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Craniosynostosis and Related Disorders Mark S CLINICAL REPORT Guidance for the Clinician in Rendering Pediatric Care Identifying the Misshapen Head: Craniosynostosis and Related Disorders Mark S. Dias, MD, FAAP, FAANS,a Thomas Samson, MD, FAAP,b Elias B. Rizk, MD, FAAP, FAANS,a Lance S. Governale, MD, FAAP, FAANS,c Joan T. Richtsmeier, PhD,d SECTION ON NEUROLOGIC SURGERY, SECTION ON PLASTIC AND RECONSTRUCTIVE SURGERY Pediatric care providers, pediatricians, pediatric subspecialty physicians, and abstract other health care providers should be able to recognize children with abnormal head shapes that occur as a result of both synostotic and aSection of Pediatric Neurosurgery, Department of Neurosurgery and deformational processes. The purpose of this clinical report is to review the bDivision of Plastic Surgery, Department of Surgery, College of characteristic head shape changes, as well as secondary craniofacial Medicine and dDepartment of Anthropology, College of the Liberal Arts characteristics, that occur in the setting of the various primary and Huck Institutes of the Life Sciences, Pennsylvania State University, State College, Pennsylvania; and cLillian S. Wells Department of craniosynostoses and deformations. As an introduction, the physiology and Neurosurgery, College of Medicine, University of Florida, Gainesville, genetics of skull growth as well as the pathophysiology underlying Florida craniosynostosis are reviewed. This is followed by a description of each type of Clinical reports from the American Academy of Pediatrics benefit from primary craniosynostosis (metopic, unicoronal, bicoronal, sagittal, lambdoid, expertise and resources of liaisons and internal (AAP) and external reviewers. However, clinical reports from the American Academy of and frontosphenoidal) and their resultant head shape changes, with an Pediatrics may not reflect the views of the liaisons or the emphasis on differentiating conditions that require surgical correction from organizations or government agencies that they represent. those (bathrocephaly, deformational plagiocephaly/brachycephaly, and The guidance in this report does not indicate an exclusive course of treatment or serve as a standard of medical care. Variations, taking neonatal intensive care unit-associated skill deformation, known as into account individual circumstances, may be appropriate. NICUcephaly) that do not. The report ends with a brief discussion of All clinical reports from the American Academy of Pediatrics microcephaly as it relates to craniosynostosis as well as fontanelle closure. automatically expire 5 years after publication unless reaffirmed, revised, or retired at or before that time. The intent is to improve pediatric care providers’ recognition and timely This document is copyrighted and is property of the American referral for craniosynostosis and their differentiation of synostotic from Academy of Pediatrics and its Board of Directors. All authors have filed deformational and other nonoperative head shape changes. conflict of interest statements with the American Academy of Pediatrics. Any conflicts have been resolved through a process approved by the Board of Directors. The American Academy of Pediatrics has neither solicited nor accepted any commercial involvement in the development of the content of this publication. INTRODUCTION DOI: https://doi.org/10.1542/peds.2020-015511 Address correspondence to Mark S. Dias, MD, FAAP, FAANS. Pediatric health care providers evaluate and care for children with E-mail: [email protected] a variety of head shapes, some of which represent craniosynostosis and PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275). other craniofacial disorders, some of which are deformational in nature, and some of which are simply normal variants. Identifying the various Copyright © 2020 by the American Academy of Pediatrics types of head shape abnormalities is important for aesthetics, to identify candidates for future monitoring, and, at least in some, to prevent To cite: Dias MS, Rizk EB, et al. AAP SECTION ON NEUROLOGIC increases in intracranial pressure (ICP) and allow proper brain SURGERY,SECTIONONPLASTICANDRECONSTRUCTIVESURGERY. development. This report reviews several of the important head shape Identifying the Misshapen Head: Craniosynostosis and Related Disorders. Pediatrics. 2020;146(3):e2020015511 abnormalities and normal variants that pediatric health care providers are Downloaded from www.aappublications.org/news by guest on September 5, 2020 PEDIATRICS Volume 146, number 3, September 2020:e2020015511 FROM THE AMERICAN ACADEMY OF PEDIATRICS likely to see, describes their salient (bregma) forms at the junction of the Undifferentiated cells between these clinical and radiologic features, and paired frontal and parietal bones, osteogenic bone fronts form the discusses the optimal timing for whereas the posterior fontanelle (l) cranial vault sutures, which function referral and surgical correction. The forms at the junction of the paired to keep the suture patent while report begins with an overview of the parietal bones with the midline allowing rapid and continual bone normal development of the skull and occipital bone. formation at the edges of the bone sutures and the pathophysiology of front until brain growth is The skull encompasses the skull base, craniosynostosis. complete.10 Sutures are fibrous calvarial vault, and pharyngeal “joints” that allow temporary skeleton.1,2 The bones of the skull deformation of the skull during base mineralize through NORMAL DEVELOPMENT OF THE parturition or trauma, inhibit bone CALVARIUM AND MOLECULAR endochondral ossification involving separation for the protection of DETERMINANTS OF CRANIOSYNOSTOSIS the replacement of a fully formed underlying soft tissues, and, perhaps cartilaginous anlagen with bone The skull is a complex skeletal system most importantly, enable growth matrix. In contrast, the bones of the that meets the dual needs of along the edges of the 2 opposing calvarial vault form by protecting the brain and other bones until they ossify and fuse later intramembranous ossification sensory organs while allowing its in life.10,11 Sutures normally remain involving the mineralization of bone ongoing growth during development. unossified well into adolescence. matrix from osteoblasts without The calvarial vault (Fig 1) is When sutures mineralize (close) a cartilaginous intermediate. composed of paired frontal, parietal, abnormally, growth is prevented at Craniosynostosis involves the and temporal bones and a single the fused suture and is instead abnormal mineralization of suture(s) occipital bone. The paired frontal redirected to other patent sutures, and fusion of one or multiple bones are separated from each other which, in turn, alters the shape of the contiguous bones of the cranial vault by the midline metopic suture, and skull in predictable ways. and can include additional the paired parietal bones are abnormalities of both the soft and separated from each other by the Research has revealed multiple hard tissues of the head.3 The role of midline sagittal suture. The frontal genetic factors, involving several cartilage growth disturbance within and parietal bones are separated by major cellular signaling pathways the cranial base in craniosynostosis is the paired coronal sutures, the – such as wingless and Int-1 (WNT), still a matter of debate.4 7 parietal and temporal bones are bone morphogenetic protein (BMP), separated by the paired squamosal The bones of the cranial vault ossify fibroblast growth factor (FGR), and sutures, and the parietal and occipital directly from undifferentiated others, that interact to direct the bones are separated by the paired mesenchyme.8,9 Differentiating behavior of particular subpopulations lambdoid sutures. There are also osteoblasts accumulate on the leading of cells within the suture. In a number of sutures and edges of cranial vault bones as the craniosynostosis, these cells receive synchondroses involving the skull brain expands during prenatal and and emit signals that stimulate base. The anterior fontanelle early postnatal growth. osteogenic differentiation far earlier than expected,12 resulting in mineralization and progressive ossification that unites the bones on either side of the suture. Pathogenic variants of fibroblast growth factor receptors (FGFRs) are the most common genetic variants associated with craniosynostosis.13–15 FGFRs are transcription factors that initiate and regulate the transcription of multiple genes throughout prenatal development.16–21 Various mouse models expressing FGFR pathogenic variants have been developed and FIGURE 1 demonstrate phenotypes analogous Three-dimensional CT scan showing (A) top and (B) side views of the skull bones with metopic (m), sagittal (s), coronal (c), lambdoid (l), and squamosal (sq) sutures, as well as the anterior fontanelle to the human craniosynostosis (af). Reproduced with permission from Governale LS. Craniosynostosis. Pediatr Neurol. 2015;53(5): syndromes, including premature 394-401. coronal suture closure and midface Downloaded from www.aappublications.org/news by guest on September 5, 2020 2 FROM THE AMERICAN ACADEMY OF PEDIATRICS – flattening (retrusion).22 31 Pathogenic To what extent, if any, treatable 2. Bone is, therefore, deposited variants in TWIST1 (twist family basic causes contribute to neurocognitive asymmetrically, with greater Helix-Loop-Helix transcription factor deficits in craniosynostosis, and osseous deposition in the bones 1) gene, another transcription factor whether prompt surgical
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