Exploring the behavioral and cognitive phenotype of KBG syndrome
Open accessAbstract
KBG syndrome is a neurodevelopmental disorder, caused by dominant mutations in ANKRD11, that is characterized by developmental delay/intellectual disability, mild craniofacial dysmorphisms, and short stature. Behavior and cognition have hardly been studied, but anecdotal evidence suggests higher frequencies of ADHD‐symptoms and social‐emotional impairments. In this study, the behavioral and cognitive profile of KBG syndrome will be investigated in order to examine if and how cognitive deficits contribute to behavioral difficulties. A total of 18 patients with KBG syndrome and a control group consisting of 17 patients with other genetic disorders with comparable intelligence levels, completed neuropsychological assessment. Age‐appropriate tasks were selected, covering overall intelligence, attention, memory, executive functioning, social cognition and visuoconstruction. Results were compared using Cohen's d effect sizes. As to behavior, fewer difficulties in social functioning and slightly more attentional problems, hyperactivity, oppositional defiant behavior and conduct problems were found in the KBG syndrome group. Regarding cognitive functioning, inspection of the observed differences shows that patients with KBG syndrome showed lower scores on sustained attention, cognitive flexibility, and visuoconstruction. In contrast, the KBG syndrome group demonstrated higher scores on visual memory, social cognition and emotion recognition. The cognitive profile of KBG syndrome in this sample indicates problems in attention and executive functioning that may underlie the behavior profile which primarily comprises impulsive behavior. Contrary to expectations based on previous (case) reports, no deficits were found in social cognitive functioning. These findings are important for counseling purposes, for tailored education planning, and for the development of personalized intervention.
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Other monogenic syndromes like Kleefstra, KBG, WitKoS, Angelman, Coffin-Sirris, Rubinstein-Taybi, Phelan-McDermid, Smith-Magenis Syndrome and Kabuki syndrome also have a clear prefrontal component in their behavioral and cognitive phenotype.
“Other monogenic syndromes like Kleefstra, KBG, WitKoS, Angelman, Coffin-Sirris, Rubinstein-Taybi, Phelan-McDermid, Smith–Magenis Syndrome and Kabuki syndrome also have a clear prefrontal component in their behavioral and cognitive phenotype [272–280].”
From Development of prefrontal cortex (2022) · cites this paper as [273]
For KBG syndrome, the Discussion reports difficulties with sustained attention, inhibition and cognitive flexibility, alongside impulsive behavior. These findings support a behavioral and cognitive component consistent with the citing sentence, but the paper does not establish that it is specifically prefrontal; it also does not study the other listed syndromes. (LLM, conf=0.82)
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Development of prefrontal cortex
Kolk, S. M., & Rakic, P. (2022) · Neuropsychopharmacology · doi:10.1038/s41386-021-01137-9 · Cited by 378 · see citing works
- Authors
- van Dongen, L. C. M., Wingbermühle, E., van der Veld, W. M., Vermeulen, K., Bos‐Roubos, A. G., Ockeloen, C. W., Kleefstra, T., & Egger, J. I. M.
- Affiliations
- Centre of Excellence for Neuropsychiatry Vincent van Gogh Institute for Psychiatry Venray The Netherlands
- Radboud University Nijmegen (NL)
- Behavioral Science Institute Radboud University Nijmegen Nijmegen The Netherlands
- Radboud University Medical Center (NL)
- ORCID
- Venue
- Genes, Brain and Behavior
- Publisher
- Wiley
- Published
- 2019-02-21
- Volume
- 18
- Issue
- 4
- Pages
- e12553-e12553
- ISSN
- 1601-183X (ISSN-L)
- 1601-1848
- PMC
- PMC6850621
- OpenAlex
- W2915285389
- Cited by
- 20
- References
- 21
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 1 · 2022: 2 · 2021: 6 · 2020: 2 · 2019: 1
- FWCI
- 1.66
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Genes Brain & Behavior (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion, other-oa)
- Funders
- Radboud Universiteit
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Keywords
- KBG syndrome, ANKRD11, neurodevelopmental disorders, intellectual disability, behavioral phenotypes, cognitive profile, attention deficits, executive function, social cognition, visuoconstruction, ADHD symptoms, oppositional defiant behavior, conduct problems, hyperactivity, emotion recognition, genetic counseling
- MeSH terms
- Abnormalities, Multiple, Adolescent, Adult, Aged, Attention, Bone Diseases, Developmental, Child, Cognition, Female, Humans, Intelligence, Male, Memory, Intellectual Disability, Middle Aged, Phenotype, Repressor Proteins, Social Behavior, Tooth Abnormalities, Visual Perception, Facies, Executive Function
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