Mechanisms underlying the EEG biomarker in Dup15q syndrome.
Joel Frohlich, Lawrence T Reiter, Vidya Saravanapandian and 10 others
PMID 31312421WHAT IT FOUND
Children with Dup15q syndrome had higher beta-band EEG power than typically developing children, and midazolam produced a similar beta rise in adults.
Two children with paternal Dup15q also showed the pattern.
Key findings
01Children with Dup15q syndrome had higher EEG power than typically developing children in the 20.2-28.5 Hz beta range.
02Midazolam increased beta power in central scalp regions, with average change peaking at 23.0 Hz, close to the Dup15q beta peak.
03Both paternal Dup15q cases showed beta EEG phenotypes, suggesting UBE3A overexpression alone is not necessary.
STILL TO COME
How it was doneWhat they found
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What it does not show
The Dup15q sample is small, with 27 children analysed, so the findings may not apply broadly. Only two maternal parent-of-origin cases were confirmed in the reference cohort, so the assumed maternal composition is not fully verified. The midazolam group was healthy adults, not children, and EEG systems differed from the Dup15q cohorts, so the drug comparison is not a direct group match. The authors state that their conclusions are not formal inferences and do not prove the beta EEG phenotype is GABAergic. Only two paternal Dup15q cases were examined, so the UBE3A necessity finding rests on a very small group. Participants with epilepsy or medications affecting GABAergic transmission were excluded, and at least three participants later developed seizures, so the sample does not represent all Dup15q patients. UBE3A is expressed biallelically in astrocytes, which may make paternal Dup15q cases imperfect controls for UBE3A.
Declared interests
Funded by NIH, NIH/NIMH, Foundation for Prader-Willi Research, Dup15q Alliance, and Shainberg Neuroscience Fund. The midazolam data came from a Roche-sponsored trial (WP29393).
The easy way to misread this
Do not conclude from this paper that GABA-targeting treatment, EEG testing, or Dup15q-specific therapy has been shown to improve patient outcomes. The study describes a biomarker pattern, not a treatment effect, and the authors state that their mechanism conclusions are not formal inferences.