Sagittal Craniosynostosis and Related Cranial Anomalies: Genetic Insights

Abstract

BackgroundSagittal craniosynostosis (scaphocephaly) is a pathologic condition that results in premature fusion of the sagittal suture restricting the transverse growth of the skull leading to elevated intracranial pressure and consequent neurodevelopmental delay. It can occur most commonly as an isolated event resulting in nonsyndromic craniosynostosis, or it can occur less commonly in conjunction with other anomalies resulting in syndromic craniosynostosis. Although in past years close attention was paid by researchers regarding the mechanisms that govern development of craniosynostosis, much more remains to be learned about this cranial anomaly, in particular, the genetic mechanisms associated with scaphocephaly. The clearer understanding of the latter not only could shed more light on the respective mechanisms but could also help to improve and predict better outcomes of the respective corrective clinical procedures.ResultsThe present study reports a unique case of a male cadaver 56 years of age with sagittal craniosynostosis with a 0.56 cranial vault index as measured from respective radiographic images. Upon closer examination of the individual's head it was concluded that he underwent, most likely early in his life, a sagittal strip synostectomy with replacement. The additional maxillofacial anomalies included edentulous, mandibular prognathism with class 3 malocclusion and 15 mm of negative overjet, and exostosis of the hard palate. The latter was preliminary characterized as torus palatinus. One of the most interesting features of the present case was the abnormal appearance of the replacement bone strip and its vertical displacement that were accompanied by a presence of abnormal dura and venous sinuses with no brain indentations on the dural surface of the strip. Histologic analyses of cranial soft and hard tissues should help to clarify a nature of the respective pathologies. In order to better understand molecular mechanism(s) responsible for the development of sagittal craniosynostosis with the particular maxillofacial anomalies, the gene coding region (exome) of DNA extracted from the cadaveric tissue was screened for putative mutations employing Illumina Next Generation Sequencing Platform. This will help to unveil new genetic variations associated with the aberrant skull development in humans and optimize clinical approaches for its correction.ConclusionThe current case most likely represents syndromic sagittal craniosynostosis where surgical intervention was mainly unsuccessful resulting in abnormal development of the replacement bone strip and intracranial tissue.Support or Funding InformationThis study was supported by the Center for Anatomical Science and Education, Department of Surgery, Saint Louis University School of Medicine.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.