Case Report Sagittal Craniosynostosis with Uncommon Anatomical Pathologies in a 56-Year-Old Male Cadaver
Total Page：16
File Type：pdf, Size：1020Kb
Hindawi Case Reports in Pathology Volume 2019, Article ID 8034021, 8 pages https://doi.org/10.1155/2019/8034021 Case Report Sagittal Craniosynostosis with Uncommon Anatomical Pathologies in a 56-Year-Old Male Cadaver Andrey Frolov ,1 Craig Lawson,1 Joshua Olatunde,1 James T. Goodrich,2 and John R. Martin III 1 1Center for Anatomical Science and Education, Department of Surgery, Saint Louis University School of Medicine, Saint Louis, MO 63104, USA 2Departments of Neurological Surgery, Pediatrics, Plastic and Reconstructive Surgery, Albert Einstein College of Medicine, Monteore Medical Center, Bronx, NY 10467, USA Correspondence should be addressed to John R. Martin III; [email protected] Received 1 May 2019; Revised 9 August 2019; Accepted 4 October 2019; Published 8 December 2019 Academic Editor: Evelina Miele Copyright © 2019 Andrey Frolov et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 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. ere 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. e craniotomy was unsuccessful (cephalic index, CI = 56) and resulted in abnormal vertical outgrowth of the craniotomized bone strip. e 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 identied as pathologic. Nine of those variants could be directly linked to CS with ve of them targeting RhoA GTPase signaling, with a potential to make it sustained in nature. e latter could trigger upregulated calvarial osteogenesis leading to premature suture fusion, skull bone thickening, and craniotomized bone strip outgrowth observed in the present case. 1. Introduction years, there is still much to be learned regarding the etiology of CS, particularly its genetic underlining [3]. CS is a condition that aects ~1 in 2,000–2,500 newborns and erefore, the main objectives of this study were to: (i) char- manifests itself as a premature fusion of a single or multiple acterize the craniofacial pathology (scaphocephaly) observed in cranial suture(s) leading to the deformation of a skull shape the 56-year-old cadaver and (ii) gain insights into its genetic [1–3]. e latter occurs due to a restriction of the skull growth component by identifying the respective genetic variants through in the direction perpendicular to the fused suture. Based on exome sequencing of DNA extracted from tissue procured from the etiology, CS can be classied as either primary or second- the donor’s body. A clearer understanding of the nature of the ary. e former occurs as a result of genetic, environmental, above pathology may help to better delineate the mechanism(s) or a combination of thereof factors specically targeting cra- responsible for its development, as a well as may improve out- nial sutures without causing a major pathological impact on comes of the specialized corrective clinical procedures. the rest of the human body. Secondary CS develops as a result of mechanical impacts, metabolic disorders such as hyperthy- roidism, hypercalcemia, vitamin D deciency etc. that targets 2. Case Presentation cranial sutures nonspecically, or due to premature suture closure as a result of the impaired developmental program that 2.1. Anatomical Characterization regulates brain growth [4]. In turn, primary CS can occur as an isolated event resulting in nonsyndromic CS, or it may less 2.1.1. Human Cadaveric Body Procurement. A 56-year-old frequently be associated with other anomalies leading to syn- male cadaver was received through Saint Louis University dromic CS [1–3]. Despite a signicant progress made in recent (SLU) School of Medicine Gi§ of Body Program from an 2 Case Reports in Pathology individual who had given his written informed consent. e by bisection of the bone and tongue. is procedure revealed available medical record indicated that this individual had a an exostotic hard palate (torus palatinus) and complete history of moderate mental retardation, cerebral palsy, seizure edentulism (Figure 2(c)). disorder, scoliosis, hydrocephalus, joint pain, mood disorder, anxiety disorder, encephalopathy and leukopenia. e cause 2.2. Histological Analysis. Sections of bony tissue from the of death was indicated as cerebral palsy. e cadaveric head sagittal strip revealed areas of immature compact bone was separated from the extremely contracted body and with incomplete or developing Haversian systems, whose embalmed using 2 : 1 mixture of ethylene glycol and isopropyl orientation was predominately perpendicular to the section alcohol. orientation (Figure 3(a)). Areas of immature bone were located on either side of randomly oriented bony spicules with marrow 2.1.2. CT Imaging. e initial visual examination of the spaces among them. ese marrow areas contained small foci embalmed patient’s head revealed its abnormal, scaphocephalic, of both red and white cell precursors, with larger numbers of shape as well as a presence of bulging sagittal bone strip unilocular adipocytes. (Figure 1(a)). e subsequent CT image analysis confirmed the More importantly, sections of bony tissue from surgically scaphocephaly (CI = 56) and demonstrated clearly a significant created margins revealed an extremely high number of oste- bone thickening in the scaphocephalic skull as compared to ons, with some, well-formed and others, formed incompletely mesocephalic skulls (Figure 1(b)). e respective fold change (Figures 3(b)–3(d)). In some areas, there was a lack of clear varied from 1.34 for occipital bone to 2.76 for parietal bone cement lines and there were also no osteoclasts or Howship with the rest of the scaphocephalic skull bone thickening falling lacunae present, nor were there any evidence of diploe. e into the ~1.6–2.3 fold range (Figure 1(c)). It should be noted, lack of cement lines, osteoclasts and diploe, along with the that the bone thickness values derived in the current report high number of osteons would be consistent with a massive from five mesocephalic skulls (Figure 1(c)) could be viewed as atypical bone overproduction without adequate compensatory a representative snapshot of a large respective sampling because bone degradation thereby leading to much thicker skull bone they were very similar to those reported for the group of 66 formation. male mesocephalic skulls [5]. 2.3. Genetic Analysis. e genetic underlining of the present 2.1.3. Craniectomy. Upon closer examination of the case was addressed by performing a genetic screen for the individual’s head it was concluded that he underwent, most putative variants using NGS technology applied to DNA likely early in infancy, a neurosurgical procedure, a sagittal extracted from the respective cadaveric tissue specimen as strip craniotomy, with a likely effort to correct the anomalous described previously [6, 7]. Additional experimental details skull shape and to reduce intracranial pressure. One of the pertinent to the performed bioinformatics analysis are most interesting features of the present case is an abnormal re- provided in the Supplementary Materials. growth of the surgically removed bone strip and the resultant e sequencing of the DNA coding regions (exome) elevated vertical displacement of the skull (Figure 2(a)). yielded 81 rare genetic variants (minor allele frequency, MAF It appears that the oval segment in question was resected ≤0.01) with predicted deleterious (pathological) implications and then replaced in situ without fixation or stabilization, (Table S1). Nine of those variants could be linked to the CS thereby permitting some adjustment of the calvarial vault development (Table 1) with the majority (five) targeting RhoA and potentially lowering the intracranial pressure from the GTPase activation either directly through ARHGAP21 and underlying cerebral hemispheres. Examination of the calvarial GMIP or indirectly through noncanonical Wnt signaling region revealed an oval segment of calvarial bone that included (INADL & RNF213) and/or PIEZO1 pathways (Table 1). e remnants of frontal and parietal bone with all suture lines remaining variants are those involved in the regulation of oste- obliterated (Figure 2(b)). is material was separated from the ogenesis/teeth development (BMP6) and cilia function surrounding calvarium by a variable band of grossly fibrous (CEP162, CROCC & DNAH11) (Table 1). It should be noted tissue that was adherent to edges of the original cranial bones that all nine variants are novel as they have never been reported and which was also adherent to the underlying dura. At a few in association with CS. locations there was a confluence of healed bone between the original, surgically created margins and the oval bone segment removed and replaced at the time of craniotomy (Figure 2(b)). 3. Discussion Also importantly, examination of the dural surface of the calvarium revealed several deep granular foveolae indicative e present case of craniofacial malformation could be of large arachnoid granulations in the sagittal strip (Figure 2(b)) described as a single suture sagittal CS with the additional that are likely to be the result of increased intracranial associated anatomical pathologies being torus palatinus and pressure. complete edentulism. is conclusion was made based on the measured CI of 56 (75–90 being normal) derived from the 2.1.4. Mandibulotomy. Physical examination of the respective CT images and the mandibulotomy results maxillofacial features of the cadaveric head revealed a large (Figures 1 and 2). It should be noted, that because without a underbite that prompted the dissection of the mandible to detailed medical history it is impossible to say when and how probe for additional abnormalities.