A large cohort study of prenatal exome sequencing redefines diagnosis in fetal corpus callosum anomalies.

Anomalies of the corpus callosum (AnCC) are congenital malformations associated with highly variable neurodevelopmental outcomes. We performed prenatal Exome Sequencing (pES) on a cohort of 352 fetuses diagnosed with AnCC, analyzing the diagnostic yield, the implicated genes based on the type of anomaly (partial or complete agenesis, short corpus callosum, or callosal dysgenesis) and assessing the impact on pregnancy outcomes. The overall diagnostic yield of pES was 23%, with pathogenic or likely pathogenic variants identified in 49 different genes, most of which linked to intellectual developmental disorders.

Pathogenic Variants Cause Obstructive Ventriculomegaly Related to Diencephalosynapsis and Third Ventricle Atresia.

Objective: Ventriculomegaly is the main prenatal imaging feature for diagnosing fetal central nervous system anomalies in humans. Many ventriculomegalies can be related to genetic causes, regardless of their imaging presentations. Among these, variants have been reported to cause severe ventriculomegaly inherited in an autosomal recessive manner (OMIM#615219).

Antiseizure effect of MEK inhibitor in a child with neurofibromatosis type 1-Developmental and epileptic encephalopathy and optic pathway glioma.

Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant genetic disorder due to a mutation in NF1 gene, resulting in phenotypically heterogeneous systemic manifestations. Patients with NF1 are prone to develop neoplasms of the central nervous system (CNS) and are particularly at risk for optic pathway gliomas (OPG). Epilepsy is another recognized neurologic complication in patients with NF1, with a prevalence estimated between 4% and 14%.

Drosophila functional screening of de novo variants in autism uncovers damaging variants and facilitates discovery of rare neurodevelopmental diseases.

Individuals with autism spectrum disorder (ASD) exhibit an increased burden of de novo mutations (DNMs) in a broadening range of genes. While these studies have implicated hundreds of genes in ASD pathogenesis, which DNMs cause functional consequences in vivo remains unclear. We functionally test the effects of ASD missense DNMs using Drosophila through "humanization" rescue and overexpression-based strategies.

Multisystem disorders, severe developmental delay and seizures in two affected siblings, expanding the phenotype of PIGC deficiency.

PIGC (OMIM 601730) encodes the PIGC protein, which is part of an enzyme complex involved in the biosynthesis of the glycosylphosphatidylinositol protein anchor. The other proteins in the complex include PIGA, PIGH, PIGQ, PIGY, PIGP and DPM2. Homozygous and compound heterozygous mutations in PIGC have recently been described to cause severe global developmental delay, intellectual disability, and seizures in two unrelated families, without indication of another system involvement or dysmorphism.

Clinical and molecular description of 19 patients with GATAD2B-Associated Neurodevelopmental Disorder (GAND).

De novo pathogenic variants in the GATAD2B gene have been associated with a syndromic neurodevelopmental disorder (GAND) characterized by severe intellectual disability (ID), impaired speech, childhood hypotonia, and dysmorphic features. Since its first description in 2013, nine patients have been reported in case reports and a series of 50 patients was recently published, which is consistent with the relative frequency of GATAD2B pathogenic variants in public databases. We report the detailed phenotype of 19 patients from various ethnic backgrounds with confirmed pathogenic GATAD2B variants including intragenic deletions.

Repair of Cranial Bone Defects in Children Using Synthetic Hydroxyapatite Cranioplasty (CustomBone).

Background: In pediatric cases, the use of autologous bone tissue to repair cranial bone defects is often impossible. The synthetic hydroxyapatite bone substitute (CustomBone) can be a good alternative, especially in case of a large bone defect that has to be repaired.

Methods: This study focuses on a pediatric series of 30 children who underwent cranioplasty with a CustomBone implant.

Variants in TCF20 in neurodevelopmental disability: description of 27 new patients and review of literature.

Purpose: To define the clinical characteristics of patients with variants in TCF20, we describe 27 patients, 26 of whom were identified via exome sequencing. We compare detailed clinical data with 17 previously reported patients.

Methods: Patients were ascertained through molecular testing laboratories performing exome sequencing (and other testing) with orthogonal confirmation; collaborating referring clinicians provided detailed clinical information.

Isolated Antenatal Hydrocephalus After Fetal Exposure to Misoprostol: Teratogenic Effect of the Cytotec?

Background: Misoprostol is often used for termination of pregnancy in France and other countries. However, some pregnancies are continued after taking the drug and congenital malformations are known to be the consequence of fetal exposure to misoprostol, among them hydrocephalus. The type of hydrocephalus in case of misoprostol exposure is not known.

A Recurrent De Novo PACS2 Heterozygous Missense Variant Causes Neonatal-Onset Developmental Epileptic Encephalopathy, Facial Dysmorphism, and Cerebellar Dysgenesis.

Developmental and epileptic encephalopathies (DEEs) represent a large clinical and genetic heterogeneous group of neurodevelopmental diseases. The identification of pathogenic genetic variants in DEEs remains crucial for deciphering this complex group and for accurately caring for affected individuals (clinical diagnosis, genetic counseling, impacting medical, precision therapy, clinical trials, etc.).

Postnatal Management of Myelomeningocele: Outcome with a Multidisciplinary Team Experience.

Introduction: Myelomeningocele (MMC) is a complex neural tube defect. Few studies report the results of modern postnatal management. The goal of this study was to report the long-term outcome of a multidisciplinary approach of patients with MMC.

Complete Reversibility of the Chiari Type II Malformation After Postnatal Repair of Myelomeningocele.

Objective: It was believed that Chiari type II malformation (CM-II) was always present in a myelomeningocele (MMC). In fact, it is associated in about 80% of cases. Improvement of the hindbrain herniation after prenatal closure of MMC has challenged the idea that this condition was irreversible.

Stroke by carotid artery complete occlusion in Kawasaki disease: case report and review of literature.

Background: Kawasaki disease is an acute and time-limited systemic vasculitis primarily affecting young children.

Patient: We describe an 18-month-old girl with Kawasaki disease who developed cerebral infarction following complete occlusion of her right internal carotid artery.

Results: The occlusion occurred 10 days after the onset of fever, while she was on high-dose aspirin, and the day after she received intravenous immunoglobulin treatment.