Cerebral cortex maldevelopment in syndromic craniosynostosis.

Aim: To assess the relationship of surface area of the cerebral cortex to intracranial volume (ICV) in syndromic craniosynostosis.

Method: Records of 140 patients (64 males, 76 females; mean age 8y 6mo [SD 5y 6mo], range 1y 2mo-24y 2mo) with syndromic craniosynostosis were reviewed to include clinical and imaging data. Two hundred and three total magnetic resonance imaging (MRI) scans were evaluated in this study (148 patients with fibroblast growth factor receptor [FGFR], 19 patients with TWIST1, and 36 controls).

European Reference Networks: challenges and opportunities.

European Reference Networks (ERNs) were founded on the principle that many rare disease (RD) issues are pan-European and any single Member State cannot solve them alone. In 2021, ERNs are already in the deployment stage; however, their day-to-day functioning and realization of their potential are still severely hampered by many challenges, including issues in governance and regulation, lack of legal status, insufficient and unsustainable funding, lack of ERN integration into national systems, endangered collaboration with UK RD experts due to Brexit, insufficient exploitation of ERN potential in RD research, underappreciation of highly qualified human resources, problems with the involvement of patient representatives, and still unclear place of ERNs in the overall European RD and digital ecosystem. Bold and innovative solutions that must be taken to solve these challenges inevitably involve pan-European collaboration across several sectors and among multistakeholder RD communities and in many cases crucially rely on the constructive dialogue and coherent, united decisions of national and European authorities that are based on common EU values.

Saethre-Chotzen syndrome: long-term outcome of a syndrome-specific management protocol.

Aim: To assess the long-term outcomes of our management protocol for Saethre-Chotzen syndrome, which includes one-stage fronto-orbital advancement.

Method: All patients born with Saethre-Chotzen syndrome between January 1992 and March 2017 were included. Evaluated parameters included occipital frontal head circumference (OFC), fundoscopy, neuroimaging (ventricular size, tonsillar position, and the presence of collaterals/an abnormal transverse sinus), polysomnography, and ophthalmological outcomes.

Surgical Correction of Craniofacial Microsomia: Evaluation of Interventions in 565 Patients at Three Major Craniofacial Units.

Background: Craniofacial microsomia is characterized by an asymmetric hypoplasia of derivatives of the first and second pharyngeal arch, leading to a variety of phenotypic presentations. Studies on surgical correction of patients with craniofacial microsomia have small cohorts, leaving controversial opinions on the optimal treatment modality, the indication for surgery, and the optimal timing of surgery. The purpose of this study was to evaluate the types of, timing of, and total number of surgical corrections performed and the number of surgical procedures in correlation to the severity of the phenotype.

Minimally Invasive, Spring-Assisted Correction of Sagittal Suture Synostosis: Technique, Outcome, and Complications in 83 Cases.

Background: This series describes the results of minimally invasive strip craniotomy with additional spring distraction.

Methods: Included are the first 83 consecutive patients who underwent this procedure (January 1, 2010, to January 1, 2014). Outcome parameters were collected prospectively and included surgical parameters and complications, the occurrence of papilledema, skull growth, cephalic index, and photographic scores.

The effect of early fusion of the spheno-occipital synchondrosis on midface hypoplasia and obstructive sleep apnea in patients with Crouzon syndrome.

Introduction: The investigators hypothesized that patients with Crouzon syndrome and premature fusion of the spheno-occipital synchondrosis (SOS) more often have, or have more severe midface hypoplasia and obstructive sleep apnea (OSA).

Methods: A prospective cohort study was performed among patients with Crouzon syndrome to analyze SOS closure, midface hypoplasia represented by the sella-nasion angle (SNA) and OSA.

Results: Forty patients were included in whom the OSA-prevalence was 65%.

Diagnostic value of exome and whole genome sequencing in craniosynostosis.

Background: Craniosynostosis, the premature fusion of one or more cranial sutures, occurs in ∼1 in 2250 births, either in isolation or as part of a syndrome. Mutations in at least 57 genes have been associated with craniosynostosis, but only a minority of these are included in routine laboratory genetic testing.

Methods: We used exome or whole genome sequencing to seek a genetic cause in a cohort of 40 subjects with craniosynostosis, selected by clinical or molecular geneticists as being high-priority cases, and in whom prior clinically driven genetic testing had been negative.

Non-surgical and surgical interventions for airway obstruction in children with Robin Sequence.

There is widespread lack of consensus regarding treatment of airway obstruction in children with Robin Sequence. This study aimed to systematically summarize outcomes of non-surgical and surgical options to treat airway obstruction in children with Robin Sequence. The authors searched the Medline, EMBASE and CENTRAL databases.

Volume measurements on three-dimensional photogrammetry after extended strip versus total cranial remodeling for sagittal synostosis: A comparative cohort study.

Background: Surgery for sagittal synostosis aims at correction of skull shape and restoration of growth potential. Small cranial volume is associated with raised intracranial pressure (ICP). Although many techniques have been described, information on postoperative volume related to early and late remodeling is lacking.

Quality of life in children with Robin Sequence.

Introduction: Parents may play an important role during the management of children with Robin Sequence (RS). However, so far only one study has been done on both parent-reported health-related quality of life (HRQoL) and obstructive sleep apnea (OSA) symptoms in children with RS.

Methods: Overall, 63 children with RS, aged 1 and 18, were included in this cross-sectional study.

Identification of Intragenic Exon Deletions and Duplication of TCF12 by Whole Genome or Targeted Sequencing as a Cause of TCF12-Related Craniosynostosis.

TCF12-related craniosynostosis can be caused by small heterozygous loss-of-function mutations in TCF12. Large intragenic rearrangements, however, have not been described yet. Here, we present the identification of four large rearrangements in TCF12 causing TCF12-related craniosynostosis.

Upper airway endoscopy to optimize obstructive sleep apnea treatment in Apert and Crouzon syndromes.

Introduction: Obstructive sleep apnea (OSA) is highly prevalent in children with Apert and Crouzon syndromes. Although often related to midface hypoplasia, it is a multi-level problem for which routine midface advancement might be a suboptimal treatment choice. We therefore wished to: 1.

Effect of Presurgical Positioning on Skull Shape in Sagittal Suture Synostosis.

Purpose: The aim of the this study was to describe changes in head circumference (HC) and cephalic index (CI) in children with sagittal suture synostosis before surgery, by putting the child to bed in supine position lying on the back of the head.

Materials And Methods: A total of 83 patients were scheduled for minimally invasive spring-assisted correction at age 5 to 6 months. At presentation, parents were advised to place their child in bed lying on the back of their head.

Gain-of-Function Mutations in ZIC1 Are Associated with Coronal Craniosynostosis and Learning Disability.

Human ZIC1 (zinc finger protein of cerebellum 1), one of five homologs of the Drosophila pair-rule gene odd-paired, encodes a transcription factor previously implicated in vertebrate brain development. Heterozygous deletions of ZIC1 and its nearby paralog ZIC4 on chromosome 3q25.1 are associated with Dandy-Walker malformation of the cerebellum, and loss of the orthologous Zic1 gene in the mouse causes cerebellar hypoplasia and vertebral defects.

Robin sequence: A European survey on current practice patterns.

To provide an overview of current practice patterns with regard to Robin sequence (RS) patients in Europe, a survey was conducted among European clinicians. This online survey consisted of different sections assessing characteristics of the respondent and clinic, definition, diagnosis, treatment, and follow-up. In total, surveys from 101 different European clinics were included in the analysis, and 56 different RS definitions were returned.

Respiratory Distress Following Cleft Palate Repair in Children With Robin Sequence.

Objective The aim of this study is to assess prevalence, severity, and duration of respiratory distress following palatoplasty in children with Robin sequence and to evaluate perioperative management. Design Retrospective chart review study. Data were collected for patients who were born between 2009 and 2012 and underwent palatoplasty in the Sophia Children's Hospital-Erasmus Medical Center.

The formation of the foramen magnum and its role in developing ventriculomegaly and Chiari I malformation in children with craniosynostosis syndromes.

Object: Craniosynostosis syndromes are characterized by prematurely fused skull sutures, however, less is known about skull base synchondroses. This study evaluates how foramen magnum (FM) size, and closure of its intra-occipital synchondroses (IOS) differ between patients with different craniosynostosis syndromes and control subjects; and whether this correlates to ventriculomegaly and/or Chiari malformation type I (CMI), intracranial disturbances often described in these patients.

Methods: Surface area and anterior-posterior (A-P) diameter were measured in 175 3D-CT scans of 113 craniosynostosis patients, and in 53 controls (0-10 years old).

The role of the posterior fossa in developing Chiari I malformation in children with craniosynostosis syndromes.

Objective: Patients with craniosynostosis syndromes are at risk of increased intracranial pressure (ICP) and Chiari I malformation (CMI), caused by a combination of restricted skull growth, venous hypertension, obstructive sleep apnea (OSA), and an overproduction or insufficient resorption of cerebrospinal fluid. This study evaluates whether craniosynostosis patients with CMI have an imbalance between cerebellar volume (CV) and posterior fossa volume (PFV), that is, an overcrowded posterior fossa.

Methods: Volumes were measured in 3D-SPGR T1-weighted MR scans of 28 'not-operated' craniosynostosis patients (mean age: 4.

The occipitofrontal circumference: reliable prediction of the intracranial volume in children with syndromic and complex craniosynostosis.

OBJECT Patients with syndromic and complex craniosynostosis are characterized by the premature fusion of one or more cranial sutures. These patients are at risk for developing elevated intracranial pressure (ICP). There are several factors known to contribute to elevated ICP in these patients, including craniocerebral disproportion, hydrocephalus, venous hypertension, and obstructive sleep apnea.

Frontobiparietal remodeling with or without a widening bridge for sagittal synostosis: comparison of 2 cohorts for aesthetic and functional outcome.

OBJECT Various techniques to correct sagittal synostosis have been described. The authors of this study assess the results of 2 techniques for late complete cranial remodeling and test the hypothesis that adding a widening bridge would improve outcome. METHODS In this retrospective study, the authors evaluated patients with nonsyndromic sagittal synostosis-those who underwent frontobiparietal remodeling (FBR) and those who underwent modified FBR (MFBR) involving the introduction of a bony bridge to increase the width of the skull.

Nasal sequelae of Treacher Collins syndrome.

Objective: This study aimed to determine external and endonasal deformity, and satisfaction with nasal functioning and appearance, in Treacher Collins syndrome.

Study Design: A cross-sectional cohort study was conducted.

Methods: Eleven adult patients with Treacher Collins syndrome were compared with 151 controls in terms of satisfaction with nasal functioning and appearance by means of the Nasal Appearance and Function Evaluation Questionnaire.

Venous hypertension in syndromic and complex craniosynostosis: the abnormal anatomy of the jugular foramen and collaterals.

Unlabelled: Why craniosynostosis patients develop elevated intracranial pressure (ICP) is still a mystery. Our aim was to investigate jugular foramen size and its relation to venous hypertension and elevated ICP. Secondly, we evaluated whether occipital collateral veins develop as a compensatory mechanism for elevated ICP.

A novel mutation in FGFR2.

Craniosynostosis is a congenital anomaly that can occur as an isolated condition or as part of a syndrome. Although several genes are known to cause syndromic craniosynostosis, only 24% can be attributed to known genes. Therefore, it is likely that more mutations and other genes are involved.