The role of pathogenic TCF12 variants in children with coronal craniosynostosis-a systematic review with addition of two novel cases.

Craniosynostosis constitutes one of the most common congenital cranial malformations, affecting approximately 6/10,0000 live births. A genetic etiology has long been known for several forms of syndromic craniosynostosis, including pathogenic variants in TWIST1 and FGFR3 in children with Saethre-Chotzen and Muenke syndrome. Over the last decade, reports of genetic aberrations in TCF12 in children with craniosynostosis have emerged, in particular in cases with premature closure of the coronal suture(s).

The evolutionary impact of childhood cancer on the human gene pool.

Germline pathogenic variants associated with increased childhood mortality must be subject to natural selection. Here, we analyze publicly available germline genetic metadata from 4,574 children with cancer [11 studies; 1,083 whole exome sequences (WES), 1,950 whole genome sequences (WGS), and 1,541 gene panel] and 141,456 adults [125,748 WES and 15,708 WGS]. We find that pediatric cancer predisposition syndrome (pCPS) genes [n = 85] are highly constrained, harboring only a quarter of the loss-of-function variants that would be expected.

Thirty-day surgical morbidity and risk factors in pediatric brain tumor surgery: a 10-year nationwide retrospective study.

Objective: Pediatric neuro-oncological surgery is often associated with significant risk; however, comprehensive data on surgical morbidity remain limited. The purpose of this study was therefore to provide national population-based data on both the incidence and characteristics of poor postoperative outcomes following pediatric intracranial neuro-oncological surgery. Additionally, the authors aimed to evaluate key risk factors for poor postoperative outcomes including overall morbidity, significant morbidity, and the most frequent types of morbidity.

Germline (epi)genetics reveals high predisposition in females: a 5-year, nationwide, prospective Wilms tumour cohort.

Background: Studies suggest that Wilms tumours (WT) are caused by underlying genetic (5%-10%) and epigenetic (2%-29%) mechanisms, yet studies covering both aspects are sparse.

Methods: We performed prospective whole-genome sequencing of germline DNA in Danish children diagnosed with WT from 2016 to 2021, and linked genotypes to deep phenotypes.

Results: Of 24 patients (58% female), 3 (13%, all female) harboured pathogenic germline variants in WT risk genes ( and ).

Assessment of the Milan Complexity Scale for prediction of postoperative morbidity in pediatric neuro-oncological surgery.

Purpose: To assess the performance of the risk-predicting Milan Complexity Scale (MCS) on postoperative morbidity in pediatric neuro-oncological surgery.

Methods: A retrospective dual-center review of children undergoing primary brain tumor resection in Denmark over a 10-year period. MCS scoring was performed based on preoperative imaging, blinded to individual outcomes.

Multi-ancestry genome-wide association study of 4069 children with glioma identifies 9p21.3 risk locus.

Background: Although recent sequencing studies have revealed that 10% of childhood gliomas are caused by rare germline mutations, the role of common variants is undetermined and no genome-wide significant risk loci for pediatric central nervous system tumors have been identified to date.

Methods: Meta-analysis of 3 population-based genome-wide association studies comprising 4069 children with glioma and 8778 controls of multiple genetic ancestries. Replication was performed in a separate case-control cohort.

CNS infection in children with brain tumors: adding ventriculostomy to brain tumor resection increases risk more than 20-fold.

Purpose: To investigate the risk of central nervous system (CNS) infections in children undergoing neurosurgery for brain tumors.

Methods: Single-center retrospective cohort study including all children with brain tumors undergoing neurosurgical treatment over an 11-year period.

Results: A total of 274 patients undergoing 733 neurosurgical procedures were included.

The current understanding of germline predisposition in non-syndromic sagittal craniosynostosis: a systematic review.

Purpose: The objective of this literature review was to provide a comprehensive and up-to-date overview of the current understanding of the genetic etiology for non-syndromic sagittal craniosynostosis.

Methods: Using the PubMed database and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), we systematically reviewed relevant records on germline genetics in children with non-syndromic sagittal craniosynostosis.

Results: Two hundred two records were identified, of which 25 were included following title and abstract screening and subsequent full-text review.

Redefining germline predisposition in children with molecularly characterized ependymoma: a population-based 20-year cohort.

Ependymoma is the second most common malignant brain tumor in children. The etiology is largely unknown and germline DNA sequencing studies focusing on childhood ependymoma are limited. We therefore performed germline whole-genome sequencing on a population-based cohort of children diagnosed with ependymoma in Denmark over the past 20 years (n = 43).

Genetic predisposition to central nervous system tumors in children - what the neurosurgeon should know.

Background: Historically, few pediatric central nervous system (CNS) tumors were thought to result from genetic predisposition. However, within the last decade, new DNA sequencing methods have led to an increased recognition of high-risk cancer predisposition syndromes in children with CNS tumors. Thus, genetic predisposition is increasingly impacting clinical pediatric neuro-oncology.

Genome-wide association study across pediatric central nervous system tumors implicates shared predisposition and points to 1q25.2 (PAPPA2) and 11p12 (LRRC4C) as novel candidate susceptibility loci.

Introduction: Central nervous system (CNS) tumors constitute the most common form of solid neoplasms in children, but knowledge on genetic predisposition is sparse. In particular, whether susceptibility attributable to common variants is shared across CNS tumor types in children has not been investigated. The purpose of this study was to explore potential common genetic risk variants exhibiting pleiotropic effects across pediatric CNS tumors.

Intracranial pressure, brain morphology and cognitive outcome in children with sagittal craniosynostosis.

Background: Patients with sagittal craniosynostosis are at increased risk of developing raised intracranial pressure (ICP) and neurocognitive deficiencies such as reduced attention, planning, speech, behavioural and learning disabilities.

Aim: To determine if the existing literature supports a correlation between elevated ICP and negative cognitive outcome in patients with sagittal craniosynostosis. Secondly, to investigate if the risk of developing neurocognitive deficiencies can be explained by changes in brain morphology in this patient category.

[Topical haemostatic agents in neurosurgery].

Haemostasis is of fundamental significance in neurosurgery, and insufficient control of bleeding is associated with morbidity and mortality. Topical haemostatic agents play an important role, as the characteristics of neuronal tissue limit the use of classical surgical haemostasis techniques. Appropriate choice of agent depends on the location and type of bleeding, but also on knowledge of the products' mechanisms of action, indications, price and accessibility.

Transient global amnesia after cerebral angiography still occurs: Case report and literature review.

Transient global amnesia is considered a very rare complication of diagnostic cerebral angiography, and has been reported only in a limited number of case reports more than 15 years ago. We describe a patient experiencing transient global amnesia following cerebral digital subtraction angiography. While the condition by definition is self-limiting, its differential diagnoses may cause severe morbidity and/or mortality if left untreated.

Childhood hydrocephalus - is radiological morphology associated with etiology.

Background: Clinicians use a non-standardized, intuitive approach when correlating radiological morphology and etiology of hydrocephalus.

Objective: To investigate the possibility of categorizing hydrocephalus in different groups based on radiological morphology, to analyze if these proposed groups relate to the location and type of underlying pathology, and if this can be of use in clinical practice.

Methods And Material: A retrospective cohort study including 110 hydrocephalus patients below age seven seen at Rigshospitalet University Hospital, Denmark.