Sagittal Craniosynostosis with Uncommon Anatomical Pathologies in a 56-Year-Old Male Cadaver

Abstract

Sagittal craniosynostosis (CS) is a pathologic condition that results in premature fusion of the sagittal suture, restricting the transverse growth of the skull leading in some cases to elevated intracranial pressure and neurodevelopmental delay. There is still much to be learned about the etiology of CS. Here, we report a case of 56-year-old male cadaver that we describe as sagittal CS with torus palatinus being an additional anomaly. The craniotomy was unsuccessful (cephalic index, CI = 56) and resulted in abnormal vertical outgrowth of the craniotomized bone strip. The histological analysis of the latter revealed atypical, noncompensatory massive bone overproduction. Exome sequencing of DNA extracted from the cadaveric tissue specimen performed on the Next Generation Sequencing (NGS) platform yielded 81 genetic variants identified as pathologic. Nine of those variants could be directly linked to CS with five of them targeting RhoA GTPase signaling, with a potential to make it sustained in nature. The latter could trigger upregulated calvarial osteogenesis leading to premature suture fusion, skull bone thickening, and craniotomized bone strip outgrowth observed in the present case.

Two Cases of Sporadic Amyotrophic Lateral Sclerosis With Contrasting Clinical Phenotypes: Genetic Insights

“…The whole exome sequencing (WES) on the Next-Generation Sequencing (NGS) platform and bioinformatics analysis were performed as previously described [ 6 , 7 ], with the following modifications. DNA extracted from the tibia specimens procured from the embalmed subject bodies was sequenced to a 30× depth of coverage (~4.5 Gb) on the Illumina HiSeq 2500 NGS platform in the 2 × 100 base read format.…”

“…The variant call and annotation were performed by the Genome Technology Access Center (GTAC, Washington University in St. Louis) using SnpSift varType and DRAGEN. The resultant data were presented in Microsoft Excel format, and rare (minor allele frequency (MAF) ≤ 0.01) pathologic/deleterious variants were identified through five consecutive filtering steps described elsewhere [ 6 , 7 ]. The three final filtering steps in the bioinformatics analysis employed the SIFT [ 8 ], PolyPhen_2-HDIV [ 9 ], and PROVEAN [ 10 ] algorithms.…”

“…The WES on the Illumina NGS platform revealed that DNA procured from D1 and D2 had a set of five shared genes affected in both donors by rare mutations (MAF ≤ 0.01) that were identified through a very stringent bioinformatics analysis [ 6 , 7 ] as pathologic/deleterious (Table 1 ). Importantly, genetic variants in three of those genes, BBS12 , HLA-DQB1 , and MUC20 , were exact matches between D1 and D2 (Group I) (Table 1 ).…”