Kleine-Levin Syndrome (KLS) and other inherited sleep disorders

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

Inclusion criteria:

  • Recurrent hypersomnia:
    • Recurrent episodes of excessive daytime sleepiness lasting for 2 days to 4 weeks
    • Episodes recur at least once per year
    • Alertness, cognitive function and behavior are normal between episodes
    • Hypersomnia
  • AND at least one 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


  • Recurrent daytime hypersomnia:
    • Sudden onset of sleep, or “sleep attacks,”
    • Other symptoms can include cataplexy, hypnagogic hallucinations and Sleep paralysis
    • A positive family history


  • Involuntary kicking and jerking movements of the legs and arms, often repeated hundreds of times during the night
    • Unaware of their multiple night-time awakenings unless they are witnessed by a bed
    • In extreme cases, these brief arousals following the leg movements disturb sleep so much that they cause excessive daytime
    • A positive family history


  • The symptoms of parasomnias:
    • Sleepwalking—takes place during deep sleep (not REM sleep, when dreams typically
    • Night terrors—these severe attacks cause people, usually children, to appear to wake up and scream in fear or
    • Sleep-eating disorders—these episodes, occur during partial awakenings from deep sleep and cause individuals to eat without any knowledge of what they are
    • A positive 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.

Exclusion criteria:

  • No structural or inflammatory (MS-like) lesions on brain
  • No atypical depression
  • No substance abuse (particularly benzodiazepine)
  • No temporal lobe epilepsy
  • Metabolic Encephalopathy
  • Lyme disease
  • Acute intermittent porphyria

Prior genetic testing guidance 

  • 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 

These requirements will be kept under continual review during the main programme and may be subject to change.

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