Extending the clinical and genetic spectrum of ARID2 related intellectual disability. A case series of 7 patients

Eur J Med Genet. 2019 Jan;62(1):27-34. doi: 10.1016/j.ejmg.2018.04.014. Epub 2018 Apr 23.


In the last 3 years de novo sequence variants in the ARID2 (AT-rich interaction domain 2) gene, a subunit of the SWI/SNF complex, have been linked to intellectual disabilities in 3 case reports including one which describes frameshift mutations in ARID2 in 2 patients with features resembling Coffin-Siris syndrome. Coffin-Siris syndrome (CSS) is a rare congenital syndrome characterized by intellectual deficit, coarse facial features and hypoplastic or absent fifth fingernails and/or toenails among other features. Mutations in a number of different genes encoding SWI/SNF chromatin remodelling complex proteins have been described but the underlying molecular cause remains unknown in approximately 40% of patients with CSS. Here we describe 7 unrelated individuals, 2 with deletions of the ARID2 region and 5 with de novo truncating mutations in the ARID2 gene. Similarities to CSS are evident. Although hypertrichosis and hypoplasia of the fifth finger nail and distal phalanx do not appear to be common in these patients, toenail hypoplasia and the presence of Wormian bones might support the involvement of ARID2.

Keywords: ARID2; Coffin-siris syndrome; DDD study; Genetic association; Intellectual disability.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / pathology
  • Adolescent
  • Child
  • Child, Preschool
  • Face / abnormalities*
  • Face / pathology
  • Female
  • Hand Deformities, Congenital / genetics*
  • Hand Deformities, Congenital / pathology
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Male
  • Micrognathism / genetics*
  • Micrognathism / pathology
  • Neck / abnormalities*
  • Neck / pathology
  • Phenotype*
  • Transcription Factors / genetics*


  • ARID2 protein, human
  • Transcription Factors

Supplementary concepts

  • Coffin-Siris syndrome