Craniosynostosis

Craniosynostosis merupakan fusi prematur dan patologis, baik parsial atau lengkap dari satu atau lebih sutura kranial. Craniosynostosis tidak hanya terbatas pada deformitas cranium, namun juga menyebabkan berbagai masalah neurologis pada anak yang sedang tumbuh. Hipertensi intrakranial, malformasi hidrosefalus dan Chiari adalah masalah yang sering timbul berkaitan dengan craniosynostosis. Deformitas cranium dan masalah neurologis ini menyebabkan disfungsi neurologis dan kognitif

Craniosynostosis is a congenial malformation caused by premature fusion of one or more cranial sutures, leading to abnormal shape of the skull. Non-syndromic craniosynostoses can result in developmental disorders, including speech acquisition delay. The authors have carried out neurologopaedic research on a group of 124 children aged 3 to 59 months of life. In these cases, causes of speech disorders are very complex. Additional research concerning speech and language development in school age children with craniosynostoses is essential.

Introduction: Craniosynostosis, the premature fusion of cranial sutures, is usually divided into 2 major categories: syndromic and nonsyndromic. Mutations in the FGFR1, FGFR2, FGFR3, TWIST1, and EFNB1 genes cause the common craniosynostosis syndromes Muenke, Crouzon and Crouzon with acanthosis nigricans, Apert, Pfeiffer, Saethre-Chotzen, and Craniofrontonasal. Overlapping features among craniosynostosis syndromes, phenotypic heterogeneity even within the same syndrome, especially in the case of Muenke syndrome, and inadequate clinical evaluation can lead to misdiagnosis, which molecular testing can help clarify.

Introduction Chiari malformation (CM) is a frequent finding in multisutural and syndromic craniosynostosis, occurring in 70% of patients with Crouzon’s syndrome, 75% with oxycephaly, 50% with Pfeiffer’s syndrome and 100% with the Kleeblattschädel deformity. The pathogenesis of this condition and rationale for treatment are still controversial. Discussion Since its first description in 1972, several factors have been cited to play a role in inducing CM. In the light of recent publications, the roles of premature fusion of cranial vault and cranial base sutures, of congenital anomalies of the cerebellum and brain stem, of raised intracranial pressure, of venous hypertension and of hydrocephalus are reviewed. Evaluation and management of CM are also discussed. Conclusion Chiari malformation appears to be an acquired and progressive condition that develops in the first months of life, because of a disproportion between hindbrain growth and an abnormally small posterior fossa, a consequence of the premature fusion of lambdoid and cranial base sutures. Venous hypertension caused by stenosis of the jugular foramen can also be present in these patients, resulting in intracranial hypertension and/or hydrocephalus. Careful MRI evaluation is recommended for the forms of craniosynostosis at a high risk of developing hindbrain herniation. The selection of posterior cranial vault expansion as the first surgical procedure is advocated. In selected cases, treatment of the posterior cranial deformity by occipital vault remodelling and treatment of the Chiari-like deformity by suboccipital decompression can be carried out using the same surgical procedure.

Speech therapy should be an integral part of the support for children with craniosynostosis. Knowledge and research pathological deformation of the head in children are presented in this article. Needs should not only focus on the improvement of cranial distortion that results from premature closure of the sutures between the bone of the skull, but also focus on improving the quality of life of patients and their families. Speech and language therapy for children with deformities of the skull and face, requires in-depth knowledge of a speech therapist and therapeutic treatment should be started on the exact type of exercise to adapt to the needs of speech therapy. Wstęp Poszukując w historii gatunku ludzkiego momentu, kiedy człowiek pierwotny po raz pierwszy posługiwał się mową, należy odnieść się do prehistorycznych cza-sów, do skamieniałych czaszek lub do ich fragmentów. Na podstawie ich struktury można wnioskować, czy budowa głowy człowieka pierwotnego spełniała anatomicz-ne warunki niezbędne do posługiwania się mową. W 1971 roku Philip Lieberman i Edmund S. Crelin sformułowali hipotezę, według której człowiek może w sposób efektywny posługiwać się mową pod warunkiem, że podstawa jego czaszki ma odpowiednią budowę. Analizując czaszki neandertalczyka, badacze ci ocenili, że zagięcie w dole podstawy w tylnej okolicy jamy czaszki świadczy o tym, że mógł się on posługiwać mową 1. Zagięcie tylnej części podstawy czaszki umożliwiało bowiem stworzenie odpowiedniej przestrzeni w obrębie struktur nosogardła i jamy ustnej, tym samym mogło przyczyniać się do powstania odpowiedniego połączenia ich ze 1 P. Lieberman, E.S. Crelin: On the speech of Neanderthal. "Linguistic Inquiry" 1971, No. 2, s. 203-222.

Background: The developmental basis of craniofacial morphology hinges on interactions of numerous signalling systems. Extensive craniofacial variation in the polymorphic Arctic charr, a member of the salmonid family, from Lake Thingvallavatn (Iceland), offers opportunities to find and study such signalling pathways and their key regulators, thereby shedding light on the developmental pathways, and the genetics of trophic divergence. Results: To identify genes involved in the craniofacial differences between benthic and limnetic Arctic charr, we used transcriptome data from different morphs, spanning early development, together with data on craniofacial expression patterns and skeletogenesis in model vertebrate species. Out of 20 genes identified, 7 showed lower gene expression in benthic than in limnetic charr morphs. We had previously identified a conserved gene network involved in extracel-lular matrix (ECM) organization and skeletogenesis, showing higher expression in developing craniofacial elements of benthic than in limnetic Arctic charr morphs. The present study adds a second set of genes constituting an expanded gene network with strong, benthic–limnetic differential expression. To identify putative upstream regulators, we performed knowledge-based motif enrichment analyses on the regulatory sequences of the identified genes which yielded potential binding sites for a set of known transcription factors (TFs). Of the 8 TFs that we examined using qPCR, two (Ahr2b and Ap2) were found to be differentially expressed between benthic and limnetic charr. Expression analysis of several known AhR targets indicated higher activity of the AhR pathway during craniofacial development in benthic charr morphotypes. Conclusion: These results suggest a key role of the aryl hydrocarbon receptor (AhR) pathway in the observed crani-ofacial differences between distinct charr morphotypes.

Compound heterozygous mutations in the IFT140 gene cause Opitz trigonocephaly C syndrome in a patient with typical features of a ciliopathy. Clin Genet 2017. We report on an infant with Opitz trigonocephaly C syndrome (OTCS), who also had manifestations of ciliopathy, including short ribs (non-asphyxiating), trident acetabular roofs, postaxial polydactyly cone-shaped epiphyses, and dysplasia of the renal, hepatic and pancreatic tissues. To investigate the molecular cause, we used an exome sequencing strategy followed by Sanger sequencing. Two rare variants, both predicted to result in loss of functional protein, were identified in the IFT140 gene; a substitution at the splice donor site of exon 24 (c.723 + 1 G > T) and a 17 bp deletion, impacting the first coding exon (c.-11_6del). The variants were confirmed as being biallelic using Sanger sequencing, showing that the splice variant was inherited from the propositus mother and the deletion from the father. To date, Mainzer–Saldino syndrome, Jeune syndrome, and a form of nonsyndromic retinal dystrophy, have been identified as ciliopathies caused by IFT140 mutations. We provide the first description of an OTCS phenotype that appears to result from IFT140 mutations. The presentation of this patient is consistent with previous reports showing that OTCS already exhibited skeleletal and nonskeletal features of a ciliopathy.

Introduction Chiari malformation (CM) is a frequent finding in multisutural and syndromic craniosynostosis, occurring in 70% of patients with Crouzon’s syndrome, 75% with oxycephaly, 50% with Pfeiffer’s syndrome and 100% with the Kleeblattschädel deformity. The pathogenesis of this condition and rationale for treatment are still controversial. Discussion Since its first description in 1972, several factors have been cited to play a role in inducing CM. In the light of recent publications, the roles of premature fusion of cranial vault and cranial base sutures, of congenital anomalies of the cerebellum and brain stem, of raised intracranial pressure, of venous hypertension and of hydrocephalus are reviewed. Evaluation and management of CM are also discussed. Conclusion Chiari malformation appears to be an acquired and progressive condition that develops in the first months of life, because of a disproportion between hindbrain growth and an abnormally small posterior fossa, a consequence of the premature fusion of lambdoid and cranial base sutures. Venous hypertension caused by stenosis of the jugular foramen can also be present in these patients, resulting in intracranial hypertension and/or hydrocephalus. Careful MRI evaluation is recommended for the forms of craniosynostosis at a high risk of developing hindbrain herniation. The selection of posterior cranial vault expansion as the first surgical procedure is advocated. In selected cases, treatment of the posterior cranial deformity by occipital vault remodelling and treatment of the Chiari-like deformity by suboccipital decompression can be carried out using the same surgical procedure.

Crouzon syndrome is a rare genetic disorder with autosomal dominant inheritance with the prevalence of 1 in 25,000 live births, and it constitutes 4.8% of all craniosynostosis. Maxillary hypoplasia, craniosynostosis, shallow orbits, ocular proptosis and hypertelorism are the characteristic features of Crouzon syndrome. This report describes a patient with crouzon syndrome showing characteristic dentofacial deformities, along with review of literature.

Objective: To characterize the craniofacial phenotype of a mouse model for Crouzon syndrome by a quantitative analysis of skull morphology in mutant and wild-type mice and to compare the findings with skull features observed in humans with Crouzon syndrome. Methods: MicroCT scans and skeletal preparations were obtained on previously described Fgfr2C342Y/+ Crouzon mutant mice and wild-type mice at 6 weeks of age. Three-dimensional coordinate data from biologically relevant landmarks on the skulls were collected. Euclidean Distance Matrix Analysis was used to quantify and compare skull shapes using these landmark data. Results: Obliteration of bilateral coronal sutures was observed in 80% of skulls, and complete synostosis of the sagittal suture was observed in 70%. In contrast, fewer than 40% of lambdoid sutures were found to be fully fused. In each of the 10 Fgfr2C342Y/+ mutant mice analyzed, the presphenoid-basisphenoid synchondrosis was fused. Skull height and width were increased...

Deformational plagiocephaly, unilateral coronal craniosynostosis, and lambdoid craniosynostosis all cause oblique deformities of the skull. They are separate entities with different etiologies resulting in clear differences of physical examination, radiologic findings, and clinical course. Treatment for each condition is markedly different. Surgical intervention is recommended for unilateral coronal and lambdoid craniosynostosis using different techniques. Deformational plagiocephaly, on the other hand, is often satisfactorily managed with conservative treatment. We present 4 clinical reports on patients in whom unilateral coronal craniosynostosis and lambdoid craniosynostosis were originally misdiagnosed as occipital deformational plagiocephaly and highlight individual structural distinctions.

Craniofrontonasal syndrome is mainly characterized by frontonasal dysplasia, telorbitism, a broad nasal root, and frequently a bifid nose and coronal craniosynostosis. Craniofrontonasal syndrome is an X-linked disorder with an unusual pattern of inheritance because heterozygous females are more severely affected than hemizygous males. The craniofrontonasal syndrome-causing gene is EFNB1, localized in the border region of chromosome Xq12 and Xq13.1, encoding for protein ephrin-B1. Here we aim to investigate the underlying genetic defect of a young girl with craniofrontonasal syndrome. The patient underwent surgical correction of her craniofacial deformities. Genetic analysis was carried out by polymerase chain reaction. Products of exon 2 of the EFNB1 gene were sequenced as well as digested with BpmI enzyme. A novel de novo missense mutation 373G>A was identified within the EFNB1 gene, leading to the replacement of glutamic acid at amino acid position 125 with lysine. The replacement of Glu125 with Lys, which lies within the G-H loop, part of the dimerization ligand-receptor interface, is expected to disrupt the interaction between the Eph receptor and ephrin B1 ligand, thus leading to craniofrontonasal syndrome.

La transformación morfológica extrínseca del neurocráneo se produce no por la retracción pasiva de los tejidos cefálicos sino por su expansión compensatoria. Durante este proceso, el cerebro y la bóveda craneal se expanden hacia las zonas no oprimidas. Este capítulo examinaalgunas nociones básicas de la expansión neuro- y craneológica humanadurante el crecimiento infantil natural. Igualmente recurrimos a la información anatómica y fisiopatológica para explicar luego las alteraciones operantes en la dinámica del creciemiento cefálico durante el proceso de compression externa. Especialmente la embriología craneana y lafisiología del desarrollo postnatal proporcionan valiosos puntos de partida para explorar y discutir las limitaciones naturales en los cambios inducidos ala forma de la bóveda craneal y sus efectos secundarios en la base y en la cara. Llegamos a confirmar que el modelado cefálico solo es posible durante los primeros años de vida y que los cambios en la formación del basi-y esplacnocráneovan en función del momento postnatal, del grado, la duración y de las técnicas del modelado. Su implementación cultural también puede tener implicaciones estéticas para el portador, como son la asimetríacefálicaconcomitante a la compression en cuna y una serie de riesgos para la saluden formade hemorragias, hipertensiónintracraneana, infecciones locales o la necrosis del tejido comprimido.

INTRODUCTION: Craniosynostosis is the simple early closure of one or more cranial sutures that causes abnormal growth of the skull and that can lead to abnormal growth of the brain. The treatment of craniosynostosis is surgical and eliminates growth restriction caused by the fused suture. Neurodevelopmental assessments in these patients have generated inconsistent results, with some authors reporting normal scores and other data showing psychomotor and cognitive delay.
OBJECTIVE: To determine if Battelle Developmental Inventory detects a delay in the acquisition of neuropsychological processes in patients afflicted with craniosynostosis and evaluate if surgical manipulation improvestheir neuropsychological development.
METHODS: We evaluated 8 children diagnosed with craniosynostosis and compared with 8 normal kids between 1 and 12 months old, by means of the Battelle Developmental Inventory before surgery, and to 5 patients reevaluated3 months after surgery to test their neuropsychological improvement.