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

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.

Automated summary

Heterozygous disease-causing variants in BCL11B are responsible for a rare neurodevelopmental syndrome involving craniofacial and immunological abnormalities. We report three new cases with de novo heterozygous frameshift variants in exon 4 of BCL11B, all presenting with developmental delay, recurrent infections, facial dysmorphism, and variable degrees of craniosynostosis. This study expands the knowledge of genotypes and phenotypes associated with BCL11B-related BAFopathy and provides insights into the clinical and genomic spectrum of this disorder.