Natural history of adults with KBG syndrome: A physician-reported experience

Genet Med. 2024 Aug;26(8):101170. doi: 10.1016/j.gim.2024.101170. Epub 2024 May 27.

Abstract

Purpose: KBG syndrome (KBGS) is a rare neurodevelopmental syndrome caused by haploinsufficiency of ANKRD11. The childhood phenotype is extensively reported but limited for adults. Thus, we aimed to delineate the clinical features of KBGS.

Methods: We collected physician-reported data of adults with molecularly confirmed KBGS through an international collaboration. Moreover, we undertook a systematic literature review to determine the scope of previously reported data.

Results: The international collaboration identified 36 adults from 31 unrelated families with KBGS. Symptoms included mild/borderline intellectual disability (n = 22); gross and/or fine motor difficulties (n = 15); psychiatric and behavioral comorbidities including aggression, anxiety, reduced attention span, and autistic features (n = 26); nonverbal (n = 3), seizures with various seizure types and treatment responses (n = 10); ophthalmological comorbidities (n = 20). Cognitive regression during adulthood was reported once. Infrequent features included dilatation of the ascending aorta (n = 2) and autoimmune conditions (n = 4). Education, work, and residence varied, and the diversity of professional and personal roles highlighted the range of abilities seen. The literature review identified 154 adults reported across the literature, and we have summarized the features across both data sets.

Conclusion: Our study sheds light on the long-term neurodevelopmental outcomes, seizures, behavioral and psychiatric features, and education, work, and living arrangements for adults with KBGS.

Keywords: ANKRD11; Adult; KBGS; Neurodevelopment; Seizure.

Publication types

  • Systematic Review

MeSH terms

  • Abnormalities, Multiple
  • Adolescent
  • Adult
  • Bone Diseases, Developmental
  • Facies
  • Female
  • Haploinsufficiency / genetics
  • Humans
  • Intellectual Disability* / epidemiology
  • Intellectual Disability* / genetics
  • Male
  • Middle Aged
  • Phenotype*
  • Physicians
  • Seizures / epidemiology
  • Seizures / genetics
  • Tooth Abnormalities
  • Young Adult

Supplementary concepts

  • KBG syndrome