Early detection and treatment of obstructive sleep apnoea in infants with Down syndrome: a prospective, non-randomised, controlled, interventional study.

Background: Infants with Down syndrome (DS) are at high risk of obstructive sleep apnoea (OSA) which is associated with neurocognitive dysfunction and behaviour problems. The aim of our study was to evaluate the effect of early OSA treatment in infants with DS on neurocognitive development and behaviour.

Methods: In this prospective, interventional, non-randomised study, 40 infants with DS underwent polysomnography (PSG) every 6 months in room air between 6 and 36 months of age () and were compared to a control group of 40 infants with DS receiving standard of care and a single, systematic PSG in room air at 36 months of age ().

Safety and preliminary efficacy on cognitive performance and adaptive functionality of epigallocatechin gallate (EGCG) in children with Down syndrome. A randomized phase Ib clinical trial (PERSEUS study).

Purpose: Although some caregivers are using epigallocatechin gallate (EGCG) off label in hopes of improving cognition in young adults with Down syndrome (DS), nothing is known about its safety, tolerability, and efficacy in the DS pediatric population. We aimed to evaluate safety and tolerability of a dietary supplement containing EGCG and if EGCG improves cognitive and functional performance.

Methods: A total of 73 children with DS (aged 6-12 years) were randomized.

Psychomotor development in infants and young children with Down syndrome-A prospective, repeated measure, post-hoc analysis.

Children with Down syndrome (DS) show delayed acquisition of cognitive and functional skills compared to typically developing children. The objective of this study was to accurately describe early development of infants and young children (children hereafter) with DS based on a large recent sample. We carried out repeated measure analysis of the global development quotient (GDQ) and developmental age using data from the Assessment of Systematic Treatment with Folinic Acid and Thyroid Hormone on Psychomotor Development of Down Syndrome Young Children (ACTHYF) study (NCT01576705).

Opportunities, barriers, and recommendations in down syndrome research.

Background: Recent advances in medical care have increased life expectancy and improved the quality of life for people with Down syndrome (DS). These advances are the result of both pre-clinical and clinical research but much about DS is still poorly understood. In 2020, the NIH announced their plan to update their DS research plan and requested input from the scientific and advocacy community.

Molecular Rescue of Dyrk1A Overexpression Alterations in Mice with Fontup Dietary Supplement: Role of Green Tea Catechins.

Epigallocatechin gallate (EGCG) is an inhibitor of DYRK1A, a serine/threonine kinase considered to be a major contributor of cognitive dysfunctions in Down syndrome (DS). Two clinical trials in adult patients with DS have shown the safety and efficacy to improve cognitive phenotypes using commercial green tea extract containing EGCG (45% content). In the present study, we performed a preclinical study using FontUp, a new nutritional supplement with a chocolate taste specifically formulated for the nutritional needs of patients with DS and enriched with a standardized amount of EGCG in young mice overexpressing (TgBACDyrk1A).

Methylomic profiling in trisomy 21 identifies cognition- and Alzheimer's disease-related dysregulation.

Background: Trisomy 21 (T21) is associated with intellectual disability that ranges from mild to profound with an average intellectual quotient of around 50. Furthermore, T21 patients have a high risk of developing Alzheimer's disease (AD) early in life, characterized by the presence of senile plaques of amyloid protein and neurofibrillary tangles, leading to neuronal loss and cognitive decline. We postulate that epigenetic factors contribute to the observed variability in intellectual disability, as well as at the level of neurodegeneration seen in T21 individuals.

Growth curves for French people with Down syndrome from birth to 20 years of age.

We present new and complete growth charts for 2,598 healthy French children and adolescents with Down syndrome (DS) from 0 to 20 years old, obtained with highly reliable statistical methods. This study is retrospective and addresses data collected over a period of 12 years, monocentric and with a satisfactory representation of the population nationwide. Final occipito-frontal circumference (OFC) is at the fifth percentile compared to WHO charts, with a drop between 12 and 18 months.

Biallelic Loss-of-Function Variants in AIMP1 Cause a Rare Neurodegenerative Disease.

AIMP1/p43, is a noncatalytic component of the mammalian multi-tRNA synthetase complex that catalyzes the ligation of amino acids to their cognate tRNAs. AIMP1 is largely expressed in the central nervous system, where it is part of the regulatory machine of the neurofilament assembly, playing a crucial role in neuronal development and function. To date, nonsense mutations in AIMP1 have been associated with a primary neurodegenerative disorder consisting of cerebral atrophy, hypomyelination, microcephaly and epilepsy, whereas missense mutations have recently been linked to intellectual disability without neurodegeneration.

Rare coding variants in genes encoding GABA receptors in genetic generalised epilepsies: an exome-based case-control study.

Background: Genetic generalised epilepsy is the most common type of inherited epilepsy. Despite a high concordance rate of 80% in monozygotic twins, the genetic background is still poorly understood. We aimed to investigate the burden of rare genetic variants in genetic generalised epilepsy.

Humanized mouse model of Rasmussen's encephalitis supports the immune-mediated hypothesis.

Rasmussen's encephalitis (RE) is a chronic inflammatory brain disorder that causes frequent seizures and unilateral hemispheric atrophy with progressive neurological deficits. Hemispherectomy remains the only treatment that leads to seizure freedom for this refractory epileptic syndrome. The absence of an animal model of disease has been a major obstacle hampering the development of effective therapies.

Anthropometric charts and congenital anomalies in newborns with Down syndrome.

The objectives of this study were to obtain updated neonatal measurements in French newborns with Down Syndrome (DS) according to their gestational age, and to assess the frequency and distribution of congenital anomalies. Data on congenital malformations, birth weight, birth length and birth occipito-frontal circumference (OFC) according to the gestational age was gathered from 1,030 babies, born between 1980 and 2010. The mean gestational age was 38 weeks from the date of the last menstrual period (LMP) (range: 29-42 weeks).

Epileptiform asymetries and treatment response in juvenile myoclonic epilepsy.

Background: Epileptiform electroencephalogram (EEG) asymmetries are not uncommon in juvenile myoclonic epilepsy (JME) and can contribute to the misdiagnosis of this syndrome. The objective of this study is to further characterize patients with focal or asymmetric epileptiform electroencephalographic abnormalities and more specifically in terms of response to treatment. Controversial data exists in the literature concerning this issue.

A novel locus for idiopathic generalized epilepsy in French-Canadian families maps to 10p11.

Idiopathic generalized epilepsy (IGE) has evidence of a strong genetic etiology. We conducted genomewide linkage analysis for genes responsible for familial IGE in French-Canadian pedigrees. Twenty families segregating autosomal dominant epilepsy were collected.