Prevalence and Mimics of Kleine-Levin Syndrome: A Survey in French-Speaking Switzerland

Abstract

Study Objective: Kleine-Levin syndrome (KLS) is a rare disease of unknown etiology, the diagnosis of which can be challenging. We aimed to estimate KLS prevalence in French-speaking Switzerland, and assess differences with mimicking conditions. Methods: In this cross-sectional study, KLS patients were identified through a population-based approach, including at our hospital and contacting all sleepcertified facilities and neurologists in French-speaking Switzerland. Furthermore, we identified patients referred to our center for suspected KLS that received other diagnoses. Relevant clinical data of these two groups was compared. Results: We identified 7 patients with diagnosed KLS (6 since 2009), leading to a prevalence estimation of 3.19 per million (95% confidence interval: 1.55-6.59). Median age at diagnosis was 17 years (range: 12-19), 71.4% of them were men, and mean diagnosis delay after the first episode was 20.1 ± 10.9 months. We identified 9 mimic patients referred to our center; they differed from KLS patients by their higher age at disease onset (median: 15 [range: 12-16] vs. 19 [range: 16-64] years; p < 0.001), suspected KLS as referral reason (more frequent in mimics, p = 0.003), and the presence of precipitating factors (more frequent in KLS, p = 0.011). Among the mimic patients, 77% (versus 28% in KLS) had a psychiatric diagnosis. Conclusions: This study suggests a relatively higher KLS prevalence than previously reported. As compared to KLS, mimic patients have higher age at symptom onset, are more often initially referred for KLS suspicion, and have a higher prevalence of psychiatric disorders.

Kleine-Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci

“…Although most cases of KLS are sporadic, familial occurrence (3 to 8% of relatives) has been reported in studies (5,9), and there are reports of concordant twin pairs (9, 10) which, considering the rarity of the condition (a few cases per million individuals) (11), suggests genetic or shared environmental effects. Early studies had suggested a human leukocyte antigen (HLA) association suggestive of an autoimmune mechanism (12), but this was not confirmed in larger samples (3,8,13).…”

What respiratory physicians should know about narcolepsy and other hypersomnias

“…KLS is considered a markedly rare disease. Where examined, prevalence estimates range from 1.8 per million people in France [ 98 ] to 3.19 per million people in Switzerland [ 99 ]. It is not exclusive to a particular region, with documented cases throughout Europe, Asia, Africa and the Americas [ 100 , 101 ].…”

Kleine Levin syndrome is associated with birth difficulties and genetic variants in the TRANK1 gene loci

“…Each analysis used the 1000 genomes European dataset matched by principle components as a control cohort. The burden analyses were focused only in rare variants (minor allele counts [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] and restricted to predicted to be moderate or high modifiers as tagged by Annovar and SnpEff. Further, genes part of the rhythmic behavior pathway were collapsed, and SKAT based gene burden tests were performed (114) with resulting p-values adjusted using a 5% false discovery rate (FDR).…”

“…Although most cases of KLS are sporadic, familial occurrence (3-8% of relatives) has been reported in studies (5, 9) and there are reports of concordant twin pairs (9, 10)which, considering the rarity of the condition (a few cases per million individuals) (11), suggests genetic or shared environmental effects. Early studies had suggested an HLA association suggestive of an autoimmune mechanism (12), but this was not confirmed in larger samples (3, 8, 13).…”