Novel study design to assess the efficacy and tolerability of antiseizure medications for focal-onset seizures in infants and young children: A consensus document from the regulatory task force and the pediatric commission of the International League against Epilepsy (ILAE), in collaboration with the Pediatric Epilepsy Research Consortium (PERC).

High-quality placebo-controlled drug trials for focal-onset seizures in infants and children younger than 4 years have become increasingly difficult to perform because of eligibility constraints and onerous study designs. Traditional designs used in these populations require a high baseline seizure frequency, two hospitalizations for video-electroencephalography (video-EEG) monitoring, and willingness to accept potential exposure to placebo when the drugs to be tested are usually already available for off-label prescription. To address these constraints, the International League Against Epilepsy (ILAE) regulatory taskforce and the ILAE pediatric commission, in collaboration with the Pediatric Epilepsy Research Consortium (PERC), propose a novel trial design which involves seizure counting by caregivers based on previous video-EEG/video validation of specific seizure semiologies.

VPS51 biallelic variants cause microcephaly with brain malformations: A confirmatory report.

Whole exome sequencing undertaken in two siblings with delayed psychomotor development, absent speech, severe intellectual disability and postnatal microcephaly, with brain malformations consisting of cerebellar atrophy in the eldest affected and hypoplastic corpus callosum in the younger sister; revealed a homozygous intragenic deletion in VPS51, which encodes the vacuolar protein sorting-associated protein, one the four subunits of the Golgi-associated retrograde protein (GARP) and endosome-associated recycling protein (EARP) complexes that promotes the fusion of endosome-derived vesicles with the trans-Golgi network (GARP) and recycling endosomes (EARP). This observation supports a pathogenic effect of VPS51 variants, which has only been reported previously once, in a single child with microcephaly. It confirms the key role of membrane trafficking in normal brain development and homeostasis.

Impact of cancer chemotherapy before ovarian cortex cryopreservation on ovarian tissue transplantation.

Study Question: How efficacious is transplantation of ovarian cortex previously exposed to chemotherapy?

Summary Answer: Prior exposure to chemotherapy did not disrupt the function of cryopreserved ovarian tissue after transplantation.

What Is Known Already: Ovarian tissue cryopreservation (OTC) followed by ovarian tissue transplantation (OTT) is an efficacious technique for restoration of female fertility. At least 130 children have been born following this procedure.

EFNB2 haploinsufficiency causes a syndromic neurodevelopmental disorder.

Ephrin B2, one of the ligand of the EphB receptors, is involved in a complex signaling pathway regulating the development of the nervous system, neuronal migration, erythropoiesis and vasculogenesis. We report a patient with a de novo variant in EFNB2 and a family in which segregates a 610-kb deletion at chromosome 13q33 encompassing only ARGLU1 and EFNB2 genes. The de novo variant was observed in a patient with anal stenosis, hypoplastic left ventricle and mild developmental delay.

Mutations in RIT1 cause Noonan syndrome with possible juvenile myelomonocytic leukemia but are not involved in acute lymphoblastic leukemia.

Noonan syndrome is a heterogeneous autosomal dominant disorder caused by mutations in at least eight genes involved in the RAS/MAPK signaling pathway. Recently, RIT1 (Ras-like without CAAX 1) has been shown to be involved in the pathogenesis of some patients. We report a series of 44 patients from 30 pedigrees (including nine multiplex families) with mutations in RIT1.

Paediatric arterial ischemic stroke: acute management, recent advances and remaining issues.

Stroke is a rare disease in childhood with an estimated incidence of 1-6/100.000. It has an increasingly recognised impact on child mortality along with its outcomes and effects on quality of life of patients and their families.

Variable expression pattern in Donnai-Barrow syndrome: Report of two novel LRP2 mutations and review of the literature.

Donnai-Barrow syndrome (DBS; MIM 222448) is characterized by typical craniofacial anomalies (major hypertelorism with bulging eyes), high grade myopia, deafness and low molecular weight proteinuria. The disorder results from mutations in the low density lipoprotein receptor-related protein 2 gene LRP2 that maps to chromosome 2q31.1.

A new lysosomal storage disorder resembling Morquio syndrome in sibs.

We report two male sibs, born from unrelated French Caribbean parents, presenting with an unclassifiable storage disorder. Pregnancy and delivery were uneventful. Stunted growth was noted during the first year of life.

Craniosynostosis: A rare complication of pycnodysostosis.

Uncommon features of rare genetic disorders are often poorly known, as the likelihood of having them reported is low. We describe a 7-year-old boy with clinical and radiological diagnosis of pycnodysostosis, and c.436G>C (p.

Ectodermal dysplasia-like syndrome with mental retardation due to contiguous gene deletion: further clinical and molecular delineation of del(2q32) syndrome.

We report on a patient with an interstitial deletion of the long arm of chromosome 2 at 2q31.2q33.2.

The spectrum of cardiac anomalies in Noonan syndrome as a result of mutations in the PTPN11 gene.

Objective: Noonan syndrome is a clinically homogeneous but genetically heterogeneous condition. Type 1 Noonan syndrome is defined by the presence of a mutation in the PTPN11 gene, which is found in approximately 40% of the cases. Phenotype descriptions and cardiac defects from cohorts with Noonan syndrome were delineated in the "pregenomic era.