Clinical and Neurodevelopmental Course in a Case of EFNB1-Related Craniofrontonasal Syndrome With Unrepaired...

Craniofrontonasal syndrome displays an unusual X-linked dominant inheritance pattern due to pathogenic variants in EFNB1, which encodes a membrane-bound ligand for the ephrin receptor. Females exhibit a more severe phenotype than males and can have craniosynostosis, hypertelorism, craniofacial asymmetry, thoracic skeleton abnormalities, and an assortment of other features. Males typically only develop a milder hypertelorism, or they have no discernable features at all.

Exome sequencing was used to identify a likely pathogenic EFNB1 c.129-2A>G splice site variant in an individual who had facial dysmorphology.

We describe a 14-year-old female from an underserved Caribbean population who had facial dysmorphology, microcephaly, and mild intellectual disability. She also had an uncorrected craniosynostosis that was diagnosed during clinical examination.

The craniofrontonasal syndrome in the individual presented in this report is explained by the EFNB1 variant. The affected individual did not have surgical correction of her craniosynostosis, which might have contributed to her development of microcephaly and mild intellectual disability.