What’s New in Syndromic Craniosynostosis

Copyright © 2017 American Society of Plastic Surgeons. Unauthorized reproduction of this article is prohibited.

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The most common craniosynostosis syn-dromes are associated with mutations in the genes for fibroblast growth factor receptor

(FGFR) and TWIST family bHLH transcription factor 1 (Table 1). These syndromes can be inher-ited in an autosomal dominant manner from an

affected parent but most often result from a spo-radic de novo pathogenic mutation. In sporadic

Disclosure: The authors have no financial interest to declare in relation to the content of this article. This study did not have any funding sources.

Copyright © 2017 by the American Society of Plastic Surgeons

DOI: 10.1097/PRS.0000000000003524

Jesse A. Taylor, M.D.Scott P. Bartlett, M.D.

Philadelphia, Pa.

Learning Objectives: After studying this article, the participant should be able to: 1. Understand the role of prenatal screening and counseling of parents of unborn children with syndromic craniosynostosis. 2. Recognize the genetic ab-normalities, craniofacial phenotype, associated anomalies, and challenges associ-ated with each of the five major forms of syndromic craniosynostosis. 3. Identify the pros and cons associated with timing and types of cranial vault remodeling techniques in this patient population. 4. Understand the risks and benefits as-sociated with midface advancement with Le Fort III, Le Fort II plus zygomatic repositioning, monobloc, and facial bipartition. 5. Understand the important role of psychological counseling throughout childhood in this at-risk group.Summary: Crouzon, Apert, Pfeiffer, Muenke, and Saethre-Chotzen syndromes are the five most common forms of syndromic craniosynostosis. Although each has different genetic underpinnings and associated anomalies, their hallmark finding is turribrachycephaly most often associated with bicoronal craniosyn-ostosis. The role of prenatal screening and counseling is growing, with caregiv-ers becoming involved before birth. Multidisciplinary care from birth onward involves craniofacial plastic surgeons, neurosurgeons, otolaryngologists, oph-thalmologists, orthodontists, anesthesiologists, psychologists, speech therapists, and geneticists. Early partial, or regional, craniectomy may be urgently indi-cated in multisuture cases with signs of increased intracranial pressure. Others may be managed successfully with posterior cranial vault distraction, middle vault expansion, or fronto-orbital advancement. Some authors have advocated early monobloc advancement for those patients who require acute airway inter-vention and globe protection, although the risks of these procedures are high. Many patients will require midfacial advancement with a Le Fort III, Le Fort II plus zygomatic repositioning, monobloc, or facial bipartition. The indications, risks, and benefits for each midfacial procedure must be considered, as this step in the treatment algorithm may carry the greatest functional and aesthetic benefits but also the potential for the greatest morbidity. At the culmination of facial growth, it is not uncommon for patients to require conventional orthog-nathic surgery and other bony contouring and soft-tissue procedures. Finally, an understanding of the psychological aspects of craniofacial difference, both in affected individuals and in their families, is essential to a successful, holistic approach. (Plast. Reconstr. Surg. 140: 82e, 2017.)

From the Division of Plastic Surgery, The Children’s Hospital of Philadelphia; and the Division of Plastic Surgery, Perelman School of Medicine, University of Pennsylvania.Received for publication May 31, 2016; accepted September 8, 2016.

What’s New in Syndromic Craniosynostosis Surgery?

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Volume 140, Number 1 • Syndromic Craniosynostosis Surgery Update

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cases, advanced paternal age has been associated with de novo variants for Crouzon syndrome, Apert syndrome, Pfeiffer syndrome, and Muenke syndrome.1,2 Although many cases of craniosynos-tosis are diagnosed in the postnatal period, tech-nological advances have made prenatal diagnosis possible. Various tools used for prenatal diagnosis include imaging modalities such as two-dimen-sional ultrasound, three-dimensional ultrasound, and magnetic resonance imaging and genetic testing through both invasive and noninvasive approaches.

Fetal ultrasound can rarely enable direct visu-alization of the cranial sutures, but an experi-enced sonographer can see characteristic calvarial dysmorphology and infer the presence of prema-ture suture fusion.3 In addition, ultrasound can

be used to look for craniofacial anomalies (e.g., hypertelorism, prominent forehead, turricephaly, and depressed nasal bridge), central nervous sys-tem anomalies (e.g., ventriculomegaly and agen-esis of the corpus callosum), and limb anomalies such as the “mitten-like” syndactyly often seen with Apert syndrome.4 If ultrasound findings are suspicious for a craniosynostosis syndrome, fur-ther imaging can be pursued; three-dimensional ultrasound may provide a more detailed assess-ment of the physical anomalies noted on two-dimensional ultrasound, and magnetic resonance imaging is particularly useful for assessing central nervous system anomalies.3 Of note, ultrasound has been demonstrated to be superior to magnetic resonance imaging for visualizing musculoskeletal structures such as limb anomalies.3 Also important

Table 1. Clinical Characteristics of the Five Major Types of Syndromic Craniosynostosis Syndromes

Syndrome Gene Inheritance Craniofacial Phenotype Associated Anomalies Cognition

Crouzon FGFR2 Autosomal dominant or sporadic

Brachycephaly; shallow orbits with ocular proptosis; constricted, high-arched palate; midface hypoplasia; anterior open bite

None Normal

Apert FGFR2 Autosomal dominant possible; mostly sporadic

Turribrachycephaly; large ante-rior fontanelle with bitemporal widening and occipital flatten-ing; shallow orbits with ocular proptosis and horizontal grooves above supraorbital ridges, mild hypertelorism, and down-slanting palpebral fissures; high arched or cleft palate; severe midface hypoplasia; anterior open bite; “parrot beak” nasal deformity

Symmetric syndactyly of both hands and feet (often involving fusion of the second, third, and fourth fingers and/or toes); acne vulgaris during adoles-cence

Significantly increased incidence of intellectual disability

Pfeiffer FGFR2 Autosomal dominant or sporadic

Type I (classic Pfeiffer syndrome): turribrachycephaly; midface hypoplasia; exorbitism, hypertelorism, strabismus, down-slanting palpebral fissures; beaked nasal deformity; anterior open bite

Broad thumbs; broad great toes; variable feature, partial soft-tissue syndactyly of the hands; severe CNS involvement such as hydrocephalus (type II)

Normal or nearly normal (type I)

FGFR1 Type II: associated with kleeb-lattschädel (cloverleaf skull); severe ocular proptosis

Type III: severe ocular proptosis; shallow orbits; marked short-ness of the anterior cranial base; no kleeblattschädel (cloverleaf skull)

Muenke FGFR3 Autosomal dominant or sporadic

Craniosynostosis of coronal sutures; uncommon to have mid-face hypoplasia

Hearing loss; thimble- like middle phalanges

Increased incidence of intellectual disability

Saethre-Chotzen TWIST1 Autosomal dominant or sporadic

Heterogeneous patterns of craniosynostosis; low frontal hairline; eyelid ptosis; facial asymmetry; deviated nasal septum; ear deformities with prominent crus helicis extending through the conchal bowl; uncommon to have midface hypoplasia

Hearing loss; brachydactyly, syndactyly, and/or clinodactyly

Usually normal

CNS, central nervous system.


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Plastic and Reconstructive Surgery • July 2017

is the fact that there is a high risk of cephalopelvic disproportion, with syndromic craniosynostosis leading to high cesarean delivery rates.3

In addition to imaging studies, patients have traditionally turned to invasive procedures such as chorionic villus sampling or amniocentesis for prenatal testing. Although genetic testing for known pathogenic variants of the FGFR and TWIST1 genes can still occur through amniocen-tesis, noninvasive prenatal testing by means of the use of cell-free DNA is now possible.5 Noninvasive prenatal testing consists of analyzing the cell-free fetal DNA that is present in maternal plasma and is therefore a noninvasive blood test. Noninvasive prenatal testing was initially used to determine fetal sex and Rh blood type but has more recently been used to detect aneuploidy.5 For monogenic disorders like the majority of syndromic craniosyn-ostosis, diagnosis using cell-free DNA is possible for paternally inherited and de novo mutations but is more challenging for maternally inherited mutations because it is difficult to identify fetal maternally inherited DNA fragments from among a large excess of maternal DNA.5 Overall, nonin-vasive prenatal testing is an easy, noninvasive test that can be performed in the first trimester, and further test development may expand its clinical scope of practice.5

Different recommendations for prenatal test-ing exist for different patients. For high-risk preg-nancies that are associated with a family history of craniosynostosis, direct genetic testing can be performed if the pathogenic allele of an affected family member has been identified.6 However, for low-risk pregnancies not associated with a family history, routine fetal ultrasound can be performed. If the fetus is low-risk and does not have an abnormal head shape on ultrasound, test-ing for pathogenic variants of FGFR1, FGFR2, and FGFR3 is relatively low yield because identifying a pathogenic variant does not clarify prognosis.6 For example, a particular genetic variant may cause mild abnormality or it may cause kleeblattschädel (cloverleaf skull); in this case, the phenotypic out-come would be much more prognostically signifi-cant than the genotypic variant. Therefore, the indications for testing and the particular tests per-formed should be determined on a case-by-case basis. Regardless of the method, prenatal diagno-sis of syndromic craniosynostosis is anecdotally on the rise, with a growing number of parents seeking consultation with a craniofacial surgeon before delivery. It is important for practitioners to develop a balanced, informative, and honest approach to helping stressed, expectant parents

understand the medical, surgical, and psychoso-cial challenges of raising a child with syndromic craniosynostosis.

CRANIAL VAULT REMODELINGThe goals of cranial vault remodeling in syn-

dromic craniosynostosis are (1) to enlarge the cra-nial volume so as to optimize cerebral blood flow and prevent sequelae of intracranial pressure, and (2) to improve abnormal morphology of the skull, orbits, and upper jaw.7 Although multiple opera-tions are often needed to achieve these goals, pru-dent timing and method of intervention play key roles in minimizing the number of operations and providing the best outcome.

Timing of InterventionThe challenges of caring for children with

syndromic craniosynostosis are many, beginning when they present with severe deformities, low physiologic reserve, and significant future cranial growth.7 Early partial, or regional, craniectomy may be urgently indicated in the neonatal period in multisuture cases with signs of increased intra-cranial pressure.8

Proponents of early intervention cite the need to facilitate corneal protection and cranial expan-sion for the constricted brain.8 Conversely, the later surgery is performed, the more stable the bony correction with less need for subsequent revision.9,10 Because of different attitudes toward these challenges and a lack of rigorous outcomes data, there is significant variability in treatment approaches across craniofacial centers.

There is Level II evidence from French studies on mental development in syndromic craniosynostosis that have reported a higher intelligence quotient in patients operated on in the first year of life.11,12 This is especially true of Apert, Crouzon, and Pfeiffer syndromes and less so for Muenke syndrome.11 In 2006, Mathijssen and Arnaud provided additional Level V evidence when they polled members of the International Society of Craniofacial Surgery on this topic and found that most members agreed to initial inter-vention within the first year of life.13 More con-temporary Level III data by Utria and colleagues has narrowed the window to 6 to 9 months of age: earlier and there was a 4.1 greater odds of need-ing a major reoperation and later there was a 13.1 greater odds of needing a minor operation.14 However, their study was limited by short follow-up, limited criteria for reoperation, minimal out-comes data presented, and lack of reporting on



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types of surgery performed.14 Thus, it is difficult to draw conclusions about an optimal window of timing from the data presented by Utria et al., and further data are needed to pin down optimal tim-ing of cranial vault expansion. Timing of surgery for syndromic craniosynostosis remains controver-sial, and additional prospective comparison stud-ies are needed to adequately address this critical question.

Type of SurgeryEarly case series from multiple notable inter-

national centers reported Level IV evidence for early success with frontal expansion in syndromic craniosynostosis.15–18 However, as high-volume centers gained long-term experience with fronto-orbital advancement and cranial vault remodel-ing, some began to report high reoperation rates for both intracranial pressure and morphologic issues.19,20 Some centers have transitioned to mid-vault expansion, whereas others have migrated to the occipital region.21,22 Less invasive methods such as regional craniectomy, liberation of the occipital bone flap, and spring-mediated cra-nial vault remodeling have been demonstrated to increase cranial volume reliably in the very young.23 For example, Nowinski and colleagues performed a volumetric analysis comparing these three techniques and found expansion of 13 to 24 percent for liberation of the occipital bone flap, 18 and 25 percent for the posterior springs, and 22 to 29 percent for posterior cranial vault distraction.23 The Boston group have used early strip craniectomy and molding helmet therapy to treat a small cohort of syndromic patients.24 They performed strip craniectomy between 1 and 4 months of age and found significant improve-ment in head circumference and cranial indices with the procedure. Although greater than 50 percent of patients required additional cranial surgery within relatively short follow-up, mostly in the form of fronto-orbital advancement, their low morbidity rate of 6 percent (one cerebrospi-nal fluid leak) is cause for consideration.24

In 2009, White and colleagues published their experience with posterior cranial vault distraction, a procedure that has revolutionized how many cen-ters treat syndromic craniosynostosis.25 We have used posterior cranial vault distraction as the initial cranial remodeling procedure for many patients with syndromic synostosis since 2009 because of its superior cranial volume expansion compared with fronto-orbital advancement,24 reliability of use in early infancy,26,27 and favorable periopera-tive morbidity profile.27 It is a nondevascularizing

osteotomy, minimizing infectious risk and poten-tially preserving subsequent cranial growth poten-tial28 (Fig. 1). It provides for gradual expansion of the soft-tissue envelope, which likely minimizes relapse, and eliminates the need for indwelling hardware and bone grafting.29 We have also noted improvements in both anterior and posterior cra-nial morphology, with positive implications on turribrachycephaly29 and rates of tonsillar her-niation (unpublished). Its major limitation is the need for a second minor procedure for distractor removal.29 (See Video, Supplemental Digital Con-tent 1, which depicts performance of posterior cra-nial vault distraction on a skull model. This video is available in the “Related Videos” section of the full-text article on PRSJournal.com or at http://links.lww.com/PRS/C202. See Video, Supplemental Digital Content 2, which depicts performance of posterior cranial vault distraction on an infant with syndromic craniosynostosis. This video is available in the “Related Videos” section of the full-text arti-cle on PRSJournal.com or at http://links.lww.com/PRS/C203.)

In a head-to-head volumetric comparison of fronto-orbital advancement to posterior cranial vault distraction, we found that posterior cranial vault distraction allowed for almost twice the volu-metric gains, with similar perioperative morbid-ity.27 We have also noted the ability to delay frontal surgery, and in some patients we have eliminated fronto-orbital advancement and gone straight to a monobloc procedure at approximately age 5 years30 (Fig. 2). This preserves frontal growth, may facili-tate improved frontal morphologic changes, and increases the likelihood of optimal frontal contour over the long-term with subsequent fronto-orbital advancement.30 We recently published data show-ing that use of early posterior cranial vault distrac-tion decreases the number of major craniofacial procedures experienced in the first 5 years of life for patients with Apert syndrome, reducing expo-sure to general anesthesia and the consequences of perioperative blood loss (Level II).30

Figure 3 depicts The Children’s Hospital of Philadelphia algorithm for treating syndromic craniosynostosis with early posterior cranial vault distraction. This algorithm is further supported by Level II data from The Netherlands indicating that occipital expansion is preferred as the initial surgery in Apert and Crouzon-Pfeiffer syndromes based on its greater expansion of occipitofrontal head circumference, lower rates of tonsillar her-niation after surgery, and lower rates of papill-edema in follow-up.31 The Dutch data in a large number of patients over a significant period

http://links.lww.com/PRS/C202





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provide objective metrics by which to evaluate their conclusions.31

Even when patients have had successful expansion of the posterior vault, many will have significant frontal and orbital retrusion, fore-head dysmorphology, and turricephaly,18 prompt-ing the need for fronto-orbital advancement and cranial vault remodeling. Such a procedure per-formed in the early years of life should aim to maximally advance the supraorbital bar, normal-ize forehead shape, and decrease turricephaly.20 To maintain the correction will require the use of either resorbable plates and screws or locking/

step osteotomies and intercalated bone grafts. The ability to delay fronto-orbital advancement and cranial vault remodeling, however, with poste-rior cranial vault distraction has important impli-cations on need for reoperative frontal surgery, which becomes successively complex over time. Lastly, the role of early monobloc distraction con-tinues to be debated. Monobloc distraction may be considered in patients with severe exorbitism with a threat of a loss of vision and/or severe obstructive sleep apnea (Level III); there are no clear long-term outcomes data available about the

Fig. 1. Line drawing demonstrating the osteotomy sites and distrac-tor placement for posterior cranial vault distraction. Note the low occipital barrel-stave osteotomies that are greensticked and lagged to the distraction segment allowing for increased volume gains in the cerebellar region. (Reprinted with permission from Goldstein JA, Paliga JT, Wink JD, Low DW, Bartlett SP, Taylor JA. A craniometric anal-ysis of posterior cranial vault distraction osteogenesis. Plast Reconstr Surg. 2013;131:1367–1375.)

Video 1. Supplemental Digital Content 1, which depicts perfor-mance of posterior cranial vault distraction on a skull model. This video is available in the “Related Videos” section of the full-text article on PRSJournal.com or at http://links.lww.com/PRS/C202.

Video 2. Supplemental Digital Content 2, which depicts per-formance of posterior cranial vault distraction on an infant with syndromic craniosynostosis. This video is available in the “Related Videos” section of the full-text article on PRSJournal.com or at http://links.lww.com/PRS/C203.





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subsequent effect on growth and need for revision surgery of monobloc advancement.32,33

THE MIDFACEApert, Crouzon, and Pfeiffer syndromes are

associated with maxillary hypoplasia, exorbitism, and hypertelorism of varying degrees.34 Impor-tantly, the hypoplasia exists in the vertical, sagittal, and transverse planes, and accurate anatomical diagnosis of which planes are involved, and to what degree, help to guide selection of an operation to correct the physical and functional deformity.34 Indications for correction include acute or chronic vision impairment, obstructive sleep apnea, maloc-clusion, and appearance-related concerns.34

Timing of surgery is tailored to addressing the functional need, with surgery delayed, if pos-sible, to between 5 and 8 years of age, at which point the orbits have essentially reached physical maturity.35 Level III evidence suggests little to no vertical or sagittal growth of the maxilla after mid-face osteotomy,35–37 a risk that must be weighed against the benefits of early surgery. An important tenet of midface surgery is sagittal overcorrection,

especially when performed early. Failure to over-correct to the point of making patients appear “snouty” will likely lead to the need for further midface advancement later in life.

Osteotomy ChoiceThe choice of osteotomy for midface advance-

ment has been a source of increasing scrutiny and debate over the past decade. Important anatomical considerations include the status of the frontal bar, presence of hypertelorism, degree of exorbitism, rotational status of the orbits, nasal length, degree of central versus peripheral midfacial hypoplasia, maxillary dental arc, presence of an anterior open bite, and degree of obstructive sleep apnea37,38,39 (Fig. 3). In cases with retrusion of the frontal bar, the choice must be made between a repeated anterior cranial expansion followed by midface advancement versus monobloc osteotomy with or without facial bipartition. Proponents of separat-ing cranial expansion from midface advancement generally point to the relatively higher morbidity of combining the two40; proponents of monob-loc with or without facial bipartition point to the inherent benefits of minimizing surgical burden

Fig. 2. The Children’s Hospital of Philadelphia algorithm for management of children with syndromic craniosynostosis. (Reprinted with permission from Swanson JW, Samra F, Bauder A, Mitchell BT, Taylor JA, Bartlett SP. An algorithm for managing syndromic craniosynostosis using posterior vault distraction osteogenesis. Plast Reconstr Surg. 2016;137:829e–841e.)


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with an acceptable morbidity profile, especially when performed with distraction41 (Fig. 3).

Le Fort III OsteotomyThe Le Fort III osteotomy as described by

Gillies42 and later refined by Tessier39 is designed to move all midfacial elements—maxilla, nasal

bones, and zygoma—forward as a single unit (Figs. 3 through 5). Multiple authors have pub-lished Level III evidence of both the stability and safety of the Le Fort III procedure both by conven-tional osteotomy35,43–45 and by distraction.37,40,46–48 Distraction appears to provide for greater over-all advancement, the gradual accommodation of

Fig. 3. Options for midface osteotomy in children with syndromic craniosynostosis, which include Le Fort III, Le Fort II with zygomatic repositioning, monobloc, and monobloc with facial bipartition. The table below the line drawings provides a comparative risk-to-benefit assessment of the various options.



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periorbital and perioral soft tissues, and the ability to control the vector of movement with an exter-nal device.49 Conventional osteotomy offers the benefits of an acute advancement without subse-quent surgery for device removal. The Le Fort III procedure remains a favorable choice for most patients with Crouzon and Pfeiffer syndromes, as they lack an anterior open bite and suffer from fairly uniform midface hypoplasia at the perior-bital and dentoalveolar regions. Provided that these patients have reasonable brow position and no intracranial pressure issues, a Le Fort III pro-cedure is a reasonable choice for treating midface hypoplasia (Figs. 3 through 5).

Le Fort II Midface Distraction with Zygomatic Repositioning

Le Fort II midface distraction with zygomatic repositioning provides for differential reposi-tioning of the lateral orbitozygomatic complex from the central midface, which tends to be more hypoplastic in Apert syndrome patients.50 In Apert syndrome, “the orbits need to be advanced to improve globe protection and lat-eral profile curvature, but the central midface needs independent vertical elongation and sag-ittal rotation-advancement to improve both the worm’s eye and frontal view proportions.”50 By differing the vectors, and the amount of advance-ment and rotation, the Le Fort II midface distrac-tion with zygomatic repositioning lengthens the nose, lengthens and advances the central mid-face, closes the anterior open bite, and improves canthal tilt (Fig. 3). It can be combined with frontal contouring, as Hopper et al. have dem-onstrated in several cases, with relative safety,50 and it has been shown to “normalize facial pro-portions” better than a classic Le Fort III proce-dure in Apert syndrome.50 Shortcomings of the technique include the lack of correction of the hypertelorism and bizygomatic widening that often accompanies the Apert deformity and the use of rigid metallic plates, which may have adverse sequelae in a growing skeleton.

Monobloc Distraction with Facial BipartitionA competing surgical choice in Apert and

some Pfeiffer patients with a biconcave facial dys-morphology is the monobloc with facial biparti-tion procedure. Popularized by Greig et al. and Ponniah et al., it combines monobloc distraction with a facial bipartition to “unfurl” or “unbend” the face, improve hypertelorism, correct exor-bitism, close an anterior open bite (V-shaped),

improve canthal tilt, and decrease facial width in the middle third51,52 (Figs. 4 and 5). It allows for a greater advancement of the central midface relative to the lateral aspect, similar to the Le Fort II midface distraction with zygomatic repo-sitioning, but it does so without lengthening the central midface, a benefit in select patients and deleterious in others.53 Drawbacks of the proce-dure are its relatively higher morbidity, perhaps as high as 60 percent,54 which may include naso-cranial fistula leading to ascending infection, cerebrospinal fluid leak, loss of vision, frontal lobe injury, seizures, and velopharyngeal incom-petence.51–55 Despite a relatively higher reported morbidity, the benefits to form and function from monobloc distraction with facial biparti-tion make it a reasonable consideration in select patients (Fig. 6).

PSYCHOSOCIAL ASPECTS OF CAREThe diagnosis of a craniosynostosis-associated

syndrome has both medical implications and psy-chosocial consequences for the child and his or her caregivers. Aside from appearance, parents often wonder about their child’s future intellec-tual capabilities and behavior. Although there is some literature regarding the risk of intellectual disability with each craniosynostosis syndrome (Table 1), it is impossible to predict the future cognitive abilities for each individual child.56 In addition, children with syndromes associated with hearing loss are at increased risk for speech and language development delays.57 One study looking at children with Apert syndrome dem-onstrated that expressive and receptive language difficulties can be present in the absence of intel-lectual disabilities.57 Finally, intellectual disability has been tied to behavioral problems, with one study showing that intellectual disability increases the risk of behavioral problems by 50 to 60 per-cent.58 Recommended testing for children with syndromic craniosynostosis includes psychodiag-nostic testing at age 2 years and when entering elementary school; additional screening for learn-ing disabilities should occur at approximately 7 to 9 years of age.34

In terms of the psychosocial functioning of the child and his or her caregivers, a multidisciplinary team is required to provide support and guidance throughout the duration of treatment. In partic-ular, syndromic craniosynostosis patients are at increased risk for psychosocial issues compared with nonsyndromic craniosynostosis patients because of their increased duration of treatment,


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increased number of surgical procedures, and the increased complexity of their craniofacial anom-alies.58 Although psychosocial support should be offered throughout treatment, there are key peri-ods during which greater psychosocial awareness is required: initial diagnosis to first intervention, the time surrounding surgical procedures, and during transitional periods of the child’s devel-opment such as when entering elementary school or becoming an adolescent.58 During the time of diagnosis and primary intervention, focus should be placed on addressing parental anxieties and providing parental education. Supporting par-ents and helping them build self-confidence and acceptance is essential.58 During childhood, par-ents are faced with the challenge of choosing the appropriate school for their child.59 In addition, children and their peers may start to become aware of their appearance, leading to behavioral problems, bullying, and/or changes in personal-ity. Although addressing the child is important, it is also imperative to counsel the parents because

parental resilience influences the resilience of the child.59 As the child approaches adolescence, he or she begins to separate from his or her parents and becomes more involved in decision-making. In addition, over one-third of these patients expe-rience stigmatization because of their appear-ance32; therefore, strategic counseling of the adolescent regarding psychosocial adaptation, self-understanding, social skills, and self-image should be used.60,61 Interestingly, Raposo-Amaral and colleagues found that both the highest func-tioning Apert patients and the Crouzon patients had a satisfactory quality of life, demonstrating that these syndromic patients had acquired the necessary means with which to manage adverse daily situations of their lives.62

Throughout the course of treatment, the cra-niofacial center should provide various forms of support to patients and their parents. The avail-ability of an easily accessible clinical care coordi-nator who has expertise in both the medical and psychological aspects of care is highly valued by

Fig. 4. (Left) Anteroposterior photograph of 2-year-old girl with Crouzon syndrome. (Second from left) Lateral photograph of 2-year-old girl with Crouzon syndrome. (Second from right) Anteroposterior view of a three-dimensional computed tomographic scan. (Right) Lateral view of a three-dimensional computed tomographic scan.

Fig. 5. (Left) The same patient as shown in Figure 4, at age 9. She has undergone posterior cranial vault distraction followed by fronto-orbital advancement and cranial vault remodeling in the toddler years. She later underwent subcranial Le Fort III advance-ment with distraction that has overcorrected her deformity to give her a “snouty” appearance in anticipation of growth-related relapse. (Second from left) Lateral view. (Second from right) Anteroposterior view of a three-dimensional computed tomographic scan. (Right) Lateral view of a three-dimensional computed tomographic scan.



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patients.62 In addition, visits with a specialized social worker or therapist may be helpful during times of transition. Finally, if the patient or his or her family requires additional support, they should have access to a psychiatrist or psycholo-gist who is familiar with the challenges faced by children with syndromic craniosynostosis.

Jesse A. Taylor, M.D.Division of Plastic Surgery

The Children’s Hospital of PhiladelphiaColket Translational Research Building

3401 Civic Center BoulevardPhiladelphia, Pa. 19104

[email protected]

PATIENT CONSENTParents or guardians provided written consent for

use of the patients’ images.

ACKNOWLEDGMENTThe authors would like to thank Wen Xu for assis-

tance in preparing this article.

REFERENCES 1. Glaser RL, Jiang W, Boyadjiev SA, et al. Paternal origin of

FGFR2 mutations in sporadic cases of Crouzon syndrome and Pfeiffer syndrome. Am J Hum Genet. 2000;66:768–777.

2. Rannan-Eliya SV, Taylor IB, De Heer IM, Van Den Ouweland AM, Wall SA, Wilkie AO. Paternal origin of FGFR3 muta-tions in Muenke-type craniosynostosis. Hum Genet. 2004;115:200–207.

3. Giancotti A, D’Ambrosio V, De Filippis A, et al.; PECRAM Study Group. Comparison of ultrasound and magnetic reso-nance imaging in the prenatal diagnosis of Apert syndrome: Report of a case. Childs Nerv Syst. 2014;30:1445–1448.

4. Chen CP, Su YN, Hsu CY, et al. Second-trimester molecu-lar prenatal diagnosis of sporadic Apert syndrome follow-ing sonographic findings of mild ventriculomegaly and clenched hands mimicking trisomy 18. Taiwan J Obstet Gynecol. 2010;49:129–132.

5. Benn P. Non-invasive prenatal testing using cell free DNA in maternal plasma: Recent developments and future pros-pects. J Clin Med. 2014;3:537–565.

6. Robin N, Falk M, Haldeman-Englert C. FGFR-related cranio-synostosis syndromes. In: Pagon R, Adam M, Ardinger H, et al., eds. GeneReviews. Seattle: University of Washington; 2011.

7. Taylor JA, Derderian CA, Bartlett SP, Fiadjoe JE, Sussman EM, Stricker PA. Perioperative morbidity in posterior cranial vault expansion: Distraction osteogenesis versus conven-tional osteotomy. Plast Reconstr Surg. 2012;129:674e–680e.

Fig. 6. (Above, left) Anteroposterior photograph of a female infant with Apert syndrome. (Above, second from left) Lateral photo-graph of a female infant with Apert syndrome. (Above, second from right) Anteroposterior view of a three-dimensional computed tomographic scan. (Above, right) Lateral view of a three-dimensional computed tomographic scan. (Below, left) Anteroposterior view of Apert syndrome patient after undergoing posterior cranial vault distraction and fronto-orbital advancement and cranial vault remodeling in infancy followed by a monobloc distraction with facial bipartition at age 8. (Below, second from left) Lateral view of an Apert syndrome patient. (Below, second from right) Anteroposterior view of a computed tomographic scan. (Below, right) Lateral view of a computed tomographic scan

mailto:[email protected]


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8. Hashim PW, Patel A, Yang JF, et al. The effects of whole-vault cranioplasty versus strip craniectomy on long-term neuro-psychological outcomes in sagittal craniosynostosis. Plast Reconstr Surg. 2014;134:491–501.

9. Fearon JA. Evidence-based medicine: Craniosynostosis. Plast Reconstr Surg. 2014;133:1261–1275.

10. Fearon JA, Podner C. Apert syndrome: Evaluation of a treat-ment algorithm. Plast Reconstr Surg. 2013;131:132–142.

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What’s New in Syndromic Craniosynostosis

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