Exploring the behavioral and cognitive phenotype of KBG syndrome

Genes Brain Behav. 2019 Apr;18(4):e12553. doi: 10.1111/gbb.12553. Epub 2019 Feb 21.


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.

Keywords: ANKRD11; KBG syndrome; attention; behavior; cognition; contextual neuropsychology; executive functioning; genetics; neurodevelopmental disorder; visuoconstruction.

MeSH terms

  • Abnormalities, Multiple / genetics
  • Abnormalities, Multiple / physiopathology*
  • Abnormalities, Multiple / psychology
  • Adolescent
  • Adult
  • Aged
  • Attention
  • Bone Diseases, Developmental / genetics
  • Bone Diseases, Developmental / physiopathology*
  • Bone Diseases, Developmental / psychology
  • Child
  • Cognition*
  • Executive Function
  • Facies
  • Female
  • Humans
  • Intellectual Disability / genetics
  • Intellectual Disability / physiopathology*
  • Intellectual Disability / psychology
  • Intelligence
  • Male
  • Memory
  • Middle Aged
  • Phenotype*
  • Repressor Proteins / genetics
  • Social Behavior
  • Tooth Abnormalities / genetics
  • Tooth Abnormalities / physiopathology*
  • Tooth Abnormalities / psychology
  • Visual Perception


  • ANKRD11 protein, human
  • Repressor Proteins

Supplementary concepts

  • KBG syndrome