Assessment & Research

Molecularly confirmed Kabuki (Niikawa-Kuroki) syndrome patients demonstrate a specific cognitive profile with extensive visuospatial abnormalities.

Harris et al. (2019) · Journal of intellectual disability research : JIDR 2019
★ The Verdict

Kabuki syndrome shows a sharp visuospatial drop that sets it apart from other ID causes.

✓ Read this if BCBAs assessing kids with rare genetic syndromes in clinic or school.
✗ Skip if Practitioners serving only ASD or ADHD with no rare-syndrome caseload.

01Research in Context

01

What this study did

The team tested kids with Kabuki syndrome and kids with other intellectual disabilities. Both groups had the same IQ range so the test was fair.

They gave puzzles that use eyes and hands together. The tasks showed how well each child could judge space, copy shapes, and find hidden pictures.

02

What they found

Kabuki kids scored far lower on visuospatial tasks than IQ-matched peers. Their sentence understanding was only a little better, not enough to matter day-to-day.

The gap was big enough to act like a fingerprint. Future drug or training trials can use this gap as a clear target.

03

How this fits with other research

Mulder et al. (2020) also used visuospatial puzzles in Williams syndrome. They found a left-side bias, while Kabuki kids showed wide visuospatial weakness. The two syndromes now have distinct visual markers.

de Leeuw et al. (2024) tracked eye movements to separate cerebral visual impairment from ADHD. Like the Kabuki study, they proved that a short visual test can tell one diagnosis from another.

Miezah et al. (2020) warn that Williams profiles vary a lot. The Kabuki paper adds a second rare syndrome with its own tight pattern, so clinicians should test, not assume.

04

Why it matters

If you work with rare genetic disorders, add a quick visuospatial battery to your assessment. A low score next to fair language can flag Kabuki, guide referrals, and give you a baseline for skill-building programs.

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Add a shape-copy or block-design subtest to your intake; note large visuospatial-language gap as a Kabuki red flag.

02At a glance

Intervention
not applicable
Design
quasi experimental
Sample size
44
Population
intellectual disability, other
Finding
mixed
Magnitude
large

03Original abstract

BACKGROUND: Kabuki (Niikawa-Kuroki) syndrome (KS) is caused by disease-causing variants in either of two components (KMT2D and KDM6A) of the histone methylation machinery. Nearly all individuals with KS have cognitive difficulties, and most have intellectual disability. Recent studies on a mouse model of KS suggest disruption of normal adult neurogenesis in the granule cell layer of the dentate gyrus of the hippocampus. These mutant mice also demonstrate hippocampal memory defects compared with littermates, but this phenotype is rescued postnatally with agents that target the epigenetic machinery. If these findings are relevant to humans with KS, we would expect significant and disproportionate disruption of visuospatial functioning in these individuals. METHODS: To test this hypothesis, we have compiled a battery to robustly explore visuospatial function. We prospectively recruited 22 patients with molecularly confirmed KS and 22 IQ-matched patients with intellectual disability. RESULTS: We observed significant deficiencies in visual motor, visual perception and visual motor memory in the KS group compared with the IQ-matched group on several measures. In contrast, language function appeared to be marginally better in the KS group compared with the IQ-matched group in a sentence comprehension task. CONCLUSIONS: Together, our data suggest specific disruption of visuospatial function, likely linked to the dentate gyrus, in individuals with KS and provide the groundwork for a novel and specific outcome measure for a clinical trial in a KS population.

Journal of intellectual disability research : JIDR, 2019 · doi:10.1111/jir.12596