Second family with the boston-type craniosynostosis syndrome: Novel mutation and expansion of the clinical spectrum

Craniosynostosis, caused by early fusion of one or more cranial sutures, can affect the coronal or lambdoid sutures, or include premature fusion of the sagittal (scaphocephaly) or metopic suture (trigonocephaly). Often occurring as isolated finding, their co‐existence in a craniosynostosis syndrome is infrequent. We describe a four‐generation family with variable expression of a craniosynostosis phenotype with scaphocephaly and a particularly severe trigonocephaly. Molecular analysis revealed a missense mutation in the MSX2—associated with the Boston‐type craniosynostosis syndrome—affecting the same amino‐acid residue as in the original Boston family. Besides unique features such as the cranial sutures involved, minor limb abnormalities and incomplete penetrance, our patients share with the original family autosomal dominant inheritance and the presence of multiple endocranial erosions on CT imaging. Though these findings appear to be important diagnostic clues for MSX2‐related craniosynostosis, it is noteworthy that the first affected generation in this family presented merely with isolated sagittal or unicoronal craniosynostosis and cutaneous syndactyly. Molecular analysis of MSX2 should therefore be considered in patients with isolated scaphocephaly/unicoronal synostosis, especially in the presence of a family history for craniosynostosis or syndactyly. © 2013 Wiley Periodicals, Inc.