HLA-DR2 and -DQ1 antigens.
In 30 unrelated patients with Kleine-Levin syndrome, Dauvilliers et al. (2002) found an increased frequency of the HLA-DQB1*0201 allele (see 604305) (28.3% ... The sibs reported by Katz and Ropper (2002) shared the HLA-DR2 and -DQ1 antigens. In 30 unrelated patients with Kleine-Levin syndrome, Dauvilliers et al. (2002) found an increased frequency of the HLA-DQB1*0201 allele (see 604305) (28.3% vs 12.5% in controls). One subject and his affected mother were DQB1*0201 homozygous.