Delineation of the adult phenotype of Coffin-Siris syndrome in 35 individuals

Hum Genet. 2024 Jan;143(1):71-84. doi: 10.1007/s00439-023-02622-5. Epub 2023 Dec 20.


Coffin-Siris syndrome (CSS) is a rare multisystemic autosomal dominant disorder. Since 2012, alterations in genes of the SWI/SNF complex were identified as the molecular basis of CSS, studying largely pediatric cohorts. Therefore, there is a lack of information on the phenotype in adulthood, particularly on the clinical outcome in adulthood and associated risks. In an international collaborative effort, data from 35 individuals ≥ 18 years with a molecularly ascertained CSS diagnosis (variants in ARID1B, ARID2, SMARCA4, SMARCB1, SMARCC2, SMARCE1, SOX11, BICRA) using a comprehensive questionnaire was collected. Our results indicate that overweight and obesity are frequent in adults with CSS. Visual impairment, scoliosis, and behavioral anomalies are more prevalent than in published pediatric or mixed cohorts. Cognitive outcomes range from profound intellectual disability (ID) to low normal IQ, with most individuals having moderate ID. The present study describes the first exclusively adult cohort of CSS individuals. We were able to delineate some features of CSS that develop over time and have therefore been underrepresented in previously reported largely pediatric cohorts, and provide recommendations for follow-up.

MeSH terms

  • Abnormalities, Multiple* / diagnosis
  • Abnormalities, Multiple* / genetics
  • Adult
  • Child
  • Chromosomal Proteins, Non-Histone / genetics
  • DNA Helicases / genetics
  • DNA-Binding Proteins / genetics
  • Face / abnormalities*
  • Hand Deformities, Congenital* / genetics
  • Humans
  • Intellectual Disability* / diagnosis
  • Intellectual Disability* / genetics
  • Micrognathism* / diagnosis
  • Micrognathism* / genetics
  • Neck / abnormalities
  • Nuclear Proteins / genetics
  • Phenotype
  • Transcription Factors / genetics


  • SMARCA4 protein, human
  • DNA Helicases
  • Nuclear Proteins
  • Transcription Factors
  • SMARCE1 protein, human
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • SMARCC2 protein, human

Supplementary concepts

  • Coffin-Siris syndrome