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International Journal of Pediatric... Oct 2021Craniosynostosis is a bony dysmorphism of the calvarium due to premature suture fusion and is classified as syndromic (part of congenital syndrome) or nonsyndromic... (Review)
Review
BACKGROUND
Craniosynostosis is a bony dysmorphism of the calvarium due to premature suture fusion and is classified as syndromic (part of congenital syndrome) or nonsyndromic (isolated). Deformational plagiocephaly (DP) is due to external positional forces on the skull after birth. This review aims to investigate the various quality of life (QoL) metrics across syndromic, nonsyndromic and DP patients.
METHODS
Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature search was done through EMBASE, MEDLINE, PubMed and Web of Science. After two stages of screening by two authors, seventeen articles met inclusion criteria; 11 on syndromic, 4 nonsyndromic, and 2 DP.
RESULTS
The literature suggests syndromic patients have more severe consequences on QoL, especially on psychological well-being, social functioning, and obstructive sleep apnea (OSA), leading to behavioral difficulties. Nonsyndromic patients show a less clear trend across QoL measures, but a majority stated QoL is comparable to the general population. DP patients noted motor development and QoL improvement as well as improved subjective aesthetic outcomes after orthotic helmet molding therapy (HMT).
CONCLUSIONS
While a majority of literature classifies QoL in syndromic craniosynostosis alone, this review highlights the importance of these factors in nonsyndromic craniosynostosis and plagiocephaly patients. Psychological well-being, social functioning, and secondary health impacts such as OSA are important to consider in comprehensive craniofacial care in all calvaria deformities.
Topics: Craniosynostoses; Humans; Infant; Plagiocephaly; Plagiocephaly, Nonsynostotic; Quality of Life; Skull
PubMed: 34380097
DOI: 10.1016/j.ijporl.2021.110873 -
Insights and future directions of potential genetic therapy for Apert syndrome: A systematic review.Gene Therapy Nov 2021Apert syndrome is a genetic disorder characterised by craniosynostosis and structural discrepancy of the craniofacial region as well as the hands and feet. This... (Review)
Review
Apert syndrome is a genetic disorder characterised by craniosynostosis and structural discrepancy of the craniofacial region as well as the hands and feet. This condition is closely linked with fibroblast growth factor receptor-2 (FGFR2) gene mutations. Gene therapies are progressively being tested in advanced clinical trials, leading to a rise of its potential clinical indications. In recent years, research has made great progress in the gene therapy of craniosynostosis syndromes and several studies have investigated its influences in preventing/diminishing the complications of Apert syndrome. This article reviewed and exhibited different techniques of gene therapy and their influences in Apert syndrome progression. A systematic search was executed using electronic bibliographic databases including PubMed, EMBASE, ScienceDirect, SciFinder and Web of Science for all studies of gene therapy for Apert syndrome. The primary outcomes measurements vary from protein to gene expressions. According to the findings of included studies, we conclude that the gene therapy using FGF in Apert syndrome was critical in the regulation of suture fusion and patency, occurred via alterations in cellular proliferation. The superior outcome could be brought by biological therapies targeting the FGF/FGFR signalling. More studies in molecular genetics in Apert syndrome are recommended. This study reviews the current literature and provides insights to future possibilities of genetic therapy as intervention in Apert syndrome.
Topics: Acrocephalosyndactylia; Cell Proliferation; Genetic Therapy; Humans; Mutation; Signal Transduction
PubMed: 33619359
DOI: 10.1038/s41434-021-00238-w -
Journal of Pediatric Orthopedics. Part B Nov 2021Congenital radioulnar synostosis (CRUS) is one of the most common congenital disorders affecting the elbow and forearm, with the forearm being fixed in a range of...
Congenital radioulnar synostosis (CRUS) is one of the most common congenital disorders affecting the elbow and forearm, with the forearm being fixed in a range of positions usually varying from neutral rotation to severe pronation. The aim of this study, apart from a systematic review of all surgical procedures described for CRUS, is to derive any correlation between various influencing factors, outcomes and complications. This review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses format by an electronic literature search of Ovid, MEDLINE and the Cochrane Library databases. Grading was according to the Newcastle-Ottawa scale and the Modified Coleman Methodology Score. Demographic data, surgical procedures, outcomes and complications were analyzed. Outcome data were pooled to establish means and ranges across all studies. Spearman correlations were performed. A total of 23 articles, showing a poor overall study quality (all Level of Evidence IV), met the inclusion criteria. A total of 374 forearms with a mean age of 6.7 years (2.0-18.8) were analyzed. Derotational surgeries were more commonly performed (91%) than motion-preserving surgeries (9%). The mean deformity improved from 64.8° pronation (-75° to 110°) to a mean of 2.8° pronation (-50° to 80°). In total, 17.9% of patients presented with complications. A significant correlation was noted between age and major complications, proximal osteotomies and complications, and postoperative loss of reduction and double level osteotomies as the primary treatment modality. Most of the complications occurred above the threshold of 65-70° of correction and in children 7 years and above. Surgery is essential to improve the quality of life of children with CRUS. However, each type of surgery is associated with complications, along with the respective hardware being used in rotation osteotomies. Caution is, nevertheless, warranted in interpreting these results in view of the inherent limitations of the included studies.
Topics: Child; Data Analysis; Humans; Quality of Life; Radius; Synostosis; Treatment Outcome; Ulna
PubMed: 33315801
DOI: 10.1097/BPB.0000000000000841 -
The Journal of Craniofacial SurgeryCraniosynostosis can be associated with raised intracranial pressure (ICP), which can pose deleterious effects on the brain and vision if untreated. Estimating ICP in...
OBJECTIVE
Craniosynostosis can be associated with raised intracranial pressure (ICP), which can pose deleterious effects on the brain and vision if untreated. Estimating ICP in children is challenging, whilst gold standard direct intracranial measurement of ICP is invasive and carries risk. This systematic review aims to evaluate the role of optical coherence tomography (OCT), a noninvasive imaging technique, for detecting raised ICP in children with craniosynostosis.
METHODS
The authors conducted a systematic review of the literature published from inception until 19 August, 2019 in the Cochrane Central Register of Controlled Trials, PubMed, MEDLINE, and EMBASE. Eligible studies evaluated the role of OCT in detecting raised ICP in children aged 0 to 16 years with craniosynostosis. Main outcome measures were sensitivity and specificity of OCT parameters for raised ICP. Quality assessment was performed using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-sectional Studies.
RESULTS
Out of 318 records identified, data meeting the inclusion criteria were obtained from 3 studies. The quality of 2 studies was poor whilst 1 was fair. Optical coherence tomography demonstrated higher sensitivity and specificity for detecting raised ICP compared to fundus examination, clinical history, radiological testing, and visual field testing.
CONCLUSIONS
This systematic review demonstrated a lack of quality evidence for OCT as a screening tool for children with craniosynostosis. Further research is required to clarify the strength of OCT in this role and to determine which OCT parameters are most appropriate.
Topics: Child; Craniosynostoses; Cross-Sectional Studies; Humans; Intracranial Hypertension; Intracranial Pressure; Tomography, Optical Coherence
PubMed: 33185414
DOI: 10.1097/SCS.0000000000006771 -
Paediatric Anaesthesia Feb 2021This article describes the methodology used for the Pediatric Craniofacial Collaborative Group (PCCG) Consensus Conference.
OBJECTIVE
This article describes the methodology used for the Pediatric Craniofacial Collaborative Group (PCCG) Consensus Conference.
DESIGN
This is a novel Consensus Conference of national experts in Pediatric Craniofacial Surgery and Anesthesia, who will follow standards set by the Institute of Medicine and using the Research and Development/University of California, Los Angeles appropriateness method, modeled after the Pediatric Critical Care Transfusion and Anemia Expertise Initiative. Topics related to pediatric craniofacial anesthesia for open cranial vault surgery were divided into twelve subgroups with a systematic review of the literature.
SETTING
A group of 20 content experts met virtually between 2019 and 2020 and will collaborate in their selected topics related to perioperative management for pediatric open cranial vault surgery for craniosynostosis. These groups will also identify where future research is needed.
CONCLUSIONS
Experts in pediatric craniofacial surgery and anesthesiology are developing recommendations on behalf of the Pediatric Craniofacial Collaborative Group for perioperative management of patients undergoing open cranial vault surgery for craniosynostosis and identifying future research priorities.
Topics: Anemia; Blood Transfusion; Child; Craniosynostoses; Critical Care; Humans; Infant; Skull
PubMed: 33174262
DOI: 10.1111/pan.14066 -
Child's Nervous System : ChNS :... Feb 2021Pfeiffer syndrome (PS) is a rare autosomal dominant craniofacial disorder characterized by primary craniosynostosis, midface hypoplasia, and extremities' abnormalities... (Review)
Review
Pfeiffer syndrome (PS) is a rare autosomal dominant craniofacial disorder characterized by primary craniosynostosis, midface hypoplasia, and extremities' abnormalities including syndactyly. The purpose of this article was to review the current knowledge regarding how PS affects the nervous system. Methodologically, we conducted a systematic review of the existing literature concerning involvement of the nervous system in PS. Multiple-suture synostosis is common, and it is the premature fusion and abnormal growth of the facial skeleton's bones that cause the characteristic facial features of these patients. Brain abnormalities in PS can be primary or secondary. Primary anomalies are specific developmental brain defects including disorders of the white matter. Secondary anomalies are the result of skull deformity and include intracranial hypertension, hydrocephalus, and Chiari type I malformation. Spinal anomalies in PS patients include fusion of vertebrae, "butterfly" vertebra, and sacrococcygeal extension. Different features have been observed in different types of this syndrome. Cloverleaf skull deformity characterizes PS type II. The main neurological abnormalities are mental retardation, learning difficulties, and seizures. The tricky neurological examination in severely affected patients makes difficult the early diagnosis of neurological and neurosurgical complications. Prenatal diagnosis of PS is possible either molecularly or by sonography, and the differential diagnosis includes other craniosynostosis syndromes. Knowing how PS affects the nervous system is important, not only for understanding its pathogenesis and determining its prognosis but also for the guidance of decision-making in the various critical steps of its management. The latter necessitates an experienced multidisciplinary team.
Topics: Acrocephalosyndactylia; Brain; Craniosynostoses; Facial Bones; Humans; Hydrocephalus
PubMed: 33083874
DOI: 10.1007/s00381-020-04934-7 -
American Journal of Medical Genetics.... Nov 2020Oculo-auriculo-vertebral spectrum (hemifacial microsomia/OAVS, OMIM #164210) is a heterogenous and congenital condition caused by a morphogenesis defect of the first and...
Oculo-auriculo-vertebral spectrum (hemifacial microsomia/OAVS, OMIM #164210) is a heterogenous and congenital condition caused by a morphogenesis defect of the first and second pharyngeal arches. Etiology includes unknown genetic, environmental factors and chromosomal alterations, which 22q11.2 region is the most frequently reported. Several candidate genes for OAVS have been proposed; however, none has been confirmed as causative of the phenotype. This review aims to sum up all clinical and molecular findings in 22q region of individuals diagnosed with OAVS and to investigate genes that may be involved in the development of the spectrum. A search was performed in PubMed using all entry terms to OAVS and Chromosome 22q11. After screening, 11 papers were eligible for review. Deletions and duplications in the q11.2 region were the most frequent (18/22) alterations reported and a total of 68 genes were described. Our systematic review reinforces the hypothesis that 22q11 region is a candidate locus for OAVS as well as CLTCL1, GSC2, HIRA, MAPK1, TBX1, and YPEL1 as potential candidates genes for genotype-phenotype correlation. Complementary studies regarding genes interaction involved in the 22q11 region are still necessary in the search for a genotype-phenotype association, since the diagnosis of OAVS is a constant medical challenge.
Topics: Adolescent; Child; Child, Preschool; Chromosome Aberrations; Chromosomes, Human, Pair 22; Female; Gene Deletion; Gene Duplication; Genetic Association Studies; Genetic Predisposition to Disease; Goldenhar Syndrome; Humans; Infant; Male; Phenotype; Polymorphism, Single Nucleotide
PubMed: 32893956
DOI: 10.1002/ajmg.a.61841 -
The Journal of Craniofacial Surgery Sep 2020The fair comparison of treatment interventions for craniosynostosis across different studies is expected to be impaired by incomplete reporting and the use of...
CONTEXT
The fair comparison of treatment interventions for craniosynostosis across different studies is expected to be impaired by incomplete reporting and the use of inconsistent outcomes.
OBJECTIVE
This review assessed the outcomes currently reported in studies of craniosynostosis, and whether these outcomes are formally defined and prespecified in the study methods.
DATA SOURCES, SEARCH TERMS, AND STUDY SELECTION
Studies were sourced via an electronic, multi-database literature search for "craniosynostosis." All primary, interventional research studies published from 2011 to 2015 were reviewed.
DATA EXTRACTION
Two independent researchers assessed each study for inclusion and performed the data extraction. For each study, data were extracted on the individual outcomes reported, and whether these outcomes were defined and prespecified in the methods.
DATA SYNTHESIS AND RESULTS
Of 1027 studies screened, 240 were included and proceeded to data extraction. These studies included 18,365 patients.2192 separate outcomes were reported. Of these, 851 outcomes (38.8%) were clearly defined, 1394 (63.6%) were prespecified in the study methods."Clinical and functional" was the most commonly reported outcome theme (900 outcomes, 41.1%), and "patient-reported" outcomes the least (7 outcomes, 0.3%)."Duration of surgery" was the most commonly reported single outcome (reported 80 times). "Cranial index" was the most variably defined outcome (18 different definitions used).
CONCLUSION
The outcomes reported following treatment interventions for craniosynostosis are incompletely and variably defined. Improving definitions for these outcomes may aid comparison of different management strategies and improve craniosynostosis care. Suboptimal prespecification of these outcomes in the study methods implied that outcome reporting bias cannot be excluded.
Topics: Craniosynostoses; Humans; Outcome Assessment, Health Care
PubMed: 32740313
DOI: 10.1097/SCS.0000000000006680 -
International Journal of Pediatric... Jul 2020Treacher Collins syndrome (TCS) is a severe congenital mandibulofacial dysostosis that occurs one in every 50,000 births. The main clinical treatment of this rare...
OBJECTIVES
Treacher Collins syndrome (TCS) is a severe congenital mandibulofacial dysostosis that occurs one in every 50,000 births. The main clinical treatment of this rare disorder is reconstruction surgery. However, the high invasion, low security and long period of surgical intervention make it essential to explore prevention methods to decrease morbidity. The authors' aim is to summarize the prevention methods based on known mechanisms of TCS.
METHODS
A systematic review was conducted through an electronic search of PubMed, EMBASE and Web of Science databases through November 2019 using the following items: 'Treacher Collins syndrome OR TCS OR Franceschetti-Zwahlein-Klein syndrome OR Berry syndrome', 'gene therapy OR prevention'. Four causative gene names were also used. Articles which published in English language and explored the prevention methods for TCS were included and data concerning animal model, intervention, phenotype, conclusion were gathered.
RESULTS
Sixty-five studies were reviewed in total, and seven articles were included in this systematic review. Four articles used prevention methods related to the inhibition of p53, and three related to preclusion of oxidative stress-induced DNA damage.
CONCLUSIONS
This article provides a comprehensive review of the prevention methods for craniofacial abnormalities characteristic of TCS based on known pathogenesis in the current literatures. The craniofacial phenotype could be rescued through several treatment methods experimentally such as p53 inhibition and antioxidant administration.
Topics: Animals; Antioxidants; DNA Damage; Humans; Mandibulofacial Dysostosis; Oxidative Stress; Phenotype; Tumor Suppressor Protein p53
PubMed: 32361149
DOI: 10.1016/j.ijporl.2020.110062 -
International Journal of Oral and... Sep 2020Ocular anomalies may occur in craniofacial microsomia (CFM). The aim of this systematic review was to review the literature on ocular anomalies and their incidence, in...
Ocular anomalies may occur in craniofacial microsomia (CFM). The aim of this systematic review was to review the literature on ocular anomalies and their incidence, in order to estimate the need for ophthalmological screening in CFM patients. Online databases were searched, and data on the number of patients, type and incidence of ocular anomalies, and visual acuity were extracted. Four subgroups of ocular and adnexal anomalies were identified, to provide an overview of the different anomalies. Twenty-five papers analysing 1419 patients in total were included. Ocular anomalies were documented in 6.7-100% of patients. The most reported type I ocular anomalies were eyelid coloboma, lipodermoids, and orbital dystopia. The most reported type II ocular anomalies were epibulbar dermoid, microphthalmia, and anophthalmia. Ptosis and strabismus were the most reported type III anomalies, and irregular astigmatism was the most reported type IV ocular anomaly. Visual impairment in general was reported in 8-71.4% of patients, with severe visual impairment in 11.1-71.4% and amblyopia in 16.3%. This study provides a detailed overview of ocular anomalies in CFM and their prevalence. Furthermore, we propose a new classification to organize ocular anomalies into four clinically relevant subtypes. Finally, the high prevalence of ocular anomalies and visual impairment in this study suggests that CFM patients should undergo ophthalmological screening at least once during the sensitive period.
Topics: Coloboma; Face; Goldenhar Syndrome; Humans; Prevalence; Strabismus
PubMed: 32217034
DOI: 10.1016/j.ijom.2020.03.003