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Neurosurgical Focus: Video Apr 2021The multidirectional cranial distraction osteogenesis (MCDO) procedure, which uses an external distraction device, enables tailor-made distraction in an arbitrary...
The multidirectional cranial distraction osteogenesis (MCDO) procedure, which uses an external distraction device, enables tailor-made distraction in an arbitrary direction, eliminating the disadvantage of unidirectional distraction with an internal distraction device. Multiple-suture synostosis cases for syndromic craniosynostosis patients are better indicated for this procedure. Here the authors describe seven cases in which the MCDO procedure was used to treat syndromic craniosynostosis. In each case, the MCDO procedure and postoperative distraction, with reference to midsagittal vector analysis of normal morphology in Japanese children, resulted in morphological improvement. The video can be found here: https://vimeo.com/519006555.
PubMed: 36284845
DOI: 10.3171/2021.1.FOCVID20116 -
Archivos Argentinos de Pediatria Apr 2021The Saethre-Chotzen syndrome is a craniofacial malformation syndrome characterized by synostosis of coronal sutures and limb anomalies. The estimated prevalence of this...
The Saethre-Chotzen syndrome is a craniofacial malformation syndrome characterized by synostosis of coronal sutures and limb anomalies. The estimated prevalence of this syndrome is 1 in 25 000-50 000 live births. We present a case report of a neonate, without relevant family history, who presented craniofacial alterations at birth. Given the phenotypic features, a cranial computed tomography scan was performed, showing partial fusion of the coronal suture, evidencing the presence Síndrome de Saethre-Chotzen: a propósito de un caso Saethre-Chotzen syndrome: a case report of wormian bones in the metopic and right lambdoid location. With the clinical suspicion of craniofacial malformation syndrome, an analysis of the directed exome was requested confirming that the patient is a heterozygous carrier of the pathogenic variant c.415C>A, which induces a change of proline to threonine at position 139 of the TWIST1 gene, responsible for Saethre-Chotzen syndrome. The presence of wormian bones, a finding not described so far in the literature, extends the well-known phenotypic variability of this syndrome.
Topics: Acrocephalosyndactylia; Cranial Sutures; Heterozygote; Humans; Infant, Newborn; Nuclear Proteins; Twist-Related Protein 1
PubMed: 33749202
DOI: 10.5546/aap.2021.e129 -
World Journal of Clinical Cases Feb 2021Most cases of Apert syndrome (AS) are found after birth. Cases of AS diagnosed by ultrasound combined with magnetic resonance imaging (MRI) and whole exome sequencing...
BACKGROUND
Most cases of Apert syndrome (AS) are found after birth. Cases of AS diagnosed by ultrasound combined with magnetic resonance imaging (MRI) and whole exome sequencing (WES) during pregnancy are rare.
CASE SUMMARY
We present the case of a 34-year old female patient (gravida 2, para 1) whose fetus was diagnosed with AS during pregnancy. Fetal ultrasound performed at 30, 2/7 wk of pregnancy showed abnormalities. MRI and three-dimensional ultrasound performed at 31, 1/7 wk of pregnancy showed the possibility of AS. Chromosome examination and core family WES were conducted at 31, 5/7 wk of pregnancy. The results showed that in the fetus had a c.755C>G missense mutation in its nucleotide, and AS was confirmed.
CONCLUSION
This case highlights the importance of imaging examinations. Prenatal ultrasound combined with MRI can identify fetal morphological abnormalities accurately, which can be confirmed by WES.
PubMed: 33585639
DOI: 10.12998/wjcc.v9.i4.912 -
JPRAS Open Mar 2021Le Fort II advancement is considered for normalizing the facial appearance in Apert syndrome. When these procedures are performed during growth, overcorrection of...
BACKGROUND
Le Fort II advancement is considered for normalizing the facial appearance in Apert syndrome. When these procedures are performed during growth, overcorrection of midface advancement is required. We developed a system that can control the distance and vector of movement for the central midface to create more normal facial proportions. This case report shows Le Fort II distraction osteogenesis with this hybrid system for an Apert syndrome patient.
CASE
The patient was a girl with Apert syndrome with midfacial-nose hypoplasia and skeletal class III malocclusion. She was healthy without respiratory problems and had no learning disabilities. She underwent our Le Fort II distraction osteogenesis with the hybrid system at 10 years and 6 months of age. Her midface was elongated 22 mm at point Or forward and moved 5° downward to the Frankfort horizontal plane compared to the standard position of average Japanese adult women on the cephalogram. Examining the facial image, the midfacial depression was improved 4 years after the operation.
DISCUSSION
Overcorrection of midface advancement is required for patients to reduce the number of procedures during growth. The system that we developed could control the distance and vector of movement steadily when the central midface was overcorrected to try to create normal adult facial proportions.
PubMed: 33313372
DOI: 10.1016/j.jpra.2020.10.007 -
Stem Cell Research & Therapy Dec 2020During development, excessive osteogenic differentiation of mesenchymal progenitor cells (MPC) within the cranial sutures can lead to premature suture fusion or...
BACKGROUND
During development, excessive osteogenic differentiation of mesenchymal progenitor cells (MPC) within the cranial sutures can lead to premature suture fusion or craniosynostosis, leading to craniofacial and cognitive issues. Saethre-Chotzen syndrome (SCS) is a common form of craniosynostosis, caused by TWIST-1 gene mutations. Currently, the only treatment option for craniosynostosis involves multiple invasive cranial surgeries, which can lead to serious complications.
METHODS
The present study utilized Twist-1 haploinsufficient (Twist-1) mice as SCS mouse model to investigate the inhibition of Kdm6a and Kdm6b activity using the pharmacological inhibitor, GSK-J4, on calvarial cell osteogenic potential.
RESULTS
This study showed that the histone methyltransferase EZH2, an osteogenesis inhibitor, is downregulated in calvarial cells derived from Twist-1 mice, whereas the counter histone demethylases, Kdm6a and Kdm6b, known promoters of osteogenesis, were upregulated. In vitro studies confirmed that siRNA-mediated inhibition of Kdm6a and Kdm6b expression suppressed osteogenic differentiation of Twist-1 calvarial cells. Moreover, pharmacological targeting of Kdm6a and Kdm6b activity, with the inhibitor, GSK-J4, caused a dose-dependent suppression of osteogenic differentiation by Twist-1 calvarial cells in vitro and reduced mineralized bone formation in Twist-1 calvarial explant cultures. Chromatin immunoprecipitation and Western blot analyses found that GSK-J4 treatment elevated the levels of the Kdm6a and Kdm6b epigenetic target, the repressive mark of tri-methylated lysine 27 on histone 3, on osteogenic genes leading to repression of Runx2 and Alkaline Phosphatase expression. Pre-clinical in vivo studies showed that local administration of GSK-J4 to the calvaria of Twist-1 mice prevented premature suture fusion and kept the sutures open up to postnatal day 20.
CONCLUSION
The inhibition of Kdm6a and Kdm6b activity by GSK-J4 could be used as a potential non-invasive therapeutic strategy for preventing craniosynostosis in children with SCS. Pharmacological targeting of Kdm6a/b activity can alleviate craniosynostosis in Saethre-Chotzen syndrome. Aberrant osteogenesis by Twist-1 mutant cranial suture mesenchymal progenitor cells occurs via deregulation of epigenetic modifiers Ezh2 and Kdm6a/Kdm6b. Suppression of Kdm6a- and Kdm6b-mediated osteogenesis with GSK-J4 inhibitor can prevent prefusion of cranial sutures.
Topics: Acrocephalosyndactylia; Animals; Histone Demethylases; Jumonji Domain-Containing Histone Demethylases; Mice; Molecular Targeted Therapy; Nuclear Proteins; Osteogenesis; Twist-Related Protein 1
PubMed: 33298158
DOI: 10.1186/s13287-020-02051-5 -
AJNR. American Journal of Neuroradiology Jan 2021Cerebellar tonsillar herniation arises frequently in syndromic craniosynostosis and causes central and obstructive apneas in other diseases through spinal cord...
BACKGROUND AND PURPOSE
Cerebellar tonsillar herniation arises frequently in syndromic craniosynostosis and causes central and obstructive apneas in other diseases through spinal cord compression. The purposes of this study were the following: 1) to determine the prevalence of cervical spinal cord compression in syndromic craniosynostosis, and 2) to evaluate its connection with sleep-disordered breathing.
MATERIALS AND METHODS
This was a cross-sectional study including patients with syndromic craniosynostosis who underwent MR imaging and polysomnography. Measures encompassed the compression ratio at the level of the odontoid process and foramen magnum and the cervicomedullary angle. MR imaging studies of controls were included. Linear mixed models were developed to compare patients with syndromic craniosynostosis with controls and to evaluate the association between obstructive and central sleep apneas and MR imaging parameters.
RESULTS
One hundred twenty-two MR imaging scans and polysomnographies in 89 patients were paired; 131 MR imaging scans in controls were included. The mean age at polysomnography was 5.7 years (range, 0.02-18.9 years). The compression ratio at the level of the odontoid process was comparable with that in controls; the compression ratio at the level of the foramen magnum was significantly higher in patients with Crouzon syndrome (+27.1, < .001). The cervicomedullary angle was significantly smaller in Apert, Crouzon, and Saethre-Chotzen syndromes (-4.4°, = .01; -10.2°, < .001; -5.2°, = .049). The compression ratios at the level of the odontoid process and the foramen magnum, the cervicomedullary angle, and age were not associated with obstructive apneas (> .05). Only age was associated with central apneas (= .02).
CONCLUSIONS
The prevalence of cervical spinal cord compression in syndromic craniosynostosis is low and is not correlated to sleep disturbances. However, considering the high prevalence of obstructive sleep apnea in syndromic craniosynostosis and the low prevalence of compression and central sleep apnea in our study, we would, nevertheless, recommend a polysomnography in case of compression on MR imaging studies.
Topics: Adolescent; Child; Child, Preschool; Craniosynostoses; Cross-Sectional Studies; Female; Humans; Infant; Infant, Newborn; Magnetic Resonance Imaging; Male; Polysomnography; Prevalence; Sleep Apnea Syndromes; Spinal Cord Compression
PubMed: 33272949
DOI: 10.3174/ajnr.A6881 -
BMC Musculoskeletal Disorders Nov 2020Apert syndrome is characterised by the presence of craniosynostosis, midface retrusion and syndactyly of hands and feet, thus, synonymously referred to as... (Review)
Review
BACKGROUND
Apert syndrome is characterised by the presence of craniosynostosis, midface retrusion and syndactyly of hands and feet, thus, synonymously referred to as acrocephalosyndactyly type I. Considering these multidisciplinary issues, frequently requiring surgical interventions at an early age, deformities of the feet have often been neglected and seem to be underestimated in the management of Apert syndrome. Typical Apert foot features range from complete fusion of the toes and a central nail mass to syndactyly of the second to fifth toe with a medially deviated great toe; however, no clear treatment algorithms were presented so far. This article reviews the current existing literature regarding the treatment approach of foot deformities in Apert syndrome.
STATE-OF-THE-ART TOPIC REVIEW
Overall, the main focus in the literature seems to be on the surgical approach to syndactyly separation of the toes and the management of the great toe deformity (hallux varus). Although the functional benefit of syndactyly separation in the foot has yet to be determined, some authors perform syndactyly separation usually in a staged procedure. Realignment of the great toe and first ray can be performed by multiple means including but not limited to second ray deletion, resection of the proximal phalanx delta bone on one side, corrective open wedge osteotomy, osteotomy of the osseous fusion between metatarsals I and II, and metatarsal I lengthening using gradual osteodistraction. Tarsal fusions and other anatomical variants may be present and have to be corrected on an individual basis. Shoe fitting problems are frequently mentioned as indication for surgery while insole support may be helpful to alleviate abnormal plantar pressures.
CONCLUSION
There is a particular need for multicenter studies to better elaborate surgical indications and treatment plans for this rare entity. Plantar pressure measurements using pedobarography should be enforced in order to document the biomechanical foot development and abnormalities during growth, and to help with indication setting. Treatment options may include conservative means (i.e. insoles, orthopedic shoes) or surgery to improve biomechanics and normalize plantar pressures.
LEVEL OF EVIDENCE
Level V.
Topics: Acrocephalosyndactylia; Foot Deformities; Hand; Humans; Metatarsal Bones; Osteotomy
PubMed: 33248465
DOI: 10.1186/s12891-020-03812-2 -
Surgical Neurology International 2020Apert syndrome is one of the most severe craniofacial disorders. This study aims to describe the craniofacial surgeries and central nervous system malformations of a...
BACKGROUND
Apert syndrome is one of the most severe craniofacial disorders. This study aims to describe the craniofacial surgeries and central nervous system malformations of a cohort of children with Apert syndrome treated in the past 20 years and to compare these data with previously published data.
METHODS
Retrospective analysis of a series of patients with Apert syndrome treated between 1999 and 2019 in our hospital. Information was analyzed regarding craniofacial procedures, hydrocephalus and presence of shunts, Chiari malformation Type 1, and other brain malformations such as corpus callosum and septum pellucidum anomalies.
RESULTS
Thirty-seven patients were studied. Ventriculoperitoneal shunt prevalence was 24.3%, and 8.1% of patients required decompressive surgery for Chiari malformation. All of them needed at least one cranial vault remodeling procedure. The median age for this procedure was 8 months. In 69.7% of patients, the first cranial vault intervention was performed in the fronto-orbital region. In 36.4% of patients, a midface advancement had been performed at the time of this review, although this proportion was very dependent on the follow-up period and the age of the patients. The median age for the midface advancement procedure was 5.25 years. Anomalies of the corpus callosum and the septum pellucidum were reported in 43.2% and 59.5% of patients, respectively.
CONCLUSION
Apert syndrome is a type of syndromic craniosynostosis, and patients usually require one or more cranial and facial surgeries. In comparison with other syndromic craniosynostosis types, Apert syndrome less frequently requires a VP shunt or treatment for a Chiari malformation.
PubMed: 33194294
DOI: 10.25259/SNI_413_2020 -
Dermatology Practical & Conceptual Oct 2020The skin is often seen as a world apart, but not rarely do cutaneous manifestations reveal signs of systemic disease. (Review)
Review
BACKGROUND
The skin is often seen as a world apart, but not rarely do cutaneous manifestations reveal signs of systemic disease.
OBJECTIVES
The aim of this review is to include in one paper all the possible correlations between nephrological and dermatological manifestations of the same disease in pediatric patients while also keeping in mind that in apparent exclusively dermatological diseases there can be nephrological manifestations as part of the same disorder and vice versa.
METHODS
We searched on PubMed for a possible link between skin and kidney matching the following terms and correlated MeSH terms: dermatology, skin, kidney, renal disease, nephrology, pediatrics, child, childhood, vasculitis, and cancer. We selected only articles reporting a link between nephrology and dermatology in pediatrics, and they are all included in this comprehensive review.
RESULTS
Kawasaki disease, Henoch-Schönlein purpura, systemic lupus erythematosus, Dent disease, subcutaneous fat necrosis, Langerhans cell histiocytosis, renal cell carcinoma, non-Hodgkin lymphoma, tuberous sclerosis complex and syndromes with increased risk for Wilms tumor, Fabry disease, nail-patella syndrome, neurofibromatosis type 1, Beckwith-Wiedemann syndrome, Adams-Oliver syndrome 1, Apert syndrome, Fanconi pancytopenia syndrome, Pallister-Hall syndrome, and Fanconi pancytopenia syndrome are all conditions in which there can be both nephrological and dermatological manifestations in children.
CONCLUSIONS
We could not find any reports that focused attention on the link between nephrological and dermatological manifestations of the same disease in children. It is also important for clinicians to keep in mind that in what may appear to be an exclusively dermatological disease, there can be nephrological manifestations as part of the same disorder and vice versa.
PubMed: 33150036
DOI: 10.5826/dpc.1004a95 -
Pediatrics and Neonatology Jan 2021
PubMed: 33077402
DOI: 10.1016/j.pedneo.2020.09.009