Kleine-Levin syndrome (Version 1.7)

NB. Clinical test guidance:
Imaging diagnostics refers to Brain MRI

Kleine-Levin syndrome and other inherited sleep disorders inclusion criteria (29583)
-Recurrent hypersomnia: 
-Recurrent episodes of excessive daytime sleepiness lasting for 2 days-4 weeks 
-Episodes recur at least once per year -Alertness, cognitive function and behavior are normal between episodes 
-Hypersomnia 
-AND at least 1 of the following: 
-Cognitive abnormalities 
– ex confusion, derealisation(“déjà vu” during episodes, dream-like state or experiencing out of body hallucinations 
-Abnormal behaviour – irritability, aggression 
-Hyperphagia 
OR 
-Recurrent daytime hypersomnia: 
-Sudden onset of sleep or "sleep attacks" 
-Other symptoms can include cataplexy, hypnagogic hallucinations and Sleep paralysis 
-A positive family history 
OR 
-Involuntary kicking and jerking movements of the legs and arms often repeated 100s of times during the night 
-Unaware of their multiple night-time awakenings unless they are witnessed by a bed partner 
-In extreme cases these brief arousals following the leg movements disturb sleep so much that they cause excessive daytime sleepiness 
-A +ve family history 
OR 
-The symptoms of parasomnias: 
-Sleepwalking—takes place during deep sleep, not REM sleep when dreams typically occur 
-Night terrors—these severe attacks cause people, usually children, to appear to wake up and scream in fear or panic 
-Sleep-eating disorders—these episodes occur during partial awakenings from deep sleep and cause individuals to eat without any knowledge of what they are doing. 
-A +ve family history Individuals with severe or syndromic disease should be recruited according to standard guidance, typically as trios. 
Disease status of apparently unaffected participants should be determined according to standard clinical practice to detect cryptic disease. In other cases, unaffected individuals should not be recruited. Recruitment in such families should favour multiplex families over single isolated cases. These singleton recruits will not contribute to the overall singleton monitoring metrics applied to GMCs.

Kleine-Levin syndrome and other inherited sleep disorders exclusion criteria (29583)
- No structural or inflammatory (MS-like) lesions on brain MRI.
- No atypical depression
- No sleep disorders (exclude Narcolepsy and Menstruation-related hypersomnia)
- No substance abuse (particularly benzodiazepine)
- No temporal lobe epilepsy
- Metabolic Encephalopathy
- Lyme disease
- Acute intermittent porphyria

Prior genetic testing guidance (29583)
- Results should have been reviewed for all genetic tests undertaken, including disease-relevant genes in exome sequencing data. The patient is not eligible if they have a molecular diagnosis for their condition. 
- Genetic testing should continue according to routine local practice for this phenotype regardless of recruitment to the project; results of these tests must be submitted via the ‘Genetic investigations’ section of the data capture tool to allow comparison of WGS with current standard testing.  

PLEASE NOTE: The sensitivity of WGS compared to current diagnostic genetic testing has not yet been established. It is therefore important that tests which are clinically indicated under local standard practice continue to be carried out.

Closing statement (29583)
These requirements will be kept under continual review during the main programme and may be subject to change.