Clinical impact of subcutaneous treprostinil in trisomy 21 patient with pulmonary arterial hypertension associated with CHD

Subcutaneous treprostinil is commonly used to improve idiopathic pulmonary arterial hypertension in children. However, its effectiveness has not been reported in trisomy 21. We report the case of 9-year-old boy in trisomy 21 with CHD-pulmonary artery hypertension after surgical correction of CHD. Haemodynamics and exercise capacity dramatically improved with a transition from oral selexipag to subcutaneous treprostinil.

Sonic Hedgehog Pathway Modulation Normalizes Expression of Olig2 in Rostrally Patterned NPCs With Trisomy 21

The intellectual disability found in people with Down syndrome is associated with numerous changes in early brain development, including the proliferation and differentiation of neural progenitor cells (NPCs) and the formation and maintenance of myelin in the brain. To study how early neural precursors are affected by trisomy 21, we differentiated two isogenic lines of induced pluripotent stem cells derived from people with Down syndrome into brain-like and spinal cord-like NPCs and promoted a transition towards oligodendroglial fate by activating the Sonic hedgehog (SHH) pathway. In the spinal cord-like trisomic cells, we found no difference in expression of OLIG2 or NKX2.2, two transcription factors essential for commitment to the oligodendrocyte lineage. However, in the brain-like trisomic NPCs, OLIG2 is significantly upregulated and is associated with reduced expression of NKX2.2. We found that this gene dysregulation and block in NPC transition can be normalized by increasing the concentration of a SHH pathway agonist (SAG) during differentiation. These results underscore the importance of regional and cell type differences in gene expression in Down syndrome and demonstrate that modulation of SHH signaling in trisomic cells can rescue an early perturbed step in neural lineage specification.

Prevalence of common aneuploidy in twin pregnancies

The incidence of chromosomal abnormalities in twin pregnancies is not well-studied. In this retrospective study, we investigated the frequency of chromosomal abnormalities in twin pregnancies and compared the incidence of chromosomal abnormalities in dichorionic diamniotic (DD) and monochorionic diamniotic (MD) twins. We used data from 57 clinical facilities across Japan. Twin pregnancies of more than 12 weeks of gestation managed between January 2016 and December 2018 were included in the study. A total of 2899 and 1908 cases of DD and MD twins, respectively, were reported, and the incidence of chromosomal abnormalities in one or both fetuses was 0.9% (25/2899) and 0.2% (4/1908) in each group (p = 0.004). In this study, the most common chromosomal abnormality was trisomy 21 (51.7% [15/29]), followed by trisomy 18 (13.8% [4/29]) and trisomy 13 (6.9% [2/29]). The incidence of trisomy 21 in MD twins was lower than that in DD twins (0.05% vs. 0.5%, p = 0.007). Trisomy 21 was less common in MD twins, even when compared with the expected incidence in singletons (0.05% vs. 0.3%, RR 0.15 [95% CI 0.04–0.68]). The risk of chromosomal abnormality decreases in twin pregnancies, especially in MD twins.

Value of Nuchal Translucency in Detection of Chromosomal Aberration in Vietnam Population

Objective: To examine the sensitivity and specificity of different thresholds of nuchal translucency in diagnosis of chromosomal defects. Study Design: This is a longitudinal study of pregnant women have first trimester screening and ultrasound in center of diagnostic antenatal of national hospital of obstetrics and gynecology. A follow-up was made to identify, in all singleton pregnancies in both group of which fetal karyotyping was made and group of normal fetuses. The threshold for nuchal translucency was divided in to above the 95th percentile, the 99th percentile, the 3.0mm and 2.5 MoM of nuchal translucency. The sensitivity and specificity ware calculated in order to diagnosis the chromosomal abbreviation. Results: The research identified 2645 fetuses, 743 amniocentesis (28%). There is 32.4% fetus has NT ≥ the 95th percentile, 28.6% ≥ 2.5mm percentile, 22.3% ≥ 3.0mm, 16.6% above 2.5 MoM. The fetal karyotype was abnormal in 157 (5.8%) pregnancies. The popular conditions were found including trisomy 21(52.2%). Then structural rearrangements occupied 31.2%. Other chromosomes like 13,18,21 occupied 12.7%. The abnormal of sex chromosome was smallest proportion with only 3.8%. At the 95th percentile of nuchal translucency has the highest sensitivity in detection of chromosomal defects (99.4%) but the threshold 2.5mm has a better detection rate (20.4%). The cut off 3.0mm has a better positive prediction rate (22.3%) but could detect less defects (only 132/157 abbreviation). The threshold 2.5xMoM had the highest specificity (86.4%) but lowest sensitivity (only 65%). Conclusion: In fetuses with increased nuchal translucency, more than a half of the chromosomally abnormal group is affected by defects other than trisomy 21 (52.2%). Using threshold 2.5mm helps detect more 23 chromosomal defects in comparison with the threshold 3.0mm and it had the highest average of sensitivity and specificity (87.25%).

A New Socially Assistive Robot with Integrated Serious Games for Therapies with Children with Autism Spectrum Disorder and Down Syndrome: A Pilot Study

This work introduces a new socially assistive robot termed MARIA T21 (meaning “Mobile Autonomous Robot for Interaction with Autistics”, with the addition of the acronym T21, meaning “Trisomy 21”, which is used to designate individuals with Down syndrome). This new robot is used in psychomotor therapies for children with Down syndrome (contributing to improve their proprioception, postural balance, and gait) as well as in psychosocial and cognitive therapies for children with autism spectrum disorder. The robot uses, as a novelty, an embedded mini-video projector able to project Serious Games on the floor or tables to make already-established therapies funnier to these children, thus creating a motivating and facilitating effect for both children and therapists. The Serious Games were developed in Python through the library Pygame, considering theoretical bases of behavioral psychology for these children, which are integrated into the robot through the robot operating system (ROS). Encouraging results from the child–robot interaction are shown, according to outcomes obtained from the application of the Goal Attainment Scale. Regarding the Serious Games, they were considered suitable based on both the “Guidelines for Game Design of Serious Games for Children” and the “Evaluation of the Psychological Bases” used during the games’ development. Thus, this pilot study seeks to demonstrate that the use of a robot as a therapeutic tool together with the concept of Serious Games is an innovative and promising tool to help health professionals in conducting therapies with children with autistic spectrum disorder and Down syndrome. Due to health issues imposed by the COVID-19 pandemic, the sample of children was limited to eight children (one child with typical development, one with Trisomy 21, both female, and six children with ASD, one girl and five boys), from 4 to 9 years of age. For the non-typically developing children, the inclusion criterion was the existence of a conclusive diagnosis and fulfillment of at least 1 year of therapy. The protocol was carried out in an infant psychotherapy room with three video cameras, supervised by a group of researchers and a therapist. The experiments were separated into four steps: The first stage was composed of a robot introduction followed by an approximation between robot and child to establish eye contact and assess proxemics and interaction between child/robot. In the second stage, the robot projected Serious Games on the floor, and emitted verbal commands, seeking to evaluate the child’s susceptibility to perform the proposed tasks. In the third stage, the games were performed for a certain time, with the robot sending messages of positive reinforcement to encourage the child to accomplish the game. Finally, in the fourth stage, the robot finished the games and said goodbye to the child, using messages aiming to build a closer relationship with the child.

Folate pathway metabolites are altered in the plasma of subjects with Down syndrome: relation to chromosomal dosage

Down syndrome (DS) is the most common chromosomal disorder, and it is caused by trisomy of chromosome 21 (Hsa21). Subjects with DS can show a large heterogeneity of phenotypes and congenital defects and the most constant clinical features present are typical facies and intellectual disability (ID). Jérôme Lejeune was the first who hypothesized that DS could be a metabolic disease and he noted an alteration of the folate pathway (part of the one-carbon cycle) in trisomic cell lines and subjects with DS. Comparing DS with other metabolic diseases characterized by ID and altered folate pathway he hypothesized a possible correlation among them. Recently, a nuclear magnetic resonance (NMR) analysis of the detectable metabolic part in plasma and urine samples was performed, comparing a group of subjects with DS and a group of control subjects. The data showed a clear difference in the concentration of some metabolites (all involved in central metabolic processes) for the DS group, which was sometimes in agreement with gene dosage expected proportions (3:2). The aim of this work is to underline metabolic differences between subjects with DS and control subjects in order to better understand the dysregulation of the folate pathway in DS. For the first time, we performed enzyme-linked immunosorbent assays (ELISAs) to identify the concentration of 4 different intermediates of the one-carbon cycle, namely tetrahydrofolate (THF), 5-methyl-THF, 5-formyl-THF and S-adenosyl-homocysteine (SAH) in plasma samples obtained from 153 subjects with DS and 54 euploid subjects. Results highlight specific alterations of some folate pathway related metabolites. The relevance of these results for the biology of intelligence and its impairment in trisomy 21 is discussed leading to the proposal of 5-methyl-THF as the best candidate for a clinical trial aimed at restoring the dysregulation of folate pathway in trisomy 21 and improving cognitive skills of subjects with DS.