June 2026 Research Update

This month added an early but more connected picture linking a possible clinical benefit with a specific brain mechanism in Kleefstra syndrome. In an international cohort, many of the people who tried olanzapine showed improvement in adaptive functioning (everyday skills), and supporting lab work pointed to overactive brain network signaling driven by astrocytes (support cells) as a possible target. Together, these results suggest olanzapine may help some people, and they also provide a concrete biological explanation that researchers can test further. [1]

In the clinical cohort of 54 people with Kleefstra syndrome, 16 were treated with olanzapine and 10 were reported to have improved adaptive functioning, while 4 had temporary improvement. The study did not report a comparison group, so it cannot show for sure how much change was due to the medication versus other factors, but it documents a notable pattern of reported functional change in routine care. This matters because adaptive functioning is closely tied to independence and day-to-day support needs. [1]

The same research team also studied human cell models and mouse brain tissue to understand what might be happening biologically. They observed neuronal hyperactivity (overactive signaling) linked to higher levels of S100B (a protein made by astrocytes), and this hyperactivity was reversed by olanzapine; lowering S100B also rescued the hyperactivity. This does not prove the same mechanism explains every person who improves, but it narrows the search to a specific pathway that future studies can measure and possibly use to identify who is more likely to respond. [1]

For families, this month provided both a real-world report of improved everyday functioning in some people taking olanzapine and a lab-based explanation that could be checked in future patient studies. The evidence is still exploratory because only 16 people received the drug and there was no direct comparison group, and the biology work was done in models rather than in living patients. What became clearer is the idea that a measurable signal (S100B-related overactivity in brain networks) may connect to symptoms and could eventually help researchers design better studies or identify subgroups, but it is not yet a proven test or a guaranteed predictor of benefit. [1]

This month highlighted two practical parts of living with rare genetic conditions: getting to a firm diagnosis and understanding common everyday difficulties like sleep. One study suggested a blood test that reads DNA methylation patterns can sometimes point to a specific syndrome (including Kleefstra syndrome), which may shorten a long diagnostic search when genetic testing is hard to access. Another study showed that sleep difficulties are elevated across many rare syndromes and tend to go along with challenges such as anxiety, autistic traits, hyperactivity/impulsivity, and more severe epilepsy. [2] [3]

In a small group of 19 patients with suspected genetic syndromes in the Dutch Caribbean, the EpiSign episignature assay found a positive match in 6 people, and these results were later confirmed as specific diagnoses that included Kleefstra syndrome 1. The study presents this as a model for a first step in diagnosis, especially where broad sequencing is limited, but it also notes the yield is preliminary and not every person will get an answer from this type of test. For families, the main message is that DNA pattern testing is being studied as another way to reach a clearer name for a condition in some cases. [2]

In a caregiver survey of 251 children with rare genetic syndromes (including Kleefstra syndrome), sleep problems such as night wakings, bedtime resistance, breathing-related sleep issues, parasomnias, and difficulty with sleep duration were reported more often than in typically developing children. The study also found that higher levels of sleep difficulty went along with higher anxiety and depressed mood, more autism-related traits, more overactivity/impulsivity, more severe epilepsy, and more severe physical health conditions, with socioeconomic status also linked. This helps place sleep issues in a broader context: they may cluster with other day-to-day challenges rather than being an isolated problem. [3]

For patients and caregivers, these studies mainly add understanding rather than changing care right now. The diagnostic study suggests that a blood-based DNA methylation test may help some people get a more definite diagnosis, including Kleefstra syndrome, but it was small and it will not work for everyone. The sleep study helps clarify that sleep difficulties are common across rare genetic syndromes and tend to occur alongside emotional, behavioral, and seizure-related challenges, which may help families and researchers talk about sleep as part of the overall health picture. What remains uncertain is how well these findings apply to every person with Kleefstra syndrome specifically, since the sleep study grouped multiple syndromes together and relied on caregiver reports. [2] [3]