Further validation of craniosynostosis as a part of phenotypic spectrum of BCL11B-related BAFopathy

Am J Med Genet A. 2023 Aug;191(8):2175-2180. doi: 10.1002/ajmg.a.63330. Epub 2023 Jun 20.


Heterozygous disease-causing variants in BCL11B are the basis of a rare neurodevelopmental syndrome with craniofacial and immunological involvement. Isolated craniosynostosis, without systemic or immunological findings, has been reported in one of the 17 individuals reported with this disorder till date. We report three additional individuals harboring de novo heterozygous frameshift variants, all lying in the exon 4 of BCL11B. All three individuals presented with the common findings of this disorder i.e. developmental delay, recurrent infections with immunologic abnormalities and facial dysmorphism. Notably, craniosynostosis of variable degree was seen in all three individuals. We, thus add to the evolving genotypes and phenotypes of BCL11B-related BAFopathy and also review the clinical, genomic spectrum along with the underlying disease mechanisms of this disorder.

Keywords: BAFopathy; BCL11B; craniosynostosis; immunodeficiency; neurodevelopment; transcription factor.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Craniosynostoses* / diagnosis
  • Craniosynostoses* / genetics
  • Frameshift Mutation
  • Humans
  • Intellectual Disability* / genetics
  • Neurodevelopmental Disorders* / genetics
  • Phenotype
  • Repressor Proteins / genetics
  • Transcription Factors / genetics
  • Tumor Suppressor Proteins / genetics


  • Transcription Factors
  • Tumor Suppressor Proteins
  • BCL11B protein, human
  • Repressor Proteins