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BMJ Case Reports Oct 2010This report concerns a 20-month-old boy, born at 31 weeks of gestation, being followed in the paediatric clinic because of prematurity. He was developing appropriately...
This report concerns a 20-month-old boy, born at 31 weeks of gestation, being followed in the paediatric clinic because of prematurity. He was developing appropriately for his age and his head circumference was growing steadily (between the 75th and 90th centile), with weight and height on the 25th centile. An x-ray of his skull was performed at this stage because of his head shape, which was long and narrow (scaphocephalic)-in itself suggestive of sagittal synostosis. The x-ray confirmed the diagnosis. He was referred to a regional neurosurgical unit for further management. He had a successful surgical correction without major problems. It is to be emphasised that there is a higher morbidity and mortality if reconstructive surgery is not carried out at an early age, and therefore early diagnosis is vital in this congenital condition.
Topics: Cephalometry; Child Development; Craniosynostoses; Esthetics; Follow-Up Studies; Humans; Infant; Infant, Newborn; Infant, Premature; Male; Plastic Surgery Procedures; Risk Assessment; Skull; Tomography, X-Ray Computed; Treatment Outcome
PubMed: 22778078
DOI: 10.1136/bcr.05.2010.3026 -
Journal of Developmental and Behavioral... Oct 2005Over the past decade there has been a dramatic increase in referrals to specialty clinics, craniofacial centers, plastic surgeons, and neurosurgeons for assessment and... (Review)
Review
Over the past decade there has been a dramatic increase in referrals to specialty clinics, craniofacial centers, plastic surgeons, and neurosurgeons for assessment and treatment of deformational plagiocephaly (DP). Though considered a medically benign condition, preliminary reports suggest that DP may be associated with developmental problems. However, mechanisms to account for this association have not been hypothesized or empirically tested. Although treatment justifications often center on prevention of atypical appearance, little is known about the cosmetic outcomes of treated and untreated children. In this review we hypothesize different etiological pathways linking DP with neurodevelopment (e.g., environmental positioning limitations with and without underlying CNS pathology). We outline directions for research on incidence and prevalence, developmental outcomes, sex differences, determinants of treatment participation, and craniofacial appearance. Despite the paucity of existing research, preliminary findings suggest that children with this condition should be screened and monitored for developmental delays or deficits, as we await more conclusive information from future studies.
Topics: Cognition Disorders; Craniosynostoses; Developmental Disabilities; Female; Humans; Incidence; Infant; Male; Mass Screening; Prevalence
PubMed: 16222180
DOI: 10.1097/00004703-200510000-00008 -
Organogenesis 2012Craniosynostosis describes the premature fusion of one or more cranial sutures and can lead to dramatic manifestations in terms of appearance and functional impairment.... (Review)
Review
Craniosynostosis describes the premature fusion of one or more cranial sutures and can lead to dramatic manifestations in terms of appearance and functional impairment. Contemporary approaches for this condition are primarily surgical and are associated with considerable morbidity and mortality. The additional post-operative problems of suture refusion and bony relapse may also necessitate repeated surgeries with their own attendant risks. Therefore, a need exists to not only optimize current strategies but also to develop novel biological therapies which could obviate the need for surgery and potentially treat or even prevent premature suture fusion. Clinical studies of patients with syndromic craniosynostosis have provided some useful insights into the important signaling pathways and molecular events guiding suture fate. Furthermore, the highly conserved nature of craniofacial development between humans and other species have permitted more focused and step-wise elucidation of the molecular underpinnings of craniosynostosis. This review will describe the clinical manifestations of craniosynostosis, reflect on our understanding of syndromic and non-syndromic craniosynostoses and outline the different approaches that have been adopted in our laboratory and elsewhere to better understand the pathogenesis of premature suture fusion. Finally, we will assess to what extent our improved understanding of the pathogenesis of craniosynostosis, achieved through laboratory-based and clinical studies, have made the possibility of a non-surgical pharmacological approach both realistic and tangible.
Topics: Animals; Cranial Sutures; Craniosynostoses; Disease Models, Animal; Humans; Molecular Targeted Therapy; Morphogenesis; Signal Transduction
PubMed: 23249483
DOI: 10.4161/org.23307 -
Journal of Medical Genetics Apr 1987
Topics: Adolescent; Child; Craniosynostoses; Diagnosis, Differential; Facial Bones; Female; Humans; Infant; Limb Deformities, Congenital; Male; Nose; Skull; Syndrome; Thorax
PubMed: 3585934
DOI: 10.1136/jmg.24.4.193 -
American Journal of Audiology Jun 2014There are a number of craniosynostosis syndromes with hearing loss-including Muenke, Apert, Pfeiffer, Crouzon, Beare-Stevenson, Crouzon with acanthosis nigricans, and... (Review)
Review
PURPOSE
There are a number of craniosynostosis syndromes with hearing loss-including Muenke, Apert, Pfeiffer, Crouzon, Beare-Stevenson, Crouzon with acanthosis nigricans, and Jackson-Weiss syndromes-that result from mutations in the fibroblast growth factor receptor (FGFR) genes. Studies of FGFRs and their ligands, fibroblast growth factors (FGFs), have revealed clues to the precise contribution of aberrant FGFR signaling to inner ear morphogenesis and the hearing loss encountered in craniosynostoses. The purpose of this article is to review basic studies of FGFRs with emphasis on their function and expression in the inner ear and surrounding structures.
METHOD
A Medline search was performed to find basic science articles regarding FGFR, their ligands, and their expression and relevant mouse models. Additional items searched included clinical descriptions and studies of individuals with FGFR-related craniosynostosis syndromes.
RESULTS
The FGF signaling pathway is essential for the morphogensis and proper function of the inner ear and auditory sensory epithelium.
CONCLUSION
The variable auditory phenotypes seen in individuals with Muenke syndrome may have a genetic basis, likely due to multiple interacting factors in the genetic environment or modifying factors. Further analysis and studies of mouse models of Muenke syndrome, in particular, may provide clues to the specific effects of the defining mutation in FGFR3 in the inner ear not only at birth but also into adulthood. In particular, investigations into these models may give insight into the variable expression and incomplete penetrance of this phenotype.
Topics: Animals; Child; Craniosynostoses; Deafness; Disease Models, Animal; Genetic Therapy; Hearing Loss; Humans; Mice; Receptor, Fibroblast Growth Factor, Type 3; Receptors, Fibroblast Growth Factor; Signal Transduction; Syndrome
PubMed: 24686979
DOI: 10.1044/2014_AJA-13-0036 -
Revista Paulista de Pediatria : Orgao... Dec 2016To review the current comprehensive care for nonsyndromic craniosynostosis and nonsynostotic cranial deformity and to offer an overall view of these craniofacial... (Review)
Review
OBJECTIVE
To review the current comprehensive care for nonsyndromic craniosynostosis and nonsynostotic cranial deformity and to offer an overall view of these craniofacial conditions.
DATA SOURCE
The review was conducted in the PubMed, SciELO, and LILACS databases without time or language restrictions. Relevant articles were selected for the review.
DATA SYNTHESIS
We included the anatomy and physiology of normal skull development of children, discussing nuances related to nomenclature, epidemiology, etiology, and treatment of the most common forms of nonsyndromic craniosynostosis. The clinical criteria for the differential diagnosis between positional deformities and nonsyndromic craniosynostosis were also discussed, giving to the pediatrician subsidies for a quick and safe clinical diagnosis. If positional deformity is accurately diagnosed, it can be treated successfully with behavior modification. Diagnostic doubts and craniosynostosis patients should be referred straightaway to a multidisciplinary craniofacial center.
CONCLUSIONS
Pediatricians are in the forefront of the diagnosis of patients with cranial deformities. Thus, it is of paramount importance that they recognize subtle cranial deformities as it may be related to premature fusion of cranial sutures.
Topics: Craniofacial Abnormalities; Craniosynostoses; Humans; Infant; Pediatrics; Skull
PubMed: 27256993
DOI: 10.1016/j.rpped.2016.01.004 -
Scientific Reports Jan 2020Early fusion of the sagittal suture is a clinical condition called, sagittal craniosynostosis. Calvarial reconstruction is the most common treatment option for this...
Early fusion of the sagittal suture is a clinical condition called, sagittal craniosynostosis. Calvarial reconstruction is the most common treatment option for this condition with a range of techniques being developed by different groups. Computer simulations have a huge potential to predict the calvarial growth and optimise the management of this condition. However, these models need to be validated. The aim of this study was to develop a validated patient-specific finite element model of a sagittal craniosynostosis. Here, the finite element method was used to predict the calvarial morphology of a patient based on its preoperative morphology and the planned surgical techniques. A series of sensitivity tests and hypothetical models were carried out and developed to understand the effect of various input parameters on the result. Sensitivity tests highlighted that the models are sensitive to the choice of input parameter. The hypothetical models highlighted the potential of the approach in testing different reconstruction techniques. The patient-specific model highlighted that a comparable pattern of calvarial morphology to the follow up CT data could be obtained. This study forms the foundation for further studies to use the approach described here to optimise the management of sagittal craniosynostosis.
Topics: Child, Preschool; Computer Simulation; Cranial Sutures; Craniosynostoses; Craniotomy; Finite Element Analysis; Humans; Image Processing, Computer-Assisted; Infant; Infant, Newborn; Longitudinal Studies; Retrospective Studies; Skull; Tomography, X-Ray Computed
PubMed: 31913294
DOI: 10.1038/s41598-019-55224-5 -
American Journal of Ophthalmology Mar 2022This study is the first to evaluate the prevalence of retinal thinning and the correlation with papilledema and visual acuity (VA) in a large population with...
PURPOSE
This study is the first to evaluate the prevalence of retinal thinning and the correlation with papilledema and visual acuity (VA) in a large population with craniosynostosis.
DESIGN
Prospective clinical cohort study.
METHODS
All and complex patients syndromic and complex with craniosynostosis who visited the only national referral center between 2018 and 2020 were included. Retinal layers were segmented using optical coherence tomography. Patients were seen by an ophthalmologist for VA assessment and fundoscopy. Multivariate regression models were developed to evaluate correlations between retinal thickness, papilledema and VA.
RESULTS
We included 127 patients. Retinal thinning was most prevalent in the peripapillary retinal nerve fiber layer (≤38%). A longer duration of papilledema in early childhood correlated with an increased peripapillary retinal nerve fiber layer and total retinal thickness optic nerve head later in life (+0.3 ± 0.2, P = .04 and +1.0 ± 1.0, P = .003); however, its thickness was not correlated with the VA (P = .20 and P = .53). Macular retinal thinning was associated with a worse VA (P = .01); however, it was not correlated with the duration of papilledema (P = .95).
CONCLUSIONS
Following a preventative treatment strategy for syndromic and complex craniosynostosis, the prevalence of retinal ONH thinning is low. Although the prevalence of peripapillary retinal nerve fiber layer thinning is considerable, its thickness is not correlated with VA. In contrast, macular thinning is correlated with worse VA scores and should, therefore, be evaluated during follow-up. Future studies should evaluate the (1) causative mechanism for macular thinning, (2) correlation between the time to surgery and macular thinning, and (3) results of reactive treatment strategies and compare those results to the current study.
Topics: Child, Preschool; Cohort Studies; Craniosynostoses; Humans; Nerve Fibers; Papilledema; Prospective Studies; Retinal Ganglion Cells; Tomography, Optical Coherence; Visual Acuity
PubMed: 34487703
DOI: 10.1016/j.ajo.2021.08.014 -
JAMA Network Open Sep 2021Findings on the cognitive, behavioral, and psychological functioning of individuals with sagittal synostosis (SS) are highly disparate, limiting their clinical utility. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Findings on the cognitive, behavioral, and psychological functioning of individuals with sagittal synostosis (SS) are highly disparate, limiting their clinical utility.
OBJECTIVE
To identify and review research on individuals with SS and to determine whether, and to what extent, they experience cognitive, behavioral, and psychological difficulties compared with their healthy peers or normative data for each measure.
DATA SOURCES
PubMed, Scopus, Embase, and PsycINFO were searched through January 2021 with no date restrictions. Scopus citation searches and manual checks of the reference lists of included studies were conducted.
STUDY SELECTION
Studies included participants of any age who had received a diagnosis of single-suture (isolated or nonsyndromic) SS or scaphocephaly and who had been assessed on cognitive, behavioral, and psychological outcomes.
DATA EXTRACTION AND SYNTHESIS
Data were independently extracted by 2 reviewers. Case-control outcomes (individuals with SS vs healthy peers or normative data) were compared using random-effects models with 3 effect sizes calculated: weighted Hedges g (gw), odds ratios (ORs), and mean prevalence rates. This study follows the Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines.
MAIN OUTCOMES AND MEASURES
Findings were categorized by surgical status (conservatively managed, presurgery, postsurgery, or combined); domain (eg, general cognition); type of cognitive, behavioral, or psychological measure (objective or subjective); and source of comparison data (peers or normative data).
RESULTS
Data from 32 studies, involving a pooled sample of 1422 children and adults with SS (mean [SD] age at assessment, 5.7 [6.6] years; median [interquartile range] age, 3.3 [0.5-10.3] years), were analyzed. Data on sex were available for 824 participants, and 642 (78%) were male. Individual study results varied substantially. Objective tests identified significant moderate group differences on 3 of 16 examined domains: presurgical motor functioning (3 studies; gw = -0.42; 95% CI, -0.67 to -0.18; P < .001), postsurgical short-term memory (2 studies; gw = -0.45; 95% CI, -0.72 to -0.17; P < .001), and postsurgical visuospatial ability (6 studies; gw = 0.31; 95% CI, 0.18 to 0.44; P < .001). Prevalence estimates and ORs varied widely, with 15 studies showing prevalence estimates ranging from 3% to 37%, and 3 studies showing ORs ranging from 0.31 (95% CI, 0.01 to 6.12) for processing speed in the conservatively managed sample to 4.55 (95% CI, 0.21 to 98.63) for postsurgical visuospatial abilities.
CONCLUSIONS AND RELEVANCE
In this meta-analysis, findings for the functioning of participants with SS were highly disparate and often of low quality, with small samples sizes and control groups rarely recruited. Nonetheless, the findings suggest that some individuals with SS experience negative outcomes, necessitating routine assessment.
Topics: Child; Child Behavior; Cognition; Cranial Sutures; Craniosynostoses; Humans; Psychometrics
PubMed: 34515785
DOI: 10.1001/jamanetworkopen.2021.21937 -
Plastic and Reconstructive Surgery May 2022Nonsyndromic craniosynostosis is one of the most common anomalies treated by craniofacial surgeons. Despite optimal surgical management, nearly half of affected children...
BACKGROUND
Nonsyndromic craniosynostosis is one of the most common anomalies treated by craniofacial surgeons. Despite optimal surgical management, nearly half of affected children have subtle neurocognitive deficits. Whereas timing and type of surgical intervention have been studied, the possibility of genetic influence on neurodevelopment in nonsyndromic craniosynostosis patients remains unexplored.
METHODS
The authors performed whole-exome sequencing for 404 case-parent trios with sporadic nonsyndromic craniosynostosis. Statistical analyses were performed to assess the burden of de novo mutations in cases compared to both expectation and 1789 healthy control trios. Individuals with and without each mutation class were analyzed, and the presence or absence of various types of neurodevelopmental delay were recorded alongside demographic information.
RESULTS
The authors identified a highly significant burden of damaging de novo mutations in mutation-intolerant [probability of loss of function intolerance (pLI) >0.9] genes in nonsyndromic craniosynostosis probands (p = 5.9 × 10-6). Children with these mutations had a two-fold higher incidence of neurodevelopmental delay (p = 0.001) and a more than 20-fold greater incidence of intellectual disability (p = 7.2 × 10-7), and were 3.6-fold more likely to have delays that persisted past 5 years of age (p = 4.4 × 10-4) in comparison with children with nonsyndromic craniosynostosis without these mutations. Transmitted loss of function mutations in high-pLI genes also conferred a 1.9-fold greater risk of neurodevelopmental delay (p = 4.5 ×10-4).
CONCLUSIONS
These findings implicate genetic lesions concurrently impacting neurodevelopment and cranial morphogenesis in the pathoetiology of nonsyndromic craniosynostosis and identify a strong genetic influence on neurodevelopmental outcomes in affected children. These findings may eventually prove useful in determining which children with nonsyndromic craniosynostosis are most likely to benefit from surgical intervention.
CLINICAL QUESTION/LEVEL OF EVIDENCE
Risk, III.
Topics: Child; Craniosynostoses; Humans; Incidence; Mutation; Skull; Exome Sequencing
PubMed: 35286293
DOI: 10.1097/PRS.0000000000008976