Genetic subtype may affect duration of low oxygen in Prader-Willi syndrome
Deletion group spent longer with low oxygen than maternal UPD group
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The duration of low blood oxygen levels during sleep may vary among people with Prader-Willi syndrome (PWS) depending on their genetic subtype, a small study in Brazil suggests.
Researchers found that children and young adults with PWS caused by a genetic deletion — the most common PWS cause — spent significantly more time with low blood oxygen levels during overnight sleep testing than those with the second most common genetic cause, called maternal uniparental disomy.
The difference emerged even though other sleep-related breathing measures, including how often breathing stopped or became shallow during sleep, did not differ significantly across groups.
Study points to possible genetic differences in sleep breathing
“These preliminary findings suggest [genetic subtype-specific] sleep respiratory profiles in PWS that merit investigation in larger, [studies following patients over time],” the researchers wrote.
The observational, cross-sectional study, “Sleep respiratory profiles across genetic subtypes of Prader-Willi syndrome: an exploratory polysomnographic study,” was published in Sleep Epidemiology.
People typically have 23 pairs of chromosomes, threadlike structures where genes sit, with one copy of each pair inherited from each parent. PWS results when genes in a specific region of chromosome 15, called the PWS locus, that normally are active on the paternal copy are missing or switched off. The corresponding genes inherited from the mother are normally inactive.
In most cases, the disease arises due to a paternal genetic deletion, meaning the PWS locus inherited from the father is missing. In others, the disease is caused by maternal uniparental disomy, meaning the individual inherits two copies of chromosome 15 from the mother and none from the father. More rarely, an imprinting defect causes the paternal genes of the PWS locus to be mistakenly silenced.
Sleep problems are common PWS symptoms. These can include excessive daytime sleepiness and sleep-related breathing issues, particularly obstructive sleep apnea, in which the upper airway repeatedly becomes blocked during sleep.
Several PWS-related features may contribute to sleep-related breathing problems, including obesity, low muscle tone, and differences in facial and airway structures.
“Although there is evidence that clinical features of PWS are associated with its genetic subtypes … regarding sleep symptoms, specifically respiratory sleep symptoms, there still is a scarcity of data,” the researchers wrote.
Researchers compare sleep across 3 PWS genetic subtypes
To learn more, a team of researchers analyzed sleep and sleep-related breathing patterns in 53 people with PWS who underwent polysomnography at a specialized sleep clinic within the Children’s Institute of the University of São Paulo Medical School, in Brazil.
Polysomnography is an overnight test that monitors breathing, oxygen levels, brain activity, and other body functions during sleep.
Participants had a mean age of 9.96 years, ranging from 2 to 22. Among them, 28 (52.8%) had a paternal genetic deletion, 19 (35.8%) had maternal uniparental disomy, and six (11.3%) had an imprinting defect.
Age, sex distribution, and body mass index (BMI), a measure of weight relative to height used as a proxy of body fat, did not differ significantly across groups.
The researchers found that oxygen saturation, a measure of oxygen levels in the blood, was below 90% for a significantly longer total time during the overnight recording in the genetic deletion group compared with the maternal uniparental disomy group (mean, 64.27 vs. 10.66 minutes).
The imprinting defect group had the highest mean total time with oxygen saturation below 90%, at 80.6 minutes, but results varied widely among the six participants with this genetic defect. There were no significant differences between this group and the other two groups for this measure.
Other breathing measures were similar across genetic groups
Other breathing measures did not differ significantly across groups. These included the lowest oxygen saturation level recorded, the apnea-hypopnea index — which measures how often breathing stops or becomes shallow per hour of sleep — and the obstructive apnea index, which measures how many blocked-airway breathing events occur per hour of sleep.
The findings suggest that the duration of low oxygen may reveal differences that are less apparent when counting breathing interruptions alone.
In addition, participants with a paternal genetic deletion slept significantly less than those with an imprinting defect (mean of about 6.5 hours vs. about 7.5 hours).
Exploratory post-hoc analyses of small subgroups suggested that, within the deletion group, obesity was associated with more breathing interruptions during sleep, longer periods of low oxygen, and lower minimum oxygen levels. The researchers cautioned that these findings were preliminary and require confirmation in larger studies.
“These findings support the hypothesis that PWS genetic subtype may influence sleep respiratory [features] and highlight the need for prospective, multicenter studies with larger [patient populations] to characterize [genetic subtype-specific sleep] trajectories and inform clinical monitoring strategies,” the researchers wrote.
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