Characterizing Daily-Life Social Interactions in Adolescents and Young Adults with Neurodevelopmental Disorders: A Comparison Between Individuals with Autism Spectrum Disorders and 22q11.2 Deletion Syndrome

Social impairments are common features of 22q11.2 deletion syndrome (22q11DS) and autism spectrum disorders (ASD). The Ecological Momentary Assessment (EMA) allowed access to daily-life information in order to explore the phenomenology of social interactions. 32 individuals with 22q11DS, 26 individuals with ASD and 44 typically developing peers (TD) aged 12–30 were assessed during 6 days 8 times a day using a mobile app. Participants with 22q11DS and ASD did not spend more time alone but showed distinct implication in the social sphere than TD. Distinct profiles emerged between the two conditions regarding the subjective experience of aloneness and the subjective experience of social interactions. This study highlights distinct social functioning profiles in daily-life in 22q11DS and ASD that points towards different therapeutic targets.

Analysis Of Rem Sleep Without Atonia In 22q11.2 Deletion Syndrome Determined By Domiciliary Polysomnography: A Cross Sectional Study

Study Objectives Our aim is to evaluate the presence of REM sleep without atonia (RWA), the objective hallmark of REM sleep Behaviour Disorder (RBD), as prodromal marker of Parkinson’s disease (PD), in an adult cohort of 22q11.2 deletion syndrome (22qDS). Methods Sleep quality was assessed by means of Pittsburgh quality scale index (PSQI), and RBD symptoms by means of RBD questionnaire-Hong-Kong (RBDQ-HK). Attended domiciliary video-Polysomnography (v-PSG) were performed in 26 adults (18-51 years, 14 females) 22qDS patients. Electromyogram during REM sleep was analyzed by means of SINBAR procedure at 3-second time resolution (miniepochs). Results An overall poor sleep quality was observed in the cohort and high RBDQ-HK score in 7 of the 26 patients, two additional patients with positive dream enactment reported by close relatives had low score of RBDQ-HK. Nevertheless, SINBAR RWA scores were lower than cut-off threshold for RWA (mean 5.5%, range 0%-12.2%). TST and the percentage of light sleep (N1) were increased, with preserved proportions of N2 and N3. Participants reported poor quality of sleep (mean PSQI>5), with prolonged sleep latency in the v-PSG. No subjects exhibit evident dream enactment episodes during recording sessions. Conclusions RWA was absent in the studied cohort of 22qDS adult volunteers according to validated polysomnographic criteria. High RBDQ-HK scores do not correlate with v-PSG results among 22qDS individuals.

Variability of CATCH-22 symptome complex within the framework of 22q11.2 deletion syndrome

Chromosomal pathology is one of the most common causes of congenital malformations. The CATCH-22 symptom complex is most often associated with a microdeletion of chromosome 22, upon detection of which it is customary to diagnose DiGeorge syndrome, a known primary immunodeficiency or syndrome of innate errors of immunity. According to our data on the frequency of occurrence among all chromosomal abnormalities, DiGeorge’s syndrome takes second place in the Sverdlovsk region after Down’s syndrome, but its diagnosis is not simple due to varying severity of clinical manifestations, as well as different forms of the chromosome 22 defects. Along with several typical variants of 22q11 microdeletions, there duplications of critical regions are also reported, accompanied by immunodeficiency and other symptoms of CATCH-22. The effectiveness of diagnosing chromosomal abnormalities both in pre- and postnatal period largely depends on the grouping criteria of the patients with suspected chromosomal abnormalities, and on the methods used to identify hereditary pathology. In our study, we analyzed and compared the results of studies of 23 patients with various rearrangements of the 22q11.2 region, which were observed by a geneticist and clinical immunologist. The paper presents data on the polymorphism of phenotypes associated with rearrangements of the 22q11.2 region with an analysis of pathomorphological manifestations depending on the type of structural anomaly, i.e, del22q11.2, or dup22q11.2. The results of analysis demonstrate importance of different diagnostic options for laboratory studies of microdeletion and microduplication syndromes associated with immune-dependent pathology. We also compared the results of molecular genetic diagnostics and phenotypic manifestations in deletions and duplications of the 22q11.2 region. To identify the rearrangements of 22q11.2 region, two different methods were used – Prenatal BoBs and multiplex ligase-dependent probes’ amplification (MLPA). In particular, the both methods were used in the same patient to verify diagnosis, thus enabling to show differences in their efficiency. It was concluded that 22q11.2 deletion syndrome exhibits wide heterogeneity in phenotypic traits: neurological and immunological manifestations, anomalies in musculoskeletal development and internal organs, skull deformities and facial dysmorphia. Each clinical case was unique, requiring careful analysis of clinical manifestations. It is necessary to have a wide range of laboratory options for molecular genetic verification of the diagnosis.

Neural networks for classification and image generation of aging in genetic syndromes

In medical genetics, one application of neural networks is the diagnosis of genetic diseases based on images of patient faces. While these applications have been validated in the literature with primarily pediatric subjects, it is not known whether these applications can accurately diagnose patients across a lifespan. We aimed to extend previous works to determine whether age plays a factor in facial diagnosis, as well as to explore other factors that may contribute to the overall diagnosis accuracy. To investigate this, we chose two relatively common conditions, Williams syndrome and 22q11.2 deletion syndrome. We built a neural network classifier trained on images of affected and unaffected individuals of different ages. Our classifier outperformed clinical geneticists at recognizing face images of these two conditions within each of the age groups (the performance varied between the age groups): (1) under 2 years old, (2) 2-9 years old, (3) 10-19 years old, (4) 20-34 years old, and (5) ≥35 years old. The overall accuracy improvement by our classifier over the clinical geneticists was 15.5% and 22.7% for Williams syndrome and 22q11.2 deletion syndrome, respectively. Additionally, comparison of saliency maps revealed that key facial features learned by the neural network differed slightly with respect to age. Finally, joint training real images with multiple different types of fake images created by a generative adversarial network showed up to 3.25% accuracy gain in classification accuracy.

A Case for Thalamic Mechanisms of Schizophrenia: Perspective From Modeling 22q11.2 Deletion Syndrome

Schizophrenia is a severe, chronic psychiatric disorder that devastates the lives of millions of people worldwide. The disease is characterized by a constellation of symptoms, ranging from cognitive deficits, to social withdrawal, to hallucinations. Despite decades of research, our understanding of the neurobiology of the disease, specifically the neural circuits underlying schizophrenia symptoms, is still in the early stages. Consequently, the development of therapies continues to be stagnant, and overall prognosis is poor. The main obstacle to improving the treatment of schizophrenia is its multicausal, polygenic etiology, which is difficult to model. Clinical observations and the emergence of preclinical models of rare but well-defined genomic lesions that confer substantial risk of schizophrenia (e.g., 22q11.2 microdeletion) have highlighted the role of the thalamus in the disease. Here we review the literature on the molecular, cellular, and circuitry findings in schizophrenia and discuss the leading theories in the field, which point to abnormalities within the thalamus as potential pathogenic mechanisms of schizophrenia. We posit that synaptic dysfunction and oscillatory abnormalities in neural circuits involving projections from and within the thalamus, with a focus on the thalamocortical circuits, may underlie the psychotic (and possibly other) symptoms of schizophrenia.