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.
Sarah Leigh (Genomics England Curator)
Group: Other
Workplace: Other
Rosa Peraita-Adrados (Sleep and Epilepsy Unit-Clinical Neurophysiology Service. Gregorio Maranon University Hospital. Complutense University of Madrid (UCM).Madrid.Spain.)
Group: Other NHS organisation
Workplace: NHS clinical service
Louise Daugherty (Genomics England Curator)
Group: Other
Workplace: Other
Eleanor Williams (Genomics England Curator)
Group: Other
Workplace: Other
List | Entity | Reviews | Mode of inheritance | Details | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Green List (high evidence) |
DNMT1 |
2 reviews |
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown |
Sources
Phenotypes
Tags |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Amber List (moderate evidence) |
CSNK1D |
1 review |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Amber List (moderate evidence) |
MOG |
2 reviews1 green |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Red List (low evidence) |
AKR1C2 |
1 review |
Unknown |
Sources
Phenotypes
Tags |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Red List (low evidence) |
CRY1 |
1 review1 red |
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown |
Sources
Phenotypes
Tags |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Red List (low evidence) |
EIF3G |
1 review1 red |
Unknown |
Sources
Phenotypes
Tags |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Red List (low evidence) |
EXT1 |
2 reviews |
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown |
Sources
Phenotypes
Tags |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Red List (low evidence) |
HCRT |
1 review |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Red List (low evidence) |
HLA-DQB1 |
1 review |
Unknown |
Sources
Phenotypes
Tags |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Red List (low evidence) |
NTRK2 |
1 review |
Unknown |
Sources
Phenotypes
Tags |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Red List (low evidence) |
PER2 |
1 review |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Red List (low evidence) |
SLC6A4 |
1 review |
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown |
Sources
Phenotypes
Tags |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Red List (low evidence) |
TRPV4 |
3 reviews1 red |
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted |
Sources
Phenotypes
Tags |
Rosa Peraita-Adrados (Sleep and Epilepsy Unit-Clinical Neurophysiology Service. Gregorio Maranon University Hospital. Complutense University of Madrid (UCM).Madrid.Spain.), agrees with the status of the gene on this panel, although she has not reviewed every gene individually