Multiple Developmental Disorders Research Articles

О конференции, посвященной 100-летию А.И.Мещерякова

<p>On December 19, 2023, the National Scientific and Practical conference with international participation “Comprehensive support for children and young people with disabilities with complex sensory and multiple developmental disorders (To the 100th anniversary of Alexander Ivanovich Meshcheryakov)” was held at the A.I. Meshcheryakov Family Center, Sergiev Posad, Russia. The reports presented at the conference highlighted the current problems of studying complex developmental disorders and contributed to the exchange of experience between the conference participants in organizing and providing assistance to children and adults with congenital complex sensory and multiple developmental disabilities.</p>

Transcriptome research of human amniocytes identifies hub genes associated with developmental dysplasia in down syndrome.

Trisomy 21, or Down syndrome (DS), is the most frequent human autosomal chromosome aneuploidy, which leads to multiple developmental disorders, especially mental retardation in individuals. The presence of an additional human chromosome 21 (HSA21) could account for the pathological manifestations in DS. In this study, we analyzed the mRNA gene expression profile of DS-derived amniocytes compared with normal amniocytes, aiming to evaluate the relationship between candidate dysregulated HSA21 genes and DS developmental phenotypes. Differentially expressed genes (DEGs) included 1794 upregulated genes and 1411 downregulated genes, which are mainly involved in cell adhesion, inflammation, cell proliferation and thus may play an important role in inducing multiple dysplasia during DS fetal development. Furthermore, STRING protein network studies demonstrated 7 candidate HSA21 genes participated Gene Ontology (GO) terms: cell adhesion and extracellular matrix remodeling (COL6A1, COL6A2, COL18A1, ADAMTS5, JAM2, and POFUT2), inflammation and virus infection response (MX1 and MX2), histone modification and chromatin remodeling (NRIP1), glycerolipid and glycerophospholipid metabolism (AGPAT3), mitochondrial function (ATP5PF and ATP5PO), synaptic vesicle endocytosis (ITSN1 and SYNJ1) and amyloid metabolism (APP). Meanwhile, GSEA enrichment identified several transcription factors and miRNAs, which may target gene expression in the DS group. Our study established connections between dysregulated genes, especially HSA21 genes, and DS-associated phenotypes. The alteration of multiple pathways and biological processes may contribute to DS developmental disorders, providing potential pathogenesis and therapeutic targets for DS.

Two-headed parthenogenetic lizard embryo from southern Georgia

Abstract Visual inspection of several embryos of the parthenogenetic lizard Darevskia armeniaca revealed the presence of an embryo with axial bifurcation (“two-headed”) on the stage of pigmented eyes and plate-like limb buds with a distinct border at the edges. This is the third recorded case of axial bifurcation in D. armeniaca, although two previous cases were mentioned without further discussion. Here the bicephalic embryo is described in detail and the potential reasons are discussed. The analysis of the literature on axial bifurcation in lacertids suggests that this type of developmental disorder may be particularly common in this parthenogenetic form. Hybridization may cause multiple developmental disorders, including incomplete separation of twin embryos; all parthenogenetic Darevskia have a hybrid origin, and this may cause the disorders rather than parthenogenetic reproduction by itself. The hypothesis needs further study with more representative samples of parthenogenetic and sexually reproducing Darevskia.

Abstract A026: Stochastic phenotypes in RAS-dependent developmental diseases

Abstract Germline mutations upregulating RAS signaling are associated with multiple developmental disorders. A hallmark of these conditions is that the same mutation may present vastly different phenotypes in different individuals, even in monozygotic twins. We demonstrate how the origins of such largely unexplained phenotypic variations may be dissected using highly controlled studies in Drosophila that have been gene edited to carry activating variants of MEK, a core enzyme in the RAS pathway. This allowed us to measure the small but consistent increase in signaling output of such alleles in vivo. The fraction of mutation carriers reaching adulthood was strongly reduced, but most surviving animals had normal RAS-dependent structures. We rationalize these results using a stochastic signaling model and support it by quantifying cell fate specification errors in bilaterally symmetric larval trachea, a RAS-dependent structure that allows us to isolate the effects of mutations from potential contributions of genetic modifiers and environmental differences. We propose that the small increase in signaling output shifts the distribution of phenotypes into a regime, where stochastic variation causes defects in some individuals, but not in others. Our findings shed light on phenotypic heterogeneity of developmental disorders caused by deregulated RAS signaling and offer a framework for investigating causal effects of other pathogenic alleles and mild mutations. Citation Format: Robert A. Marmion, Alison G. Simpkins, Lena A. Barrett, Jodi Schottenfeld-Roames, Trudi Schüpbach, Stanislav Y. Shvartsman. Stochastic phenotypes in RAS-dependent developmental diseases [abstract]. In: Proceedings of the AACR Special Conference: Targeting RAS; 2023 Mar 5-8; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Res 2023;21(5_Suppl):Abstract nr A026.

Языковые навыки детей с тяжелыми и множественными нарушениями развития, включающими расстройства аутистического спектра: теоретический обзор

The review paper aims to summarize the results of research on the language skills of children with autism spectrum disorders (ASD) and children with varying degrees of mental retardation (as independent, not interrelated groups) conducted by Russian and foreign scientists. The review analyzes scientific sources devoted to identifying problems in speech production and speech comprehension by children with ASD, non-linguistic factors affecting the language abilities of children with ASD, determining the relationship of language disorders and speech development disorders in children with ASD and also pays special attention to the study of oral speech of children with severe and multiple developmental disorders (with mental retardation of varying degrees). Scientific novelty lies in the fact that the conducted summarization of research findings will offer an opportunity to develop a basis for the formation of scientifically valid diagnostic tools to evaluate language skills in children with severe and multiple developmental disorders including ASD and to identify the most important criteria that can serve as indicators in the practical activities of a speech therapist. As a result, it has been substantiated that by determining the profile of language skills formation among the group of children under consideration with the help of the linguistic diagnostics of all linguistic levels, it will be possible to select the most appropriate alternative and additional means of communication for such children.

Stochastic phenotypes in RAS-dependent developmental diseases

Germline mutations upregulating RAS signaling are associated with multiple developmental disorders. A hallmark of these conditions is that the same mutation may present vastly different phenotypes in different individuals, even in monozygotic twins. Here, we demonstrate how the origins of such largely unexplained phenotypic variations may be dissected using highly controlled studies in Drosophila that have been gene edited to carry activating variants of MEK, a core enzyme in the RAS pathway. This allowed us to measure the small but consistent increase in signaling output of such alleles invivo. The fraction of mutation carriers reaching adulthood was strongly reduced, but most surviving animals had normal RAS-dependent structures. We rationalize these results using a stochastic signaling model and support it by quantifying cell fate specification errors in bilaterally symmetric larval trachea, a RAS-dependent structure that allows us to isolate the effects of mutations from potential contributions of genetic modifiers and environmental differences. We propose that the small increase in signaling output shifts the distribution of phenotypes into a regime, where stochastic variation causes defects in some individuals, but not in others. Our findings shed light on phenotypic heterogeneity of developmental disorders caused by deregulated RAS signaling and offer a framework for investigating causal effects of other pathogenic alleles and mild mutations in general.

STRESS CONDITIONS OF PRESCHOOL CHILDREN WITH MENTAL DISORDER

The article deals with the problem of stressful conditions of preschool children with mental retardation, having emotional, physical, social, intellectual, linguistic and other health characteristics, as well as their social adaptation to society, which is currently extremely relevant. The corresponding pedagogical conditions for the development of certain mental processes and qualities that are very difficult to form at later age stages are analyzed. The practical experience of educating preschool children, which require special methodological approaches and the creation of a whole range of additional conditions, is summarized. Therefore, this article discusses the stressful conditions of preschool children with mental retardation and the principles of development of young children. Particular attention is paid to the modern life of preschool children who are constantly faced with stress. The article is devoted to the peculiarities of psychological and pedagogical assistance to preschool children with mental retardation. As a result of the study, the experience of developing and implementing an early intervention program for children with multiple developmental disorders is recommended.

Creating conditions for the sustainability of communicative competencies

The study is devoted to the psychological and pedagogical problems of the formation and stability of communicative competence necessary for the effective development of children with special educational needs, including severe multiple developmental disorders, the structure and features of the state of communicative competence are considered, the features leading to the inferiority of this competence are identified: the lack of formation of speech activity and its components that participate in communicative interaction between people, difficulties in determining the potential of communication skills in children with severe multiple disabilities, difficulties in determining the uniqueness of the personal and communicative development of children of the studied category at different stages of education, as well as conditions for the formation and stability of this phenomenon in children with severe multiple developmental disabilities receiving education in preschool and school periods. Among the main conditions for the stability of this phenomenon are the definition of an algorithm for the formation of communication skills in different types of activities; the presence of team communicative interaction of all subjects of the educational process. The continuity of the accompanying process is substantiated as the basis for the formation and further stable result of communicative competence in children with severe multiple developmental disorders.

Особенности сенсомоторных и перцептивных процессов у детей младшего школьного возраста с тяжелыми множественными нарушениями развития

The article focuses on sensorimotor and perceptual processes in primary school children with multiple developmental disorders. The study involved 40 children aged 9–11 with multiple developmental issues. All the participants studied at the Secondary School of Psychological and Pedagogical Support No. 101 (Kemerovo, Russia). The experiment relied on the method developed by N. I. Ozeretskiy and M. O. Gurevich as the main diagnostic tool. The method combines a set of diagnostic tasks aimed at measuring the level of motor and perceptual development in children. The experimental study also included elements of the neuropsychological approach. The authors designed and conducted a series of practice sessions on the development of sensorimotor and perceptual processes. The neuropsychological exercises developed purposeful voluntary actions with objects and materials, improved available sensory experience, increased visual-motor coordination, sharpened the ability to navigate in various physical environments, and improved body control. They facilitated the compensation of residual reflexes, as well as the development of speech and general motor rhythmization. The exercises involved orthopedic mats, massage balls, tasks on visual-motor perception and integration, Balametrics cerebellar stimulation, etc. Statistic results showed a positive trend in the sensorimotor and perceptual processes, except for complex forms of space and time perception.

A-137 Cortical Vision Impairment: A Case Study of Associated Neurodevelopmental Disorders and Neuropsychological Findings

Abstract Objective: Cortical Visual Impairment (CVI) is characterized by a decreased visual response, related to a neurological lesion. It is the most common cause of permanent visual impairment in children. CVI is not attributed to the functioning of the eyes, but instead to visual processing centers and pathways. Deficits due to CVI may lead to impairment in cognitive, learning, and social domains. The objective of the case study is to examine neuropsychological findings of a child with CVI. Method: The subject was a 10-year, 2-month old male with a history of seizure activity. Based on decreased corpus callosum and PVL, a diagnosis of CVI was made. He evidenced significant visual latencies and difficulties with visual novelty. Continuing behavioral and academic concerns resulted in a referral for evaluation. Results: Assessment revealed extremely low cognitive ability. Relative strengths were evident in nonverbal skills. Academic skills fell at the pre-K to early K level. Neurocognitive functions ranged from the low to the very-low range with relative strengths in rapid naming, symbol recognition, semantic memory, and social intent. Findings on the SRS-2 and the ADOS-2 revealed difficulties with social awareness and communication but were not consistent with an ASD. Conclusions: CVI is a prevalent cause of visual impairment in children. Children often display multiple developmental disorders and features of autism and low cognitive ability are not uncommon. Disentangling the role of CVI in early cognitive, social, and adaptive development remains an important area for research. Assessment to identify strengths and weakness to facilitate social, academic and adaptive development is necessary.

Missense Variants Reveal Functional Insights Into the Human ARID Family of Gene Regulators

Missense variants are alterations to protein coding sequences that result in amino acid substitutions. They can be deleterious if the amino acid is required for maintaining structure or/and function, but are likely to be tolerated at other sites. Consequently, missense variation within a healthy population can mirror the effects of negative selection on protein structure and function, such that functional sites on proteins are often depleted of missense variants. Advances in high-throughput sequencing have dramatically increased the sample size of available human variation data, allowing for population-wide analysis of selective pressures. In this study, we developed a convenient set of tools, called 1D-to-3D, for visualizing the positions of missense variants on protein sequences and structures. We used these tools to characterize human homologues of the ARID family of gene regulators. ARID family members are implicated in multiple cancer types, developmental disorders, and immunological diseases but current understanding of their mechanistic roles is incomplete. Combined with phylogenetic and structural analyses, our approach allowed us to characterise sites important for protein-protein interactions, histone modification recognition, and DNA binding by the ARID proteins. We find that comparing missense depletion patterns among paralogs can reveal sub-functionalization at the level of domains. We propose that visualizing missense variants and their depletion on structures can serve as a valuable tool for complementing evolutionary and experimental findings.

Professional readiness of educational professionals for individualised psychological and pedagogical support of children with severe and multiple developmental disorders

Introduction. The current trends in modern education dictate the need for transformation and reconfiguration of the entire educational network; the changes are also reflected in updating the content for training specialists working in the system of special (remedial, correctional) and inclusive education. In this regard, the society and the state impose certain requirements on such specialists; one of them is continuous improvement of professional competencies, including practical knowledge of fundamentally new, individualised and individually differentiated technologies and practices of psychological and pedagogical support of children having severe and multiple developmental disorders. Purpose of the study: to identify the level of professional preparedness of specialists working in the system of remedial and inclusive education towards individualisation of psychological and pedagogical support for children with significant developmental disabilities. Research methodology and techniques. The research involved 64 specialists (special education teachers and special education psychologists from educational organisations of Chelyabinsk and Chelyabinsk region of the Russian Federation). The developed methodology included seven blocks in accordance with the professional activity goals and was aimed at identifying the level of formation of theoretical knowledge and the respondents’ readiness to practical activity along seven components: communicative, cognitive, planning, technological, methodological, perceptual, personal. PRI is the index of professional readiness to implement individual psychological and pedagogical support of preschool children with severe developmental disorders. Results. As a result of the experimental work, the respondents showed a medium level of readiness for individualisation of psychological and pedagogical support of children having serious developmental disorders (PRI=52.0%). The obtained data revealed a regularity manifested in the respondents’ orientation towards theoretical aspects of different professional activity tasks versus readiness for their practical realisation (the mean PRIt exceeds PRIp by 18.6%). Conclusions. The research results evidence the need for optimisation of the content and organisational forms of professional development for teachers realising the basic education programmes adapted for children with disabilities, due to the specialists’ insufficient preparedness to properly solve a number of professional activity tasks connected with individualisation of psychological and pedagogical support of children having severe and multiple developmental disabilities.

Problems of self-image creation in the aspect of the spatial image of “I” in younger school children with severe and multiple developmental disorders: theoretical and methodological substantiation

Problems of self-image creation in the aspect of the spatial image of “I” in younger school children with severe and multiple developmental disorders: theoretical and methodological substantiation

Practical aspects of the use of bodilytactile communication in remedial and developmental support of children with motor disorders in the structure of severe and multiple developmental disorders (SMDD)

Practical aspects of the use of bodilytactile communication in remedial and developmental support of children with motor disorders in the structure of severe and multiple developmental disorders (SMDD)

The use of means of alternative and additional communication in the psychological and pedagogical support of children and adolescents with severe and multiple developmental disorders as well as behavioral disorders in stationary social service institutions

The use of means of alternative and additional communication in the psychological and pedagogical support of children and adolescents with severe and multiple developmental disorders as well as behavioral disorders in stationary social service institutions

Professional preparation of students to work with children with multiple developmental disorders

Professional preparation of students to work with children with multiple developmental disorders

Features of pedagogical diagnostics of preschool children with severe and multiple developmental disorders

Features of pedagogical diagnostics of preschool children with severe and multiple developmental disorders

Влияние использования альтернативной и дополнительной коммуникации на смягчение поведенческих трудностей детей и подростков с тяжелыми множественными нарушениями развития

This article is relevant in the framework of the study educational training importance and the ability to communicate with adolescents with severe multiple developmental and behavioral disorders (SMDD) in adults working for inpa- tient social service institution (ISSI). The survey of communication and behavioral skills in adolescents with SMDD living in ISSI presented. The study involved 60 employees, 28 adolescents with SMDD, 20 parents of special children. Methods used: Communication Matrix, cyclogram «Review of the day», evaluation sheet «Table of interests». A spe- cific case of employee training and introduction of Augmentative and Alternative Communication techniques into an individual form of work with the student and the impact of these activities on improving her behavior demonstrated. The experimental data presented in this article can be used for work with ISSI to increase the communication skills available to students with SMDD. Also, the article includes the description of the work on improvement of the qual- ity of life of adolescents with SMDD that are in inpatient institutional care. It has been established that children and adolescents with SMDD living in the ISSI have persistent impairments in mastering skills, identifying their com- munication mechanisms.

Формирование стереотипа учебного поведения у детей с тяжелыми множественными нарушениями развития на занятии «Круг»

<p style="text-align: justify;">We present the development of the learning behavior patterns in children with autism spectrum disorders (ASD) with severe multiple developmental disorders (SMDD) on the model of a number of individual behavioral patterns of which the group activity “Circle” consists. The “Circle” is one of the most important organizational activities in the classroom. The study involves a class consisting of five children with severe and multiple developmental disabilities (SMDD) enrolled in the special school education program for children with ASD (so-called adopted general education program type 8.4). Present article covers the issues of the structure of the stereotype of the learning behavior, the aims of the planning psycho-educational work. As a result of the training, all children showed positive dynamics. Also, concomitant positive changes were noted associated with adaptation to schooling. After additional evidence-based studies, it is possible to transfer the practice to work with children with other developmental disorders.</p>

Личностная саморегуляция у младших школьников с ограниченными возможностями здоровья как условие их социально-психологической адаптации

Introduction. Personal self-regulation is a precondition for successful activity and social adaptation of a child. Self-regulation is directly involved in the learning process which is the leading activity of a child in the primary school age. The development of personal self-regulation is of particular importance when it comes to children with disabilities. Object of research: primary school students with disabilities. Subject of research: personal self-regulation in primary school students with disabilities as a condition for their socio-psychological adaptation. Techniques used: 1) The method for assessing self-regulation “Sticks-Dashes” (U. V. Ulyenkova); 2) The method for assessing volitional qualities based on observation (A. I. Vysotsky); 3) The questionnaire of social and psychological adaptation of personality (K. Rogers, R. Diamond). Research results: 1) A primary school student who has a physical disability but only minor mental impairments showed a higher level of self-regulation than children who, in addition to a physical disability, have additional severe multiple developmental disorders (mental retardation). 2) Children with minor mental impairments mainly have difficulties with self-regulation when placed in a new unusual environment. Children with a concomitant diagnosis have difficulties with self-regulation even in a familiar environment. 3) Younger schoolchildren with disabilities, regardless of any accompanying complications, have difficulties with socio-psychological adaptation. The level of severity of such difficulties is heterogeneous across the group under study. Conclusion. The results of our study show the need for additional psycho-correctional work with primary school students with disabilities. This work should be aimed at developing self-control skills and increasing socio-psychological adaptation. As part of a further study, it is planned to draw up an individual program for each child.