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 October 1, 2021 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 October 1, 2021 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 treatment opposite the perimeter sutures of – associated with craniosynostosis,32 34 can improve neurobehavioral the combined growth plate; directly affect BMP signaling of skull outcomes, is a matter of debate. 3. Non-perimeter sutures that are in- preosteoblasts, leading to variations Elevated ICP is present in 4% to 42% line with the combined bone plate 35 in cerebral brain angiogenesis. of children with single-suture deposit bone symmetrically at These animal models as well as craniosynostosis and approximately their suture edges; and studies of cellular behavior in human 50% to 68% with multisutural – 4. Both perimeter and in-line craniosynostosis cell lines provide the involvement40 44; the incidence of (abutting) sutures nearest the means to examine the structural, intracranial hypertension is higher combined bone plate compensate cellular, and molecular changes that among older untreated with greater osseous deposition occur during prenatal individuals.42,44 Elevated ICP than more distant sutures. development.36,37 correlates with developmental and 40 cognitive outcomes in some studies To use sagittal synostosis as an 39,45,46 but not others. Neither has the example, the fused parietal bones act severity of the deformity correlated THE EFFECT OF CRANIOSYNOSTOSIS ON as a single, combined growth plate with the presence of neurocognitive with reduced growth perpendicular ICP AND DEVELOPMENT 39 deficits. A few studies have to the sagittal suture; accelerated Aesthetic consequences aside, there suggested that earlier treatment of bone deposition occurs within the are concerns that craniosynostosis, in craniosynostosis may result in better frontal and occipital bones. The some cases, affects brain growth and early and late neurocognitive metopic suture, as an abutting in-line 45,47 intellectual development. A recent outcomes, but the majority have suture, deposits bone symmetrically 12,48–50 systematic review strongly suggests not found such an association. at an accelerated rate. The result is an that craniosynostosis is associated Finally, genes involved in elongated head (scaphocephaly) with with a higher risk for presurgical craniosynostosis syndromes have parietal narrowing as well as frontal neurocognitive deficits compared recently been found to be involved in and occipital bossing. A similar 51 with the population unaffected by brain development, and syndromic analysis predicts the head shape for craniosynostosis; these deficits craniosynostosis syndromes having the other sutural synostoses (Fig 2). persist postoperatively, suggesting virtually identical patterns of skull Multisutural synostosis can be that they may occur independent of fusion may carry widely different appreciated as the combined effect of 38 surgical correction. Generalized IQ risks for neurodevelopmental deficits fusion involving each of the individual is shifted downward with increased (see below). component sutures. learning disabilities, language delays, and behavioral difficulties.39 At least THE IMPACT OF SUTURAL SYNOSTOSIS SCAPHOCEPHALY (SAGITTAL 4 mechanisms have been proposed: ON DIRECTED CALVARIAL GROWTH SYNOSTOSIS), DOLICHOCEPHALY (1) globally elevated ICP, (2) global (NICUCEPHALY), AND BATHROCEPHALY brain hypoperfusion, (3) localized Single sutural synostosis results in predictable changes in skull shape compression and deformity, and (4) 52 Sagittal synostosis is the most genetic predisposition. It has proven (Fig 2, Table 1). Persing et al common form of craniosynostosis, difficult to extract the exact proposed 4 rules that govern calvarial accounting for approximately 40% to contributions of each factor, and growth and predict the head shape in 45% of cases53–55 and having studies have provided conflicting cases of craniosynostosis. These rules a prevalence of 2 to 3.2 per 10 000 data. Moreover, many studies suffer are based on the principle that live births.53,56,57 Sagittal synostosis from a variety of methodologic flaws, calvarial growth occurs by osseous has a distinct male predominance of including the inclusion of several deposition from calvarial bones lying 2.5 to 3.8:1.53,55 Sagittal synostosis types of craniosynostosis, varying adjacent to each suture, and this produces scaphocephaly, definitions of ICP elevations (and lack deposition is oriented perpendicular characterized by both an elongated of normative data), the use of to the intervening suture: head and biparietal narrowing that is different neurocognitive testing 1. Bones that are fused as a result of evident at birth. The head elongation strategies, lack of randomization, craniosynostosis act as is best appreciated by looking at the inconsistent operative approaches, a “combined growth plate,” having infant from the side (Fig 3). Some variations in operative timing, and reduced growth potential at all of patients have an associated saddle small study cohorts, to name a few. the margins of the plate; deformity at the vertex, giving an

Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 146, number 3, September 2020 3 FIGURE 2 Drawing showing the various head shape changes that occur with single-suture synostosis and deformational posterior plagiocephaly. Reproduced with permission from the cover of the May 2016 issue of the Journal of Neurosurgery: Pediatrics. ©2016 American Association of Neurologic Surgeons. Artist: Stacey Krumholtz. overall “peanut” shape to the head. Normally, the parietal bones project produces a “cone-head” or bullet- The second consistent abnormality is straight up or even bowed outward shaped head when viewed from the the biparietal narrowing when looked from the temporal region. Biparietal front and a bicycle racing helmet at from the front or from above. narrowing in sagittal synostosis shape when viewed from above

Downloaded from www.aappublications.org/news by guest on October 1, 2021 4 FROM THE AMERICAN ACADEMY OF PEDIATRICS TABLE 1 Head Shapes Resulting From Craniosynostosis and Positional Deformations Type Head Shape Name 1° Change 2° Change(s) Sagittal Scaphocephaly Elongated AP distance Biparietal narrowing, frontal and/or occipital bossing, and occasional saddle deformity NICUcephaly Dolichocephaly Elongated AP distance Lack of biparietal narrowing and frontal/occipital bossing Metopic Trigonocephaly Triangular forehead Bilateral orbital retrusion, bitemporal narrowing, and hypotelorism Unicoronal Plagiocephaly Trapezoid Flattened ipsilateral forehead, retruded and elevated ipsilateral orbit (Harlequin eye), ipsilateral nasal root and contralateral nasal tip deviation, and anterior displacement of ipsilateral ear Bicoronal Brachycephaly and Shortened AP distance; flat, Exorbitism if associated midface hypoplasia is present turricephaly tall, and wide forehead Unilambdoid Plagiocephaly Trapezoid Bulge behind ipsilateral ear or mastoid and ear displaced posterior and inferior Bilambdoid Brachycephaly Shortened AP distance, flat Bulge behind both ears or mastoid and both ears displaced posterior and inferior occiput Frontosphenoidal Plagiocephaly Trapezoid Retruded and depressed ipsilateral orbit and contralateral nasal root and ipsilateral nasal tip deviation DP Plagiocephaly Parallelogram Ipsilateral occiput, ear, and forehead all displaced anteriorly DB Brachycephaly Shortened AP distance Flattened occiput with normal forehead and orbits

(Fig 3). Frontal or occipital bossing is and a bullet-shaped head on anterior- radiation exposure, particularly with a variable feature and tends to posterior (AP) radiographs (Fig 4A thin slices. worsen as the infant ages. Physical and B). The normal sagittal suture It is important to distinguish examination also demonstrates tapers toward the midline on AP scaphocephaly from dolichocephaly. a prominent midline interparietal, or radiographs; in sagittal synostosis, Although these 2 terms have been sagittal, ridge that extends between the fused sagittal suture may not be used interchangeably by many, the anterior and posterior visible, but, more commonly, it dolichocephaly refers to an elongated fontanelles; the sagittal suture is appears to have an abrupt, more head without associated biparietal longer, as measured from the anterior squared-off appearance (Fig 4B), narrowing and is caused by to the posterior fontanelles. Partial paradoxically appearing to be open positioning. Dolichocephaly most when, in fact, it is not. Computed synostosis may cause an incomplete commonly occurs in preterm infants tomography (CT) scans demonstrate ridge involving only a portion of the in the NICU: so-called NICUcephaly. Of the elongated head with biparietal suture. One may demonstrate the course, there is no midline sagittal narrowing (Fig 4C); the fused sagittal fusion of the 2 parietal bones by ridge as there is in sagittal synostosis, suture is best appreciated on coronal placing a thumb on each of them near and, with the thumb maneuver reconstructions by using bone the midline and alternatingly described above, the parietal bones algorithms (Fig 4D); three- depressing each of them; there should will move independently, often dimensional reconstructions are be no independent movement. making the infant cry because this particularly well suited to appears to be painful. Sagittal synostosis produces an demonstrate the midline sagittal elongated head on lateral radiographs ridge (Fig 4E) but may involve more Infants with frontal bossing from hydrocephalus or chronic subdural hematomas or hygromas may generate confusion. However, these infants have neither an elongated head nor biparietal narrowing, and they have no midline sagittal ridge. Metopic synostosis is readily differentiated from sagittal synostosis by the presence of a prominent midline ridge that extends from the nasion to the anterior fontanelle, anterior to the sagittal suture, and is FIGURE 3 often associated with a triangular or Scaphocephaly attributable to sagittal synostosis. A, Lateral view shows elongated antero-posterior dimension with modest frontal bossing and saddle deformity at vertex. B, Frontal view in same child keel-shaped forehead shows parietal bones that curve inward giving a conical head shape attributable to parietal (trigonocephaly) with recession of the narrowing. lateral orbits and narrow set eyes.

Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 146, number 3, September 2020 5 FIGURE 4 Radiologic features of sagittal synostosis. A, Lateral skull radiograph demonstrates an elongated head (sagittal suture is difficult to see from this perspective). B, Anteroposterior skull radiograph shows conical head shape. Note that part of the sagittal suture appears fused (arrowhead), whereas some appears open with sharp borders and adjacent hyperdensities (arrows). The entire suture was fused at surgery. C, Axial CT scan shows elongated head shape with prominent frontal bossing and fused posterior sagittal suture (arrowhead). D, Coronal CT scan shows conical shape of head with fusion of the sagittal suture (arrowheads). E, Three-dimensional CT scan shows prominent midline ridged sagittal suture (arrowheads); both coronal and lambdoid sutures are patent.

Bathrocephaly is another condition forms of synostosis. Surgical craniosynostosis, accounting for 19% – that can produce confusion. management options include both to 28% of cases53 55 and having Bathrocephaly results in a prominent open and endoscopic repairs; a prevalence of 0.9 to 2.3 per 10 000 occiput that angles sharply inward adjunctive postoperative helmet live births.53,57 The prevalence of toward the neck but without frontal therapy is recommended for up to metopic synostosis may have bossing, biparietal narrowing, or 1 year postoperatively, after more increased over the past decades sagittal ridging (Fig 5). Bathrocephaly limited endoscopic repairs.59,60 The (without a corresponding increase in is associated with a persistent importance of early recognition and other synostoses) for uncertain mendosal suture, an embryonic referral for surgical management reasons.54 Metopic synostosis also suture that extends transversely cannot be overemphasized because has a distinct male preponderance of between the 2 lambdoid sutures and, infants treated after 6 to 10 months 1.8 to 2.8:1.53,55 Metopic synostosis normally, is gone by birth Fig 5C.58 of age increasingly require more produces trigonocephaly with Bathrocephaly does not require extensive and morbid complete reduced growth potential treatment. calvarial vault remodeling to achieve perpendicular to the metopic suture, adequate correction. a pronounced metopic ridge, and Infants who have sagittal synostosis hypotelorism; the forehead forms should be referred to a specialist for a keel, similar to the prow of a boat, TRIGONOCEPHALY (METOPIC repair as early as possible because with bilateral orbital retrusion and SYNOSTOSIS) surgical correction is usually bitemporal narrowing (Fig 5). performed much earlier (often at Metopic synostosis is presently the Reduced bifrontal and accelerated 6–12 weeks of age) than for other second most common form of biparietal growth along the coronal

Downloaded from www.aappublications.org/news by guest on October 1, 2021 6 FROM THE AMERICAN ACADEMY OF PEDIATRICS FIGURE 5 Bathrocephaly attributable to persistent mendosal suture. A, Infant with focal prominent occiput (arrowheads). Note the lack of frontal bossing. B, Lateral skull radiograph shows prominent occiput (black arrowhead) and steep angle of the posterior skull (white arrowhead). C, CT scan shows persistent mendosal suture (arrowheads). sutures, with additional symmetrical Plain radiographs may display craniosynostosis, accounting for 12% growth along the in-line sagittal prominent bony fusion of the metopic to 24%53,55 of nonsyndromic cases suture, results in a widened, pear- suture; however, care must be taken and with a prevalence of 0.7 per shaped calvarium behind the coronal because the metopic suture may 10 000 live births.57 Unlike other suture (Fig 6B). normally begin closing as early as forms of synostosis that have a male 3 months of age and all are closed by predominance, unicoronal synostosis 61 Some infants may display only 9 months of age. CT scans readily has a female preponderance of 1.6 to a palpable (and sometimes visible) demonstrate the triangular-shaped 3.6:1.53,57 Unicoronal synostosis metopic ridge with little or no anterior fossa with midline thickening produces anterior plagiocephaly in trigonocephaly; whether this of the metopic suture and which growth along the ipsilateral represents a forme fruste of hypotelorism (Fig 7). coronal suture is reduced and results metopic synostosis or another in a flattening of the ipsilateral distinct process is unknown. ANTERIOR PLAGIOCEPHALY forehead (Fig 8). Accelerated growth Infants with an isolated metopic (UNICORONAL SYNOSTOSIS) of the contralateral frontal bone along ridge and minimal or no the perimeter (metopic) and in-line trigonocephaly do not require Unicoronal synostosis is the third surgical correction. most common form of (contralateral frontal) sutures results in compensatory bossing of the contralateral forehead. Some parents and providers may focus on the contralateral compensatory bossing rather than the ipsilateral flattening on the involved side. The metopic suture is bowed toward the side of the flattening. Accelerated growth along the squamosal suture (another perimeter suture) also produces a degree of ipsilateral temporal bossing as well as posterior and inferior ear displacement. The net effect of these changes is a trapezoidal head shape with flattening of the ipsilateral calvarium (both frontally and occipitally) compared to the contralateral side FIGURE 6 (Fig 8A). This presentation stands in Trigonocephaly attributable to metopic synostosis. A, Frontal view of infant showing pronounced midline metopic ridge and bilateral temporal narrowing. B, Vertex view in the same infant shows distinct contrast to the parallelogram triangular-shaped forehead. head shape that accompanies most

Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 146, number 3, September 2020 7 ipsilateral anterior skull base deviates the nasal root toward the involved side and the nasal tip toward the contralateral side (Fig 8B), and the ipsilateral tragus is often displaced anteriorly and inferiorly. In some cases, the entire face appears to be curved with its convexity toward the involved side, leading to a “facial scoliosis” (Fig 8B).

Plain radiographs demonstrate poor visualization of the involved coronal suture. If visible, the ipsilateral suture is deviated anteriorly compared to FIGURE 7 the contralateral suture; one caveat is Radiologic features of trigonocephaly. A, Axial CT shows triangular-shaped forehead with fused that the radiograph must be truly metopic suture (arrowhead) and bitemporal narrowing. B, Three-dimensional CT scan vertex lateral by demonstrating that the ears reconstructions show prominent midline metopic ridge with triangular-shaped forehead, bilateral and/or external ear canals are orbital retrusion, and hypotelorism. properly aligned. On the AP view, a characteristic “Harlequin” (or “ ” cases of occipital deformational with foreshortening of the zygoma Mephistophelean ) orbit is visible on plagiocephaly (DP) (see below). and orbit results in a characteristic the involved side and is attributable elevation of the ipsilateral eyebrow, to elevation of the lesser sphenoid Coronal synostosis additionally a seemingly larger palpebral fissure, wing (Fig 9A). The nasal bone is also involves the sphenozygomatic, and/or mild proptosis (Fig 8). The askew, with its upper part deviated frontosphenoidal, and contralateral orbit may be toward the involved side. sphenoethmoidal sutures along the comparatively smaller and is The findings of unicoronal synostosis frontal skull base, which produces displaced inferiorly and laterally, are also readily apparent on CT scans. additional secondary morphologic sometimes leading to a vertical The involved coronal suture is not changes involving the orbits and face. orbital malalignment (dystopia). visible over most or all of its length, Elevation of the lateral sphenoid wing Diminished growth along the whereas the contralateral side is readily apparent on axial images. The ipsilateral flattening and contralateral bossing are also readily evident on axial images. Finally, the sphenoid wing elevation produces a distinct asymmetry to the skull base, with the ipsilateral orbital roof being visible on more superior axial images (and elevated on coronal images) compared to the contralateral orbital roof (Fig 9B). Coronal images also demonstrate the Harlequin orbit to good advantage. Three-dimensional CT reconstructions also demonstrate all of the findings.

The differential diagnosis would FIGURE 8 include occipital DP and Anterior plagiocephaly attributable to unilateral coronal synostosis. A, Vertex view in a child with left frontosphenoidal synostosis, both coronal synostosis shows flattening of the left forehead and compensatory prominence of the right discussed below. Hemifacial forehead, upward displacement of the left eyebrow, deviation of the nasal root toward the right and microsomia is another consideration, nasal tip toward the left, and trapezoidal head shape. B, Frontal view in another infant with right coronal synostosis shows elevation of the right eyebrow and misshapen orbit, deviation of the nasal although the latter is manifest by root toward the right and nasal tip toward the left, and significant facial scoliosis. primary underdevelopment of the

Downloaded from www.aappublications.org/news by guest on October 1, 2021 8 FROM THE AMERICAN ACADEMY OF PEDIATRICS POSTERIOR SYNOSTOTIC PLAGIOCEPHALY (LAMBDOID SYNOSTOSIS) Lambdoid synostosis is rare; in contemporary series, lambdoid synostosis accounts for only 2% of cases and has a prevalence of 0.1 per 10 000 live births.55,57 Older studies likely included children with DP and their prevalence rates are, therefore, higher. In one small series, male and female patients were equally represented.55 True lambdoid synostosis is usually readily FIGURE 9 differentiated from occipital DP (see Radiologic features of unilateral coronal synostosis. A, A-P radiograph shows elevated ipsilateral below), with which it is most sphenoid wing giving rise to the Harlequin eye deformity (arrowheads). The nasal bone is deviated commonly confused. True lambdoid superiorly toward the fused suture. B, Axial CT scan shows trapezoidal head shape with retrusion of the right forehead (white arrowhead), prominence of the left forehead (black arrowhead), and synostosis is most commonly elevation of the sphenoid wing (white arrow). characterized by a flattening of both the ipsilateral occiput and forehead, midface and mandible, with deformities are present with leading to a trapezoidal or relative sparing of the forehead elevation of both sphenoid wings. rhomboidal head shape (Fig 12). The and orbits; the ear is also malformed, Because both frontal bones are contralateral occiput may be and there are often preauricular involved, the nasal bone remains prominent by comparison. The skin tags. midline. CT scans demonstrate lambdoid suture is prominently brachycephaly, thickening and/or ridged. The ipsilateral ear is deviated ANTERIOR BRACHYCEPHALY nonvisualization of both coronal posteriorly (in contrast to DP, in (BICORONAL SYNOSTOSIS) sutures, a shallow anterior which it is deviated anteriorly), and fossa and orbits, and bilateral the mastoid process and associated Bicoronal synostosis accounts for sphenoid wing elevation (Fig 11). retromastoid occipital bone are about 3% of nonsyndromic and most Coronal images nicely demonstrate unusually prominent, producing syndromic synostoses,53 with bilateral Harlequin orbits as a retroauricular “bulge” (Fig 12). a prevalence of approximately 0.5 per well. Bilateral involvement produces 10 000 live births.57 In bicoronal synostosis, the coronal sutures are palpable on both sides, the entire forehead is flattened, the head is reduced in the anteroposterior dimension (anterior brachycephaly), and the forehead often has a towered appearance (turricephaly). The combination of frontal and maxillary foreshortening results in shallow orbits and produces significant exophthalmos; in addition, the orbits are recessed (retruded) or shallow bilaterally (Fig 10). The nasal bone is short and upturned in many cases. On radiographs, the anterior fossa and orbits are short and both FIGURE 10 coronal sutures are radio dense or Brachycephaly attributable to bicoronal synostosis in a child with Saethre-Chotzen syndrome. A,- Frontal view shows flattened forehead, shallow orbits with bilateral orbital retrusion, a modes- difficult to see and anteriorly tly upturned (beaked) nose, bilateral ptosis, and midface hypoplasia. B, Lateral view of the same deviated. Bilateral Harlequin orbit infant shows flattened and tall (turricephaly) forehead, with shallow orbits and midface hypoplasia.

Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 146, number 3, September 2020 9 FRONTOSPHENOIDAL SYNOSTOSIS An extremely rare form of synostosis involves the frontosphenoidal suture, located at the anterior skull base and contiguous with the coronal suture and orbital roof.62,63 Synostosis involving the frontosphenoidal suture produces plagiocephaly with ipsilateral forehead flattening that resembles unilateral coronal synostosis but differs from the latter in that the ipsilateral orbit is deviated inferiorly rather than superiorly, and the nasal root is deviated away from rather than toward the side of the FIGURE 11 synostosis (Fig 13 A and B). The Radiologic features of bilateral coronal synostosis. A, Axial CT scan shows shallow anterior fossa coronal suture is visible on and absence of both coronal sutures (arrowheads). B, Three-dimensional CT scan reconstructed vertex view shows shallow anterior fossa, bilateral superior orbital retrusion, and bilaterally fused neuroimaging studies, and there is no coronal sutures (arrowheads). Harlequin eye orbital deformity (Fig 13 C and D); CT demonstrates the fusion of the frontosphenoidal fl a attened occiput with ridging of lambdoid suture(s). The retromastoid suture (Fig 13E). Treatment involves both lambdoid sutures and bulge and posterior displacement of a fronto-orbital reconstruction.62,63 retromastoid bulge on both the petrous ridge are prominent; the sides. The posterior sagittal suture posterior midline and the foramen SYNDROMIC CRANIOFACIAL may also be involved, producing an magnum at the base of the skull are MALFORMATIONS element of scaphocephaly as well as also drawn toward the ipsilateral side ridging of both lambdoid and (Fig 12C). Three-dimensional CT A number of craniosynostosis posterior sagittal sutures (the scans also demonstrate these syndromes have been described “Mercedes-Benz” sign). findings to good advantage phenotypically (Table 2). All of these, (Fig 12D). Treatment involves most commonly, include elements of Plain radiographs commonly open posterior cranial vault bicoronal synostosis and midface demonstrate significant reconstruction between 5 and hypoplasia. Ophthalmologic prominence and hyperostosis or 9 months of age or endoscopic manifestations are also common and nonvisualization of the involved repair as early as 2 to include shallow orbits, some degree lambdoid suture(s). CT scans also 3 months of age, followed by of exorbitism, and extraocular muscle demonstrate hyperostosis or molding helmet treatment for up to dysfunction with strabismus and nonvisualization of the involved 1 year. resultant amblyopia and poor visual

FIGURE 12 Unilateral lambdoid synostosis. A, Anterior view shows asymmetric head with calvarium deviated toward the left. Note the symmetry of orbits. B, Posterior view shows prominent curvature of the occiput toward the left with a retromastoid bulge on the right (arrow) and flattening inferior to the bulge. C, Axial CT scan shows prominent left mastoid bulge and indentation of the occipital skull (arrowhead). D, Three-dimensional CT scan posterior view shows the fused left lambdoid suture, retromastoid bulge (white arrowheads), and indentation of the occipital bone (black arrowhead).

Downloaded from www.aappublications.org/news by guest on October 1, 2021 10 FROM THE AMERICAN ACADEMY OF PEDIATRICS FIGURE 13 Frontosphenoidal synostosis. A, Frontal view of infant with left frontosphenoidal synostosis, with left forehead depression and retrusion and depression of left orbit. B, Vertex view demonstrating left forehead and orbital retrusion. Note in both images the deviation of the nasal root away from, and the nasal tip toward, the involved side, in contrast to coronal synostosis. C, Frontal three-dimensional reconstruction CT scan shows inferiorly displaced ipsilateral eyebrow and orbital roof (arrowheads) and deviation of the nasal root (arrow) toward the contralateral side (in contrast to unicoronal synostosis, see Fig 8). D, Vertex three-dimensional reconstruction CT scan shows left forehead flattening but open coronal suture on that side (arrowheads). E, Three- dimensional reconstruction CT scan with a view of the inside of the skull base with the calvarium digitally subtracted shows flattening of the left orbit. The right frontosphenoidal suture is patent (arrowhead), whereas the left is fused. acuity.64,65 More recent genetic resulting from different genetic interested reader is referred testing has revealed significant pathogenic variants. It is beyond the elsewhere for more detailed genotypic overlap, with the same scope of this report to describe all of information.66,67 genetic mutation capable of the various syndromes in detail; brief Crouzon Syndrome producing distinctly different descriptions of the more common phenotypes, and a single phenotype syndromes are provided. The Crouzon syndrome is most frequently characterized by bicoronal synostosis leading to a shallow anterior fossa, TABLE 2 Genetics of Craniofacial Syndromes a high and flat forehead fi Syndrome Transmission Identi ed Gene Variants (turricephaly) with reduced Crouzon AD FGFR1, FGR2 anteroposterior cranial measurement Apert AD FGFR2 (brachycephaly), shallow orbits and Pfeiffer AD FGFR1, FGR2 Saethre-Chotzen AD TWIST prominent globes (exorbitism), Carpenter AR RAB23, MEGF8 midface hypoplasia leading to an Antley-Bixler AR and sporadic AD transmission Uncertain (for AR) and FGFR2 (for AD) underbite and malocclusion, and Muenke AD FGFR3 upturned (or “beaked”) nose. AD, autosomal-dominant; AR, autosomal-recessive. Involvement of other sutures may

Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 146, number 3, September 2020 11 also occur, and progressive sutural and III are associated with much fusion has been described during the more severe involvement, usually first 2 years of life.68 Craniosynostosis involving all of the sutures (and, in is a variable feature and, rarely, may type II, producing a cloverleaf skull), be absent. Syndactyly is notably with shallow orbits and severe absent. Rarely, vertebral fusion, exorbitism sufficient to produce ankylosis (particularly the elbows), corneal exposure, airway obstruction, and acanthosis nigricans may be partial syndactyly and elbow present. Cognitive development is ankylosis, various visceral often normal, and neurocognitive abnormalities, and moderate to deficits are uncommon. Crouzon severe neurocognitive impairment. syndrome is transmitted as an Saethre-Chotzen Syndrome autosomal-dominant condition with varying penetrance; pathogenic Saethre-Chotzen syndrome is variants in the FGFR1 or FGFR2 genes characterized by bicoronal synostosis are responsible for all but Crouzon (with occasional involvement of other with acanthosis nigricans, which is sutures) leading to turricephaly and caused by pathogenic variants in the brachycephaly with biparietal FGFR3 gene. foramina but less severe midface FIGURE 14 hypoplasia and modest exorbitism. Apert Syndrome Syndactyly involving the toes in an infant with Differentiating manifestations include Apert syndrome. The craniosynostosis pattern in Apert ptosis of the eyelids (Fig 10A), a low syndrome is similar to that in anterior hairline, and a prominent Crouzon syndrome, although also be present. Apert syndrome is nose. Lacrimal duct abnormalities progressive fusion of additional transmitted as an autosomal- and a characteristic prominent ear sutures during the first 2 years occurs dominant condition; a mutation in the crus may be present. Extracranial more commonly in Apert syndrome. FGFR2 gene is responsible. abnormalities can include partial soft Like in Crouzon syndrome, tissue syndactyly, most commonly turricephaly, brachycephaly, Pfeiffer Syndrome involving the second and third fingers exorbitism, beaked nose, and and third and fourth toes; the digits Pfeiffer syndrome is characterized by malocclusion are cardinal clinical are often short and the great toes may bicoronal synostosis, and the midface manifestations in Apert syndrome. be broad. Saethre-Chotzen syndrome is narrow but not generally retruded; Down-slanting palpebral fissures are is transmitted as an autosomal- there is, therefore, less significant typical. Palatal abnormalities may be dominant condition; a mutation in the exorbitism and malocclusion. Like present and include narrowing, bifid TWIST gene is responsible. Crouzon and Apert syndromes, uvula, and cleft palate,69 and cranial sutures in Pfeiffer syndrome Carpenter Syndrome vertebral fusion abnormalities (most may progressively fuse over time. The commonly involving C5-C6) may be Carpenter syndrome is characterized nose is generally small with a low present.70 Structural brain by synostosis most commonly nasal bridge. Partial syndactyly of the abnormalities may be present, involving both coronal sutures and second and third fingers and/or toes including agenesis of the corpus variably others as well, with shallow are cardinal features of Pfeiffer callosum, gyral malformations, absent supraorbital ridges and flat nasal syndrome, and the distal phalanges of or defective septum pellucidum, bridge, midface, and/or mandibular the thumb and great toe are often megalencephaly, and static or hypoplasia, low-set and malformed wide. Pfeiffer syndrome is progressive ventriculomegaly. Unlike ears and a high arched palate. A transmitted as an autosomal- Crouzon syndrome, neurocognitive number of digital malformations may dominant condition with variable deficits are more common, with more occur including brachydactyly, penetrance; a mutation in the FGFR2 than one-half having subnormal IQ clinodactyly, and camptodactyly gene is responsible. scores. The most striking extracranial (medial deviation and flexion abnormality in Apert syndrome is Cohen has described 3 types of deformity of the distal phalanges, osseous and/or soft tissue syndactyly Pfeiffer syndrome.71 Type I is respectively) and polydactyly involving fingers and/or toes, characterized by typical coronal involving the toes. Cardiac particularly the second, third, and synostosis, midface hypoplasia, and malformations occur in one-half of fourth digits (Fig 14). The digits are digital malformations with normal affected individuals and include short, and broad distal phalanges may neurocognitive development. Types II septal defects, tetralogy of Fallot,

Downloaded from www.aappublications.org/news by guest on October 1, 2021 12 FROM THE AMERICAN ACADEMY OF PEDIATRICS transposition of the great vessels, and SURGICAL MANAGEMENT OF therefore, preferable, even in persistent ductus arteriosus. CRANIOSYNOSTOSIS questionable cases of Carpenter syndrome is transmitted as The evaluation and management of craniosynostosis. an autosomal-recessive condition; craniosynostosis are beyond the RAB23 There are many accepted surgical pathogenic variants in the or scope of this review, but a few general MEGF8 options for craniosynostosis that are genes are responsible. comments are helpful. Imaging of influenced by which suture(s) are suspected craniosynostosis most involved, the clinical indication, the commonly includes either plain skull Antley-Bixler Syndrome experience and expertise of the radiographs or CT scans. In general, Antley-Bixler syndrome is craniofacial surgical team, and, most plain skull radiographs are of limited importantly, the timing of the characterized by bicoronal synostosis value if craniosynostosis is strongly (in 70%) with turricephaly but with operation. It is not the intent of this suspected because CT scans will review to recommend any particular frontal bossing, midface hypoplasia likely be performed by the fl operative technique because they all with exorbitism, and a at and craniofacial team as part of surgical have their merits. depressed nasal bridge. Low-set and planning. On the other hand, dysplastic ears are a consistent obtaining a CT scan in children with Surgical techniques may include feature, and choanal atresia or low suspicion for craniosynostosis is endoscopic suturectomy with helmet stenosis is present in 80%. Limited often unnecessary. Cranial therapy, spring-assisted cranioplasty, limb mobility and a diminished range ultrasonography is used by some, and and subtotal and complete calvarial of motion involving virtually all joints, studies suggest that it is as effective vault remodeling. Advantages of phalangeal abnormalities (including as plain radiographs or CT scans in endoscopic suturectomy include fi long ngers with tapering identifying a fused suture.73 However, smaller incisions and less operative fi ngernails), radiohumeral synostosis, not all radiologists are equally time and blood loss, but correction and femoral bowing are common experienced at identifying fused should be performed early (during features as well. Impaired sutures on ultrasonography, so it is the first few months of life) and steroidogenesis and genital recommended that the provider followed by up to 12 months of abnormalities are associated features. check with the radiologist first before postoperative molding helmet Antley-Bixler syndrome is most obtaining this study. Many therapy (23 hours a day) to achieve commonly related to pathogenic craniofacial teams prefer that correction comparable to open POR variants in the gene (with providers refer these children early techniques. Spring-assisted impaired steroidogenesis) and and postpone imaging until after the cranioplasty is another surgical autosomal-recessive transmission child is seen by specialists. For adjunct that can be used, in which FGFR2 and pathogenic variants of the children with occipital DP, the spring-loaded devices are inserted gene (without impaired diagnosis is usually obvious by temporarily to help distract the steroidogenesis), with autosomal- clinical inspection, the absence of freed bones. dominant transmission. significant deformity at birth, and the absence of a retroauricular bulge; The advantages of open operative correction include more immediate Muenke Syndrome questionable cases might require neuroimaging, but these are rare. and complete correction, without the Muenke syndrome is characterized by need for extended molding helmet fusion of one or both coronal sutures The timing of surgery (and, by therapy. Disadvantages include with a broad and shallow extension, referral) is another a larger incision, longer operative supraorbital ridge and prominent important consideration. Traditional times, greater intraoperative blood forehead (bossing). Hypertelorism repairs of coronal, metopic, and loss, and, for coronal and metopic and flattened maxillae are variable frontosphenoidal synostosis are synostosis, the need to remodel the features. Hearing loss is present in generally delayed until 6 to superior orbital rim (which generally approximately one-third of patients, 10 months of age. However, the child requires that the surgery be and macrocephaly is present in with symptomatic increased ICP may performed after the infant has approximately 5%.72 Muenke require earlier repair. Moreover, reached 6 months of age so the syndrome is transmitted as an sagittal synostosis repairs and orbital rim is thick enough to hold the autosomal-dominant endoscopic approaches are surgical screws). A variety of open condition and is unusual among the performed much earlier, some as techniques exist, but surgical timing syndromic synostoses in that it early as 8 weeks of age. Delays in is important. Open sagittal synostosis involves a mutation in the referral often lead to more extensive repairs are performed much earlier FGFR3 gene. surgical repairs; early referral is, (ideally between 2 and 6 months of

Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 146, number 3, September 2020 13 age) than are metopic or coronal called positional or nonsynostotic) from above the infant’s head); the synostosis. Sagittal synostosis repair plagiocephaly (DP) or brachycephaly pinna may be rotated outward as includes a midline or paramedian (so- (DB). The incidence of DP/DB has well. Finally, there is often some called p) craniectomy coupled with been estimated at 20% to 50% in 6- anterior displacement of the a variable degree of posterior month-old children.74 It is more ipsilateral forehead. The resulting (parietal and occipital) vault common (approximately 60% of deformation results in reconstruction with barrel stave cases) in male children.75 DP/DB in a parallelogram head shape (Fig 15A) osteotomies. Later surgery (generally 80% of cases presents as an acquired in which the entire ipsilateral head beyond 6–8 months of age) may postnatal condition that is most appears to have been displaced require a more extensive total commonly noted during the first 4 to anteriorly. In contrast, the child with calvarial vault remodeling. Lambdoid 12 postnatal weeks, although 20% of unilateral coronal or lambdoid suture repair is also, generally, cases appear to be noted at birth, synostosis will have a trapezoidal- performed early. In contrast, for open likely attributable to intrauterine shaped head with ipsilateral coronal or metopic synostosis, in forces (relative fetal restraint, such as flattening of both frontal and occipital which both cranial and orbital primiparity, oligohydramnios, calvarium and posterior and inferior reconstruction are performed, later multiple gestation, or bicornuate deviation of the ipsilateral ear, as surgical correction, usually between 6 uterus).75 Eighty percent of cases are discussed above. Patients with DP and 10 months, is preferred so that right sided, and the flattening may have an element of facial the orbital rim is thick enough to hold corresponds to the side to which the scoliosis (Fig 15B). Although the the surgical constructs used to infant naturally turns the head; this ipsilateral orbit in DP may be slightly advance and remodel the bone. All correlates well with observations misshapen, the Harlequin orbit open surgical approaches involve made by Volpe76 that normal supine deformity observed in unicoronal a full release of the fused suture and infants look toward the right 80% of synostosis is not present. Similarly, immediate surgical remodeling of the the time, toward the left 20%, and the bulging retromastoid area in skull; postoperative helmeting is not almost never look straight up. In lambdoid synostosis is absent in DP routinely used after open repair. addition, 15% to 20% of infants with and DB. In DB, the occiput is flattened DP/DB have some degree of neck bilaterally, and the head is, therefore, The surgical management of midface muscle imbalance or torticollis.75 It is brachycephalic and widened in the hypoplasia deserves special mention now apparent that DP/DB is not transverse dimension, leading to because it is a frequent component of synostotic but rather is caused by a round face. However, the absence of syndromic synostosis. Severe midface persistent pressure on the skull in the turricephaly, orbital retrusion, hypoplasia can lead to airway supine infant. The incidence Harlequin orbit, and exophthalmos obstruction that requires an increased significantly after the differentiate DB from bicoronal immediate intervention, such as 1992 “Back to Sleep” campaign, synostosis. a tracheostomy to secure the airway. which recommended supine sleep Definitive midface correction is (although the decreased rate of Other abnormalities observed in usually performed when the child is sudden unexpected death in infancy some cases with DP include an older (6–8 years or more) and is certainly supports the continued element of facial scoliosis. Some have usually accomplished by using endorsement of this strategy).74 elevation and shortening of the distraction osteogenesis, in which the mandible with a “hollow” space in the midface is surgically separated from It is important to differentiate DP/DB submandibular region, superficially the skull base and distraction plates from true coronal or lambdoid resembling hemifacial microsomia. are applied to the maxillary bones. By craniosynostosis. The majority of This variant seems to be more using distraction screws that are cases can be readily identified by the common among those whose DP is turned by the patient or family on history (as described above) and present at birth and/or those with a daily basis, the midface is slowly clinical examination. The infant is torticollis; it is suggested that advanced forward, and bone grows in examined from the front, back, and, perhaps the shoulder may lie within the intervening gap, much like an most importantly, top of the head. this hollow and restrict neck rotation Ilizarov procedure accomplishes for DP/DB is characterized by occipital in utero. Another less common long bones. flattening: unilaterally in DP (Fig 15) variant of DP is what is referred to as and bilaterally in DB. The ipsilateral the “Gumby” head shape in which, OCCIPITAL (DEFORMATIONAL) ear is deviated anteriorly with respect when viewed from the front, the PLAGIOCEPHALY AND BRACHYCEPHALY to the contralateral side (which can ipsilateral calvarium is flattened and The most common head shape be most readily identified by placing the vertex slopes upward toward the abnormality is deformational (also a finger in each ear and looking down opposite side (Fig 15B).

Downloaded from www.aappublications.org/news by guest on October 1, 2021 14 FROM THE AMERICAN ACADEMY OF PEDIATRICS FIGURE 15 Occipital deformational flattening (plagiocephaly and brachycephaly). A, Vertex view of DP shows parallelogram-shaped head with ipsilateral flattening, anterior deviation of the ipsilateral ear, and mildly prominent ipsilateral frontal bossing. B, Frontal view shows the calvarium deviated toward the right but no elevated eyebrow and/or orbit or deviation of the nasal root or tip. Note the upward slanting cranial vault from patient’s left to right (“Gumby” deformity). C, Posterior view of DP shows flattened right occiput with parietal boss.

A number of centers quantify the (Fig 16). In general, a CVAI of .3.5 is both described above. In most cases, severity of DP and DB, both for the consistent with DP.74 The severity of the diagnosis of DP or DB is readily initial assessment and at subsequent DB is described by using the cranial apparent on clinical examination, and follow-up visits, by measuring certain index (CI), which measures the ratio adjunctive imaging such as plain anthropometric indices with cranial of head width to head length when radiographis or CT scans is calipers. The severity of DP is viewed from above. A CI of $85% is unnecessary and would expose the described by using the cranial vault consistent with brachycephaly.77 child to ionizing radiation. The use of asymmetry index (CVAI), which imaging should be reserved for describes the difference between the The differential diagnosis of DP equivocal cases. Plain radiographs are longest and shortest head axes along includes unilateral coronal and usually difficult to interpret, except in the diagonal when viewed from above unilateral lambdoid craniosynostosis, cases of DB in which the occipital flattening is evident on lateral films. Partial nonvisualization or focal areas of calcification adjacent to the lambdoid suture may be identified on plain radiographs and CT scans but should not be interpreted as lambdoid synostosis. Axial CT scans readily differentiate DP and DB from coronal synostosis, demonstrating the parallelogram head shape, open coronal sutures, and normally formed anterior skull base with normal sphenoid wing and absent Harlequin orbit.

It is not our intent with this report to discuss treatment options for DP and DB. However, the parents of infants FIGURE 16 with DP or DB should be reassured Diagram showing the calculation of the (A) CVAI and (B) CI. See text for definitions. that since the infant does not have

Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 146, number 3, September 2020 15 craniosynostosis, surgery is not closure, with the fontanelle closing with both autosomal-dominant and indicated; they should be counseled between 4 and 26 months.85 recessive inheritance patterns have that DP and DB are solely aesthetic Moreover, it is important to note that been described. Other conditions are conditions, with no credible medical closure of the fontanelle does not usually identified by history, physical evidence suggesting that DP and DB mean that the sutures are closed, nor examination, and/or neuroimaging. affect brain development or cause any does it mean that further calvarial Important considerations include other medical condition. The head growth is not possible. Rather, closure a family history of microcephaly, the shape often improves as the child of the fontanelle simply reflects the presence or absence of gains developmental milestones and apposition of the 2 frontal and 2 developmental delays or cognitive lies less frequently on the flattened parietal bones in such a manner that impairment, and a past history of pre- side.74 Supervised “tummy time” as a gap cannot be palpated, although or postnatal brain injury. Infants with well as varying head positions while sutures are still present. In fact, even normal developmental milestones, no holding the child can help; alternating after normal fontanelle closure, past history of brain injury, and head positions for sleep can be significant head growth continues a normal head shape most often have attempted, but, to reduce the throughout childhood. As long as constitutional microcephaly. Single- incidence of sudden unexplained appropriate head growth is occurring suture craniosynostosis virtually death in infancy, it should be along the normal head growth curve never causes significant emphasized that the infant should and the head shape is normal, there microcephaly, although multisutural sleep alone, on his or her back, and in should not be concern for synostosis can. Craniosynostosis is a crib (the ABCs of safe sleep). A craniosynostosis. However, other rarely a cause of microcephaly in recent study noted a correlation (not medical conditions can be associated infants whose head circumferences, necessarily causal) between DP and with premature fontanelle closure, although low, are running parallel to poorer cognitive outcomes78; children including hyperthyroidism, the normal curve and who have both with DP should, therefore, be hyperparathyroidism, a normal head shape and no family monitored for possible hypophosphatasia, and rickets. history of craniosynostosis.86 developmental delays. The child with muscular neck imbalance or Microcephaly is defined as a head CONCLUSIONS torticollis may be referred to physical circumference below the fifth therapy to teach the parents percentile for age. There are Single-suture craniosynostosis stretching and muscle strengthening numerous causes for microcephaly, produces consistent head shape exercises to reduce the tension of the some of which are listed in Table 3. abnormalities that should be readily sternocleidomastoid muscle and Primary microcephaly may be identifiable by the pediatric health improve the strength of contralateral genetic; multiple pathogenic variants care provider. Sagittal synostosis muscles. Use of a molding helmet may produces an elongated head be considered for the infant with TABLE 3 Conditions Causing Microcephaly (scaphocephaly), and metopic a moderate or severe deformity but is synostosis produces a triangular- Primary microcephaly not required; a detailed evidence- Chromosomal disorders shaped forehead (sometimes with based review of DP and DB treatment Anencephaly hypotelorism). Unilateral coronal and options can be found in a recent Encephalocele lambdoid synostosis as well as publication by the Congress of Holoprosencephaly occipital DP all produce an Neurological Surgeons and is Agenesis of the corpus callosum asymmetric head shape Neuronal migration disorders endorsed by the American Academy Microcephaly vera (plagiocephaly) but are readily 79–84 of Pediatrics. Secondary microcephaly differentiated by the shape of the Intrauterine infections head (parallelogram versus trapezoid Intrauterine toxins or rhombus), the position of the ears EARLY FONTANELLE CLOSURE AND fi Intrauterine vascular insuf ciency (anterior or posterior), and secondary MICROCEPHALY Hypoxic-ischemic brain injury Intracranial hemorrhage features such as nasal deviation, Two other common referrals to Neonatal infections (meningitis and orbital asymmetry, or bulging of the craniofacial clinics are concerns about encephalitis) retromastoid region. Bilateral coronal early closure of the anterior Neonatal stroke and lambdoid synostosis produce fontanelle and microcephaly. Chronic cardiopulmonary or renal disease a short head (brachycephaly) and are Malnutrition Although the anterior fontanelle most Craniosynostosis differentiated by the presence or commonly closes at approximately absence of associated midface Adapted from Pina-Garza J. Fenichel’s Clinical Pediatric 12 months of age, there is a wide Neurology. 2nd ed. Amsterdam, Netherlands: Elsevier; hypoplasia or bilateral retromastoid variation in the timing of fontanelle 2013:359. bulging.

Downloaded from www.aappublications.org/news by guest on October 1, 2021 16 FROM THE AMERICAN ACADEMY OF PEDIATRICS DP and DB are the most common torticollis, should be taught neck LEAD AUTHORS head shape abnormalities stretching exercises and/or referred Mark S. Dias, MD, FAAP, FAANS encountered by primary care to a physical therapist. For those with Thomas Samson, MD, FAAP physicians; they are readily identified moderate or severe deformities, Elias B. Rizk, MD, FAAP, FAANS by conducting a history and clinical consider a referral to craniofacial Lance S. Governale, MD, FAAP, FAANS Joan T. Richtsmeier, PhD examination and do not usually specialists to discuss molding require adjunctive imaging. Early helmets. detection and positional changes SECTION ON NEUROLOGIC SURGERY EXECUTIVE COMMITTEE, 2018–2019 (with physical therapy for those with KEY POINTS torticollis) suffice for most infants; Philip R. Aldana, MD, FAAP, Chairperson referral at 5 to 6 months of age is Children with craniosynostosis most Douglas L. Brockmeyer, MD, FAAP considered for helmet therapy for commonly present with Andrew H. Jea, MD, FAAP John Ragheb, MDGregory W. Albert, MD, those who have moderate or severe stereotypically shaped heads, each associated with particular sutural MPH, FAAP deformities that have not responded Sandi K. Lam, MD, MBA, FAAP, FACS to treatment.87 fusions: Ann-Christine Duhaime, MD, FAANS Because both single-suture long (scaphocephaly: sagittal); craniosynostosis and DP/DB can short (brachycephaly: bicoronal or SECTION ON PLASTIC AND RECONSTRUCTIVE usually be diagnosed on clinical bilambdoid); SURGERY EXECUTIVE COMMITTEE, 2018–2019 examination, routine imaging for the anteriorly pointed (trigonocephaly: initial evaluation of infant head shape metopic); and Jennifer Lynn Rhodes, MD, FAAP, FACS, is not recommended to avoid Chairperson asymmetric (plagiocephaly: unilateral Stephen B. Baker, MD, DDS, FAAP, FACS, exposing the child to unnecessary coronal or lambdoid). Immediate Past Chairperson radiation. Instead, timely referral of DP and DB are the most common Anand R. Kumar, MD, FAAP, FACS infants with craniosynostosis and Jugpal Arneja, MD, FAAP those with moderate or severe DP/DB head shape abnormalities, Karl Bruckman, MD, DDS to an experienced craniofacial team recognized by their parallelogram- Lorelei J. Grunwaldt, MD, FAAP, FACS Timothy W. King, MD, PhD, FAAP, FACS (including both a pediatric shaped head, lack of retroauricular bulge, and, in 80%, absence of Arin K. Greene, MD, MMSc, FAAP neurosurgeon and craniofacial John A. Girotto, MD, FAAP, FACS surgeon) will allow sufficient time for deformation at birth. the team to help the family cope with Syndromic craniosynostosis most the diagnosis, obtain any necessary commonly manifests with imaging for surgical planning, discuss bicoronal synostosis, midface ABBREVIATIONS hypoplasia, and shallow orbits with treatment options, and plan a timely AP: anterior-posterior exorbitism and strabismus. correction. BMP: bone morphogenetic factor Anticipatory guidance for parents of Surgery is often performed within the CI: cranial index fi children with craniosynostosis should rst 8 to 10 weeks for sagittal CT: computed tomography include monitoring for symptoms of synostosis repairs, endoscopic CVAI: cranial vault asymmetry elevated ICP or developmental delays, procedures, and raised ICP. index especially for those with multisutural Orbitofrontal advancements for DB: deformational brachycephaly synostosis, and a discussion about the coronal and metopic synostosis are DP: deformational plagiocephaly importance of early and timely most often performed between 6 FGFR: fibroblast growth factor referral to specialists. Parents of and 10 months. receptor children with DP or DB should be Early referrals to craniofacial teams FGR: fibroblast growth factor encouraged to initiate positional are encouraged to allow early ICP: intercranial pressure changes early and, for those with identification and repair.

FINANCIAL DISCLOSURE: The authors have indicated they have no financial relationships relevant to this article to disclose. FUNDING: No external funding. This document is copyrighted and is property of the American Academy of Pediatrics and its Board of Directors. All authors have filed 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. POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 146, number 3, September 2020 17 REFERENCES 1. Hall BK. Endoskeleton/exo (dermal) 11. Beederman M, Farina EM, Reid RR. 21. Ornitz DM, Marie PJ. FGF signaling skeleton – mesoderm/neural crest: two Molecular basis of cranial suture pathways in endochondral and pair of problems and a shifting biology and disease: osteoblastic and intramembranous bone development paradigm. J Appl Ichthyol. 2014;30(4): osteoclastic perspectives. Genes Dis. and human genetic disease. Genes Dev. 608–615 2014;1(1):120–125 2002;16(12):1446–1465 2. Kawasaki K, Richtsmeier JT. Association 12. Da Costa AC, Walters I, Savarirayan R, 22. Wang Y, Sun M, Uhlhorn VL, et al. of the Chondrocranium and Anderson VA, Wrennall JA, Meara JG. Activation of p38 MAPK pathway in the Dermatocranium in Early Skull Intellectual outcomes in children and skull abnormalities of Apert syndrome Development. In: Percival CJ, adolescents with syndromic and Fgfr2(1P253R) mice. BMC Dev Biol. Richtsmeier JT, eds. Building Bones: nonsyndromic craniosynostosis. Plast 2010;10:22 Bone Development and Formation in Reconstr Surg. 2006;118(1): 23. Wang Y, Xiao R, Yang F, et al. Anthropology. Cambridge Studies in 175–181–183 Biological and Evolutionary Abnormalities in cartilage and bone Anthropology. Cambridge, United 13. Wilkie AOM, Byren JC, Hurst JA, et al. development in the Apert syndrome 1 Kingdom: Cambridge University Press; Prevalence and complications of single- FGFR2( /S252W) mouse. Development. – 2017:52–78 gene and chromosomal disorders in 2005;132(15):3537 3548 craniosynostosis. Pediatrics. 2010; 24. Wang Y, Zhou X, Oberoi K, et al. p38 3. Flaherty K, Singh N, Richtsmeier JT. 126(2). Available at: www.pediatrics. Inhibition ameliorates skin and skull Understanding craniosynostosis as org/cgi/content/full/126/2/e391 a growth disorder. Wiley Interdiscip Rev abnormalities in Fgfr2 Beare-Stevenson Dev Biol. 2016;5(4):429–459 14. Cunningham ML, Seto ML, Ratisoontorn mice. J Clin Invest. 2012;122(6): C, Heike CL, Hing AV. Syndromic 2153–2164 4. Nagata M, Nuckolls GH, Wang X, et al. craniosynostosis: from history to 25. Chen L, Li D, Li C, Engel A, Deng C-X. A The primary site of the acrocephalic hydrogen bonds. Orthod Craniofac Res. Ser252Trp [corrected] substitution in feature in Apert Syndrome is a dwarf 2007;10(2):67–81 cranial base with accelerated mouse fibroblast growth factor chondrocytic differentiation due to 15. Heuzé Y, Holmes G, Peter I, Richtsmeier receptor 2 (Fgfr2) results in aberrant activation of the FGFR2 JT, Jabs EW. Closing the gap: genetic craniosynostosis. [published correction signaling. Bone. 2011;48(4):847–856 and genomic continuum from appears in Bone. 2005;37(6):876]. Bone. syndromic to nonsyndromic 2003;33(2):169–178 5. Abramson DL, Janecka IP, Mulliken JB. craniosynostoses. Curr Genet Med Rep. Abnormalities of the cranial base in 26. Zhou YX, Xu X, Chen L, Li C, Brodie SG, 2014;2(3):135–145 synostotic frontal plagiocephaly. Deng C-X. A Pro250Arg substitution in J Craniofac Surg. 1996;7(6):426–428 16. Orr-Urtreger A, Bedford MT, Burakova T, mouse Fgfr1 causes increased et al. Developmental localization of the expression of Cbfa1 and premature 6. Burdi AR, Kusnetz AB, Venes JL, splicing alternatives of fibroblast fusion of calvarial sutures. Hum Mol Gebarski SS. The natural history and growth factor receptor-2 (FGFR2). Dev Genet. 2000;9(13):2001–2008 pathogenesis of the cranial coronal Biol. 1993;158(2):475–486 ring articulations: implications in 27. Yin L, Du X, Li C, et al. A Pro253Arg understanding the pathogenesis of the 17. Orr-Urtreger A, Givol D, Yayon A, Yarden mutation in fibroblast growth factor Crouzon craniostenotic defects. Cleft Y, Lonai P. Developmental expression of receptor 2 (Fgfr2) causes skeleton Palate J. 1986;23(1):28–39 two murine fibroblast growth factor malformation mimicking human Apert fl 7. Kawasaki K, Richtsmeier JT. Spatial receptors, g and bek. Development. syndrome by affecting both – association of the dermatocranium 1991;113(4):1419 1434 chondrogenesis and osteogenesis. Bone. 2008;42(4):631–643 with the chondrocranium in early skull 18. Rice DPC, Rice R, Thesleff I. Fgfr mRNA formation. Am J Phys Anthropol. 2014; isoforms in craniofacial bone 28. Eswarakumar VP, Horowitz MC, Locklin 153(S58):156 development. Bone. 2003;33(1):14–27 R, Morriss-Kay GM, Lonai P. A gain-of- function mutation of Fgfr2c 8. McBratney-Owen B, Iseki S, Bamforth 19. Delezoide AL, Benoist-Lasselin C, Legeai- demonstrates the roles of this receptor SD, Olsen BR, Morriss-Kay GM. Mallet L, et al. Spatio-temporal variant in osteogenesis. Proc Natl Acad Development and tissue origins of the expression of FGFR 1, 2 and 3 genes Sci U S A. 2004;101(34):12555–12560 mammalian cranial base. Dev Biol. during human embryo-fetal – 2008;322(1):121 132 ossification. Mech Dev. 1998;77(1):19–30 29. Mai S, Wei K, Flenniken A, et al. The missense mutation W290R in Fgfr2 9. Jiang X, Iseki S, Maxson RE, Sucov HM, 20. Bansal R, Lakhina V, Remedios R, Tole S. causes developmental defects from Morriss-Kay GM. Tissue origins and Expression of FGF receptors 1, 2, 3 in aberrant IIIb and IIIc signaling. Dev Dyn. interactions in the mammalian skull the embryonic and postnatal mouse – 2010;239(6):1888–1900 vault. Dev Biol. 2002;241(1):106 116 brain compared with Pdgfralpha, Olig2 10. Opperman LA. Cranial sutures as and Plp/dm20: implications for 30. Twigg SRF, Healy C, Babbs C, et al. intramembranous bone growth sites. oligodendrocyte development. Dev Skeletal analysis of the Fgfr3(P244R) Dev Dyn. 2000;219(4):472–485 Neurosci. 2003;25(2–4):83–95 mouse, a genetic model for the Muenke

Downloaded from www.aappublications.org/news by guest on October 1, 2021 18 FROM THE AMERICAN ACADEMY OF PEDIATRICS craniosynostosis syndrome. Dev Dyn. Foundations and Surgical Treatment of J Med Genet A. 2010;152A(12): 2009;238(2):331–342 Craniosynostosis. Baltimore, MD: 3007–3015 Williams & Wilkins; 1989:263–274 31. Holmes G, O’Rourke C, Motch Perrine 52. Persing J, Jane JA, Edgerton MT. SM, et al. Midface and upper airway 41. Gault DT, Renier D, Marchac D, Jones Surgical Treatment of Craniosynostosis. dysgenesis in FGFR2-related BM. Intracranial pressure and In: Persing J, Edgerton MT, Jane JA, eds. craniosynostosis involves multiple intracranial volume in children with Scientific Foundations and Surgical tissue-specific and cell cycle effects. craniosynostosis. Plast Reconstr Surg. Treatment of Craniosynostosis. Development. 2018;145(19):dev166488 1992;90(3):377–381 Baltimore, MD: Williams & Wilkins; 1989: 117–238 32. Ting M-C, Wu NL, Roybal PG, et al. EphA4 42. Renier D, Sainte-Rose C, Marchac D, as an effector of Twist1 in the guidance Hirsch JF. Intracranial pressure in 53. Boulet SL, Rasmussen SA, Honein MA. A of osteogenic precursor cells during craniostenosis. J Neurosurg. 1982; population-based study of calvarial bone growth and in 57(3):370–377 craniosynostosis in metropolitan craniosynostosis. Development. 2009; Atlanta, 1989-2003. Am J Med Genet A. 43. Blount JP, Louis RG Jr., Tubbs RS, Grant 136(5):855–864 2008;146A(8):984–991 JH. Pansynostosis: a review. Childs Nerv 33. Rice DP, Aberg T, Chan Y, et al. Syst. 2007;23(10):1103–1109 54. van der Meulen J, van der Hulst R, van Integration of FGF and TWIST in calvarial Adrichem L, et al. The increase of 44. Judy BF, Swanson JW, Yang W, et al. bone and suture development. metopic synostosis: a pan-European Intraoperative intracranial pressure Development. 2000;127(9):1845–1855 observation. J Craniofac Surg. 2009; monitoring in the pediatric 20(2):283–286 34. Merrill AE, Bochukova EG, Brugger SM, craniosynostosis population. et al. Cell mixing at a neural crest- J Neurosurg Pediatr. 2018;22(5): 55. Kolar JC. An epidemiological study of mesoderm boundary and deficient 475–480 nonsyndromal craniosynostoses. ephrin-Eph signaling in the J Craniofac Surg. 2011;22(1):47–49 pathogenesis of craniosynostosis. Hum 45. Arnaud E, Renier D, Marchac D. Mol Genet. 2006;15(8):1319–1328 Prognosis for mental function in 56. Lajeunie E, Le Merrer M, Bonaïti-Pellie C, scaphocephaly. J Neurosurg. 1995; Marchac D, Renier D. Genetic study of 35. Tischfield MA, Robson CD, Gilette NM, 83(3):476–479 scaphocephaly. Am J Med Genet. 1996; et al. Cerebral vein malformations 62(3):282–285 result from loss of Twist1 expression 46. Gewalli F, da Silva Guimarães-Ferreira and BMP signaling from skull JP, Sahlin P, et al. Mental development 57. Cornelissen M, Ottelander B, Rizopoulos progenitor cells and dura. Dev Cell. after modified p procedure: dynamic D, et al. Increase of prevalence of 2017;42(5):445.e5-461.e5 cranioplasty for sagittal synostosis. Ann craniosynostosis. J Craniomaxillofac Plast Surg. 2001;46(4):415–420 Surg. 2016;44(9):1273–1279 36. Holmes G. The role of vertebrate models in understanding 47. Patel A, Yang JF, Hashim PW, et al. The 58. Gallagher ER, Evans KN, Hing AV, craniosynostosis. Childs Nerv Syst. impact of age at surgery on long-term Cunningham ML. Bathrocephaly: a head 2012;28(9):1471–1481 neuropsychological outcomes in shape associated with a persistent sagittal craniosynostosis. Plast mendosal suture. Cleft Palate Craniofac 37. Martínez-Abadías N, Motch SM, Reconstr Surg. 2014;134(4):608e–617e J. 2013;50(1):104–108 Pankratz TL, et al. Tissue-specific responses to aberrant FGF signaling in 48. Toth K, Collett B, Kapp-Simon KA, et al. 59. Shah MN, Kane AA, Petersen JD, Woo AS, complex head phenotypes. Dev Dyn. Memory and response inhibition in Naidoo SD, Smyth MD. Endoscopically 2013;242(1):80–94 young children with single-suture assisted versus open repair of sagittal craniosynostosis. Child Neuropsychol. craniosynostosis: the St. Louis 38. Starr JR, Collett BR, Gaither R, et al. 2008;14(4):339–352 Children’s Hospital experience. Multicenter study of neurodevelopment J Neurosurg Pediatr. 2011;8(2):165–170 in 3-year-old children with and without 49. Starr JR, Kapp-Simon KA, Cloonan YK, single-suture craniosynostosis. Arch et al. Presurgical and postsurgical 60. Jimenez DF, Barone CM. Endoscopic Pediatr Adolesc Med. 2012;166(6): assessment of the neurodevelopment technique for sagittal synostosis. Childs 536–542 of infants with single-suture Nerv Syst. 2012;28(9):1333–1339 craniosynostosis: comparison with 39. Knight SJ, Anderson VA, Spencer-Smith 61. Vu HL, Panchal J, Parker EE, Levine NS, controls. J Neurosurg. 2007;107(2 MM, Da Costa AC. Neurodevelopmental Francel P. The timing of physiologic Suppl):103–110 outcomes in infants and children with closure of the metopic suture: a review single-suture craniosynostosis: 50. Mathijssen I, Arnaud E, Lajeunie E, of 159 patients using reconstructed 3D a systematic review. Dev Neuropsychol. Marchac D, Renier D. Postoperative CT scans of the craniofacial region. 2014;39(3):159–186 cognitive outcome for synostotic frontal J Craniofac Surg. 2001;12(6):527–532 plagiocephaly. J Neurosurg. 2006;105(1 40. Renier D. Intracranial Pressure in 62. Sauerhammer TM, Oh AK, Boyajian M, Suppl):16–20 Craniosynostosis: Pre- and et al. Isolated frontosphenoidal Postoperative Recordings. Correlation 51. Melville H, Wang Y, Taub PJ, Jabs EW. synostosis: a rare cause of synostotic with Function Results. In: Persing JA, Genetic basis of potential therapeutic frontal plagiocephaly. J Neurosurg Edgerton MT, Jane JA, eds. Scientific strategies for craniosynostosis. Am Pediatr. 2014;13(5):553–558

Downloaded from www.aappublications.org/news by guest on October 1, 2021 PEDIATRICS Volume 146, number 3, September 2020 19 63. Plooij JM, Verhamme Y, Bergé SJ, van 7097/muenke-syndrome. Accessed 81. Klimo P Jr., Lingo PR, Baird LC, et al. Lindert EJ, Borstlap-Engels VMF, September 15, 2018 Congress of Neurological Surgeons Borstlap WA. Unilateral 73. Rozovsky K, Udjus K, Wilson N, systematic review and evidence-based craniosynostosis of the Barrowman NJ, Simanovsky N, Miller E. guideline on the management of frontosphenoidal suture: a case report Cranial ultrasound as a first-line patients with positional plagiocephaly: Neurosurgery and a review of literature. imaging examination for the role of repositioning. . – J Craniomaxillofac Surg. 2009;37(3): craniosynostosis. Pediatrics. 2016; 2016;79(5):E627 E629 162–166 137(2):e20152230 82. Mazzola C, Baird LC, Bauer DF, et al. 64. Tay T, Martin F, Rowe N, et al. Prevalence 74. Roby BB, Finkelstein M, Tibesar RJ, Congress of Neurological Surgeons and causes of visual impairment in Sidman JD. Prevalence of positional systematic review and evidence-based craniosynostotic syndromes. Clin Exp plagiocephaly in teens born after the guideline for the diagnosis of patients Ophthalmol. 2006;34(5):434–440 “Back to Sleep” campaign. Otolaryngol with positional plagiocephaly: the role 65. Khan SH, Nischal KK, Dean F, Hayward Head Neck Surg. 2012;146(5):823–828 of imaging. Neurosurgery. 2016;79(5): RD, Walker J. Visual outcomes and E625–E626 75. Robinson S, Proctor M. Diagnosis and amblyogenic risk factors in management of deformational 83. Tamber MS, Nikas D, Beier A, et al. craniosynostotic syndromes: a review plagiocephaly. J Neurosurg Pediatr. Congress of Neurological Surgeons of 141 cases. Br J Ophthalmol. 2003; – systematic review and evidence-based – 2009;3(4):284 295 87(8):999 1003 guideline on the role of cranial molding 76. Volpe JJ. Neurology of the Newborn. 66. Wilkie AOM, Johnson D, Wall SA. Clinical orthosis (helmet) therapy for patients Philadelphia, PA: W.B. Saunders genetics of craniosynostosis. Curr Opin with positional plagiocephaly. Company; 1995 Pediatr. 2017;29(6):622–628 Neurosurgery. 2016;79(5):E632–E633 77. Dvoracek LA, Skolnick GB, Nguyen DC, 67. Wang JC, Nagy L, Demke JC. Syndromic 84. Tamber MS, Nikas D, Beier A, et al. et al. Comparison of traditional versus craniosynostosis. Facial Plast Surg Clin Congress of Neurological Surgeons normative cephalic index in patients North Am. 2016;24(4):531–543 systematic review and evidence-based with sagittal synostosis: measure of guideline on the role of cranial molding 68. Reddy K, Hoffman H, Armstrong D. scaphocephaly and post-operative orthosis (helmet) therapy for patients Delayed and progressive multiple outcome. Plast Reconstr Surg. 2015; with positional plagiocephaly. suture craniosynostosis. Neurosurgery. 136(3):541–548 1990;26(3):442–448 Neurosurgery. 2016;79(5):E632–E633 78. Collett BR, Wallace ER, Kartin D, 69. Kreiborg S, Cohen MM Jr.. The oral Cunningham ML, Speltz ML. Cognitive 85. Aisenson MR. Closing of the anterior manifestations of Apert syndrome. outcomes and positional plagiocephaly. fontanelle. Pediatrics. 1950;6(2): J Craniofac Genet Dev Biol. 1992;12(1): Pediatrics. 2019;143(2):e20182373 223–226 41–48 79. Baird LC, Klimo P Jr., Flannery AM, et al. 86. Hoffman HJ, Reddy KV. Progressive 70. Thompson DN, Slaney SF, Hall CM, Shaw Congress of Neurological Surgeons cranial suture stenosis in D, Jones BM, Hayward RD. Congenital systematic review and evidence-based craniosynostosis. Neurosurg Clin N Am. cervical spinal fusion: a study in Apert guideline for the management of 1991;2(3):555–564 syndrome. Pediatr Neurosurg. 1996; patients with positional plagiocephaly: 25(1):20–27 87. Flannery AM, Tamber MS, Mazzola C, the role of physical therapy. et al Summary: evidence based – 71. Cohen MM Jr.. Pfeiffer syndrome Neurosurgery. 2016;79(5):E630 E631 guidelines for the treatment of update, clinical subtypes, and 80. Flannery AM, Tamber MS, Mazzola C, pediatric positional plagiocephaly. guidelines for differential diagnosis. Am et al. Congress of Neurological Available at: https://www.cns.org/ – J Med Genet. 1993;45(3):300 307 Surgeons systematic review and Assets/2a42b91b-2146-464e-9b5c- 72. National Center for Advancing evidence-based guidelines for the c6a7c01202e2/636985419035000000/ Translational Sciences. Muenke management of patients with positional summary-with-recommendations-final- syndrome. Available at: https:// plagiocephaly: executive summary. 12-1-16-pdf Accessed September 15, rarediseases.info.nih.gov/diseases/ Neurosurgery. 2016;79(5):623–624 2018

Downloaded from www.aappublications.org/news by guest on October 1, 2021 20 FROM THE AMERICAN ACADEMY OF PEDIATRICS Identifying the Misshapen Head: Craniosynostosis and Related Disorders Mark S. Dias, Thomas Samson, Elias B. Rizk, Lance S. Governale, Joan T. Richtsmeier and SECTION ON NEUROLOGIC SURGERY, SECTION ON PLASTIC AND RECONSTRUCTIVE SURGERY Pediatrics originally published online August 31, 2020;

Updated Information & including high resolution figures, can be found at: Services http://pediatrics.aappublications.org/content/early/2020/08/27/peds.2 020-015511 References This article cites 80 articles, 11 of which you can access for free at: http://pediatrics.aappublications.org/content/early/2020/08/27/peds.2 020-015511#BIBL Permissions & Licensing Information about reproducing this article in parts (figures, tables) or in its entirety can be found online at: http://www.aappublications.org/site/misc/Permissions.xhtml Reprints Information about ordering reprints can be found online: http://www.aappublications.org/site/misc/reprints.xhtml

Downloaded from www.aappublications.org/news by guest on October 1, 2021 Identifying the Misshapen Head: Craniosynostosis and Related Disorders Mark S. Dias, Thomas Samson, Elias B. Rizk, Lance S. Governale, Joan T. Richtsmeier and SECTION ON NEUROLOGIC SURGERY, SECTION ON PLASTIC AND RECONSTRUCTIVE SURGERY Pediatrics originally published online August 31, 2020;

The online version of this article, along with updated information and services, is located on the World Wide Web at: http://pediatrics.aappublications.org/content/early/2020/08/27/peds.2020-015511

Pediatrics is the official journal of the American Academy of Pediatrics. A monthly publication, it has been published continuously since 1948. Pediatrics is owned, published, and trademarked by the American Academy of Pediatrics, 345 Park Avenue, Itasca, Illinois, 60143. Copyright © 2020 by the American Academy of Pediatrics. All rights reserved. Print ISSN: 1073-0397.

Downloaded from www.aappublications.org/news by guest on October 1, 2021