Hypersomnia in the Prader Willi syndrome: clinical-electrophysiological features and underlying factors.
OBJECTIVE
Excessive daytime sleepiness is a common symptom in Prader Willi syndrome (PWs). Sleep disordered breathing (SDB) and narcoleptic traits such as REM sleep onsets (SOREMPs) have been reported in these subjects. We evaluated nighttime and daytime sleep patterns in patients with PWs in order to clarify the nature of their hypersomnia.


METHODS
We performed overnight continuous EEG-polysomnographic studies (with breathing monitoring included) in 14 subjects (6 M,8 F; mean age 17 years, range 8-37) affected by PWs unselected for sleep disturbances. Ten patients underwent a Multiple Sleep Latency Test (MSLT) the day following the nocturnal sleep studies. Patients assessment was completed by means of immunogenetic characterization.


RESULTS
Nocturnal polysomnographic investigation documented sleep related breathing abnormalities such as central apneas, hypopneas or hypoventilation which mainly occurred during REM sleep in 8 subjects and did not cause sleep disruption. Only 4 subjects presented an increase in the Respiratory Disorder Index (RDI) slightly above the normal limits. In 8 subjects out of 10, with and without SDB, the mean daytime sleep latency could be considered abnormal according to the Tanner staging of pubertal development. Five patients showed at least two SOREMPs at MSLT. Subjects with and without SOREMPs had, respectively, a mean age of 18.6 SD 7.9 (4 M, 1 F) and 14.5 SD 2.9 (4 F, 1 M). The paternal deletion:uniparental dysomy ratio at genotypic characterization was 4:1 and 3.5:1 in subjects with and without SOREMPs, respectively. No patient presented DR-15 nor Dq-6.


CONCLUSIONS
Excessive sleepiness is a frequent disturbance in PWs. Subgroups of PW patients show hypersomnolence and SOREMPs. Sleep disordered breathing appears to have a limited role in the genesis of hypersomnia which not seems on the other hand attributable to the coexistence of narcolepsy phenotype. Hypersomnia in PW syndrome is likely to mainly be attributable to a primary hypothalamic dysfunction. The potential interacting role of other factors such as subjects age, sex and genetic pattern is suggested and deserve further investigation.
Manni
R
R
Centre of Sleep Medicine, IRCCS Institute of Neurology "C. Mondino", Via Palestro 3, 27100, Pavia, Italy.
Politini
L
L
Nobili
L
L
Ferrillo
F
F
Livieri
C
C
Veneselli
E
E
Biancheri
R
R
Martinetti
M
M
Tartara
A
A
D000293:Adolescent; D000328:Adult; D002648:Child; D002874:Chromosome Mapping; D002884:Chromosomes, Human, Pair 15; D002940:Circadian Rhythm / Q000502:physiology*; D006970:Disorders of Excessive Somnolence / Q000209:etiology / Q000235:genetics / Q000503:physiopathology*; D005260:Female; D018392:Genomic Imprinting; D005838:Genotype; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics; D015236:HLA-C Antigens / Q000235:genetics; D006683:HLA-DQ Antigens / Q000235:genetics; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D008285:Major Histocompatibility Complex; D008297:Male; D017286:Polysomnography; D011218:Prader-Willi Syndrome / Q000235:genetics / Q000276:immunology / Q000503:physiopathology*; D015656:Respiratory Mechanics; D012894:Sleep Stages / Q000502:physiology*; D014851:Wakefulness / Q000502:physiology
D015234:HLA-A Antigens; D015235:HLA-B Antigens; D015236:HLA-C Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens