scholarly journals Molecular and phenotypic characteristics of 15q24 microdeletion in pediatric patients with developmental disorders

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yuanyuan Zhang ◽  
Xiaoliang Liu ◽  
Haiming Gao ◽  
Wanting Cui ◽  
Bijun Zhang ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
Genetic Disorder ◽  
Daily Practice ◽  
Homozygous Deletion ◽  
Autism Spectrum ◽  
Clinical Findings ◽  
Lower Limbs ◽  
Facial Dysmorphism ◽  
Microdeletion Syndrome ◽  
Cytochrome P450 Family

AbstractChromosome 15q24 microdeletion is a rare genetic disorder characterized by development delay, facial dysmorphism, congenital malformations, and occasional autism spectrum disorder (ASD). In this study, we identified five cases of 15q24 microdeletion using multiplex ligation-dependent probe amplification (MLPA) technology in a cohort of patients with developmental delay and/or intellectual disability. Two of these five cases had deletions that overlapped with the previously defined 1.1 Mb region observed in most reported cases. Two cases had smaller deletions (< 0.57 Mb) in the 15q24.1 low copy repeat (LCR) B-C region. They presented significant neurobehavioral features, suggesting that this smaller interval is critical for core phenotypes of 15q24 microdeletion syndrome. One case had minimal homozygous deletion of less than 0.11 Mb in the 15q24.1 LCR B-C region, which contained CYP1A1 (cytochrome P450 family 1 subfamily A member 1) and EDC3 (enhancer of mRNA decapping 3) genes, resulting in poor immunity, severe laryngeal stridor, and lower limbs swelling. This study provides additional evidence of 15q24 microdeletion syndrome with genetic and clinical findings. The results will be of significance to pediatricians in their daily practice.

scholarly journals Cornelia de Lange Syndrome and Psychiatric’s Assistance

2020 ◽  
Vol 9 (2) ◽  
pp. 30
Author(s):  
Katharina Merry Apriliani ◽  
Yunias Setiawati
Keyword(s):  
Developmental Disorders ◽  
Sleep Problems ◽  
Genetic Disorder ◽  
Autism Spectrum ◽  
Speaking Anxiety ◽  
Social Interventions ◽  
Organ Systems ◽  
Cornelia De Lange ◽  
Intellectual Level

Cornelia de Lange's syndrome (CdLS) is a genetic disorder characterized by developmental disorders in several organ systems, including the brain, bones, digestion, immunity, endocrine, and others. This syndrome is mainly caused by mutations in the NIPBL, SMC3, and SMC1A genes. CdLS are generally comorbid with developmental or intellectual-level disorders, autism spectrum disorders, self-injury behavior, difficulty speaking, anxiety, hyperactivity, and sleep problems. This CdLS has a significant impact on the quality of life and maladaptive function in patients, as well as causing psychological disorders for families. Therefore, the need for psychiatric assistance for family psychoeducation, psycho-social interventions and cognitive-behavioral education.

Comparison of standardised lymphoscintigraphic function test and high resolution sonography of the lymphoedema of legs

Phlebologie ◽  
2008 ◽  
Vol 37 (05) ◽  
pp. 247-252 ◽  
Author(s):  
V. S. Brauer ◽  
W. J. Brauer
Keyword(s):  
Lower Leg ◽  
Clinical Findings ◽  
Lower Limbs ◽  
Fatty Tissue ◽  
Qualitative And Quantitative ◽  
Function Test ◽  
Unreliable Method ◽  
Negative Conclusion ◽  
Fine Disperse

SummaryPurpose: Comparison of qualitative and quantitative sonography with the lymphoscintigraphic function test and clinical findings in legs. Patients, methods: In 33 patients a lymphoscintigraphic function test of legs combined with measurement of lymph node uptake was performed and subsequently compared with sonography. Sonographic criteria were: Thickness of cutis, thickness of subcutanean fatty tissue and presence of liquid structures or fine disperse tissue structure of lower limbs, foots and toes. Results: In 51 legs uptake values lie in the pathologic area, in four legs in the grey area and in ten legs in the normal area. The cutis thickness in the lower leg shows no significant correlation with the uptake. The determination of the thickness of the subcutanean fatty tissue of the lower leg and of the cutis thickness of the feet turned out to be an unreliable method. In 47% of the medial lower legs and in 57% of the lateral lower legs with clinical lymphoedema sonography is falsely negative. Conclusion: Early lymphoedema is only detectable with the lymphoscintigraphic function test. In the case of clinical lymphoedema clinical examination is more reliable than sonography.

Hearing and Neurodevelopmental Outcomes of Young Infants with Parechovirus-A and Enterovirus Meningitis: Cohort Study in Singapore Children and Literature Review

2020 ◽  
Author(s):  
Elis Yuexian Lee ◽  
Jessica Hui Yin Tan ◽  
Chew Thye Choong ◽  
Nancy Wen Sim Tee ◽  
Chia Yin Chong ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Oropharyngeal Dysphagia ◽  
Significant Risk ◽  
Developmental Outcomes ◽  
Autism Spectrum ◽  
Clinical Findings ◽  
Cortical Blindness ◽  
Speech Delay ◽  
Neurodevelopmental Outcomes ◽  
Young Infants

Abstract Parechovirus-A (PeV-A) and Enterovirus (EV) commonly cause childhood aseptic meningitis. Bacterial meningitis in children has been associated with devastating long-term sequelae. However, developmental outcomes are unclear in Parechovirus meningitis. This study aims to review the clinical findings and developmental outcomes of infants with PeV-A and EV meningitis. We performed a retrospective study of infants aged 90 days or younger being admitted to our hospital with PeV-A meningitis between November 2015 and July 2017, with positive cerebrospinal fluid (CSF) PeV-A PCR and negative blood and CSF bacterial cultures. Hearing and neurodevelopmental outcomes were compared with a previous cohort of infants aged 90 days or younger with EV meningitis admitted from January 2015 to December 2015. A total of 161 infants were included in our study, of which 68 infants (42.2%) had PeV-A meningitis and 93 infants (57.8%) had EV meningitis. We assessed their developmental outcome at 6 months, 1 year, and 2 years post-meningitis. At 2 years post-meningitis, three infants with PeV-A meningitis had developmental delay (5.5%), whereas none with EV meningitis had developmental delay. One patient had speech delay and autism spectrum disorder, while two had mild speech delay. When compared with our cohort of EV meningitis ≤90 days old, children with PeV-A meningitis ≤90 days old were more likely to have developmental delay 2 years post-meningitis (odds ratio 2.4, 95% confidence interval 2.0–3.0, p = 0.043). None of the patients with PeV-A or EV meningitis had sensorineural hearing loss or neurological sequelae, such as cortical blindness, oropharyngeal dysphagia, hydrocephalus, epilepsy, or cerebral palsy. Infants with PeV-A meningitis had a significant risk of developmental delay 2 years post-meningitis compared with those with EV meningitis. It is important to follow-up the developmental milestones of infants diagnosed with PeV-A meningitis for at least 2 years; and when they develop developmental delay, to ensure that they receive appropriate intervention.

scholarly journals Chromatin Remodeler CHD8 in Autism and Brain Development

2021 ◽  
Vol 10 (2) ◽  
pp. 366
Author(s):  
Anke Hoffmann ◽  
Dietmar Spengler
Keyword(s):  
Animal Studies ◽  
Mental Disease ◽  
Transgenic Animal ◽  
Autism Spectrum ◽  
Homeostatic Plasticity ◽  
Therapeutic Interventions ◽  
Model Organisms ◽  
Facial Dysmorphism ◽  
Transcriptional Level ◽  
Level Function

Chromodomain Helicase DNA-binding 8 (CHD8) is a high confidence risk factor for autism spectrum disorders (ASDs) and the genetic cause of a distinct neurodevelopmental syndrome with the core symptoms of autism, macrocephaly, and facial dysmorphism. The role of CHD8 is well-characterized at the structural, biochemical, and transcriptional level. By contrast, much less is understood regarding how mutations in CHD8 underpin altered brain function and mental disease. Studies on various model organisms have been proven critical to tackle this challenge. Here, we scrutinize recent advances in this field with a focus on phenotypes in transgenic animal models and highlight key findings on neurodevelopment, neuronal connectivity, neurotransmission, synaptic and homeostatic plasticity, and habituation. Against this backdrop, we further discuss how to improve future animal studies, both in terms of technical issues and with respect to the sex-specific effects of Chd8 mutations for neuronal and higher-systems level function. We also consider outstanding questions in the field including ‘humanized’ mice models, therapeutic interventions, and how the use of pluripotent stem cell-derived cerebral organoids might help to address differences in neurodevelopment trajectories between model organisms and humans.

scholarly journals Early Diagnostics and Early Intervention in Neurodevelopmental Disorders—Age-Dependent Challenges and Opportunities

2021 ◽  
Vol 10 (4) ◽  
pp. 861
Author(s):  
Mijna Hadders-Algra
Keyword(s):  
Early Intervention ◽  
High Risk ◽  
Early Detection ◽  
Developmental Disorders ◽  
Familial Risk ◽  
Brain Structures ◽  
Autism Spectrum ◽  
First Year ◽  
Early Diagnostics ◽  
Challenges And Opportunities

This review discusses early diagnostics and early intervention in developmental disorders in the light of brain development. The best instruments for early detection of cerebral palsy (CP) with or without intellectual disability are neonatal magnetic resonance imaging, general movements assessment at 2–4 months and from 2–4 months onwards, the Hammersmith Infant Neurological Examination and Standardized Infant NeuroDevelopmental Assessment. Early detection of autism spectrum disorders (ASD) is difficult; its first signs emerge at the end of the first year. Prediction with the Modified Checklist for Autism in Toddlers and Infant Toddler Checklist is possible to some extent and improves during the second year, especially in children at familial risk of ASD. Thus, prediction improves substantially when transient brain structures have been replaced by permanent circuitries. At around 3 months the cortical subplate has dissolved in primary motor and sensory cortices; around 12 months the cortical subplate in prefrontal and parieto-temporal cortices and cerebellar external granular layer have disappeared. This review stresses that families are pivotal in early intervention. It summarizes evidence on the effectiveness of early intervention in medically fragile neonates, infants at low to moderate risk, infants with or at high risk of CP and with or at high risk of ASD.

scholarly journals Health-Related Quality of Life in Children with Developmental Disorders

2021 ◽  
Author(s):  
Marina M. Schoemaker ◽  
Suzanne Houwen
Keyword(s):  
Quality Of Life ◽  
Developmental Disorders ◽  
Developmental Coordination Disorder ◽  
Autism Spectrum ◽  
Future Research ◽  
Health Related Quality ◽  
Related Quality ◽  
Health Related ◽  
Lower Hrqol

Abstract Purpose of Review (1) To give an overview of what is currently known about health-related quality of life (HRQoL) in three common and co-occurring developmental disorders: attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASD), and developmental coordination disorder (DCD), and (2) to provide directions for future research. Recent Findings HRQoL is compromised in all three developmental disorders, affecting various domains of HRQoL. However, some domains are more affected than others depending on the nature of the core deficits of the disorder. Overall, parents’ rate HRQoL of their children lower than the children themselves. Children with ASD and ADHD with co-occurring disorders have lower HRQoL compared to those with singular disorders. Future studies in DCD are needed to investigate the effect of co-occurring disorder in this population. Summary Children with developmental disorders have lower HRQoL than typically developing children. Future research should focus on the effects of co-occurring disorders on HRQoL and on protective factors that may increase HRQoL. HRQoL should be a part of clinical assessment, as it reveals the areas in life children are struggling with that could be targeted during intervention.

scholarly journals MED12-Related (Neuro)Developmental Disorders: A Question of Causality

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 663
Author(s):  
Stijn van de Plassche ◽  
Arjan PM de Brouwer
Keyword(s):  
Developmental Disorders ◽  
De Novo ◽  
Expression Patterns ◽  
Mediator Complex ◽  
Gene Expression Patterns ◽  
Facial Dysmorphism ◽  
Regulation Of Transcription ◽  
Feeding Difficulties ◽  
Missense Variants ◽  
Pathogenic Variants

MED12 is a member of the Mediator complex that is involved in the regulation of transcription. Missense variants in MED12 cause FG syndrome, Lujan-Fryns syndrome, and Ohdo syndrome, as well as non-syndromic intellectual disability (ID) in hemizygous males. Recently, female patients with de novo missense variants and de novo protein truncating variants in MED12 were described, resulting in a clinical spectrum centered around ID and Hardikar syndrome without ID. The missense variants are found throughout MED12, whether they are inherited in hemizygous males or de novo in females. They can result in syndromic or nonsyndromic ID. The de novo nonsense variants resulting in Hardikar syndrome that is characterized by facial clefting, pigmentary retinopathy, biliary anomalies, and intestinal malrotation, are found more N-terminally, whereas the more C-terminally positioned variants are de novo protein truncating variants that cause a severe, syndromic phenotype consisting of ID, facial dysmorphism, short stature, skeletal abnormalities, feeding difficulties, and variable other abnormalities. This broad range of distinct phenotypes calls for a method to distinguish between pathogenic and non-pathogenic variants in MED12. We propose an isogenic iNeuron model to establish the unique gene expression patterns that are associated with the specific MED12 variants. The discovery of these patterns would help in future diagnostics and determine the causality of the MED12 variants.

scholarly journals Mice with mutations in Trpm1, a gene in the locus of 15q13.3 microdeletion syndrome, display pronounced hyperactivity and decreased anxiety-like behavior

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tesshu Hori ◽  
Shohei Ikuta ◽  
Satoko Hattori ◽  
Keizo Takao ◽  
Tsuyoshi Miyakawa ◽  
...  
Keyword(s):  
Visual Impairment ◽  
Wide Spectrum ◽  
Genetic Disorder ◽  
Mutant Mice ◽  
Chromosome 15 ◽  
Microdeletion Syndrome ◽  
Visual Transduction ◽  
The Central Nervous System ◽  
Null Mutant Mice

AbstractThe 15q13.3 microdeletion syndrome is a genetic disorder characterized by a wide spectrum of psychiatric disorders that is caused by the deletion of a region containing 7 genes on chromosome 15 (MTMR10, FAN1, TRPM1, MIR211, KLF13, OTUD7A, and CHRNA7). The contribution of each gene in this syndrome has been studied using mutant mouse models, but no single mouse model recapitulates the whole spectrum of human 15q13.3 microdeletion syndrome. The behavior of Trpm1−/− mice has not been investigated in relation to 15q13.3 microdeletion syndrome due to the visual impairment in these mice, which may confound the results of behavioral tests involving vision. We were able to perform a comprehensive behavioral test battery using Trpm1 null mutant mice to investigate the role of Trpm1, which is thought to be expressed solely in the retina, in the central nervous system and to examine the relationship between TRPM1 and 15q13.3 microdeletion syndrome. Our data demonstrate that Trpm1−/− mice exhibit abnormal behaviors that may explain some phenotypes of 15q13.3 microdeletion syndrome, including reduced anxiety-like behavior, abnormal social interaction, attenuated fear memory, and the most prominent phenotype of Trpm1 mutant mice, hyperactivity. While the ON visual transduction pathway is impaired in Trpm1−/− mice, we did not detect compensatory high sensitivities for other sensory modalities. The pathway for visual impairment is the same between Trpm1−/− mice and mGluR6−/− mice, but hyperlocomotor activity has not been reported in mGluR6−/− mice. These data suggest that the phenotype of Trpm1−/− mice extends beyond that expected from visual impairment alone. Here, we provide the first evidence associating TRPM1 with impairment of cognitive function similar to that observed in phenotypes of 15q13.3 microdeletion syndrome.

AUTMINER: A SYSTEM FOR EXTRACTING ASD-RELATED GENES USING TEXT MINING

2011 ◽  
Vol 19 (01) ◽  
pp. 113-125 ◽  
Author(s):  
LEJUN GONG ◽  
XIAO SUN ◽  
DONGKE JIANG ◽  
SHENGTAO GONG
Keyword(s):  
Autism Spectrum Disorders ◽  
Text Mining ◽  
Genetic Screening ◽  
Gene Network ◽  
Developmental Disorders ◽  
Autism Spectrum ◽  
Major Focus ◽  
Genetic Complexity ◽  
Spectrum Disorders ◽  
Reference Tool

Autism spectrum disorders (ASD) represent a group of developmental disorders with strong genetic underpinnings. To explore the genetic complexity of ASD, we developed AutMiner (), a public web-portal for the collection of genes linked to ASD, and the implementation of an autism-centre network. AutMiner extracts candidate genes associated with ASD using text mining from 9276 abstracts. Compared to other recent systems, gene entries are richer to provide a reference for clinical geneticists. AutMiner also constructs ASD-related network consisting of autism-gene network and gene-gene network. To the best of our knowledge, this is the first web example of ASD-related network. The major focus of AutMiner is to offer a valuable reference tool for clinical geneticists in establishing and implementing effective genetic screening programmes for those patients with ASD.

scholarly journals Autism Spectrum Disorder from the Womb to Adulthood: Suggestions for a Paradigm Shift

2021 ◽  
Vol 11 (2) ◽  
pp. 70
Author(s):  
Cristina Panisi ◽  
Franca Rosa Guerini ◽  
Provvidenza Maria Abruzzo ◽  
Federico Balzola ◽  
Pier Mario Biava ◽  
...  
Keyword(s):  
Paradigm Shift ◽  
Genetic Model ◽  
Time Window ◽  
Wide Spectrum ◽  
Autism Spectrum ◽  
Clinical Findings ◽  
Theoretical Issue ◽  
Common Thread ◽  
Spectrum Disorders ◽  
Interdisciplinary Healthcare

The wide spectrum of unique needs and strengths of Autism Spectrum Disorders (ASD) is a challenge for the worldwide healthcare system. With the plethora of information from research, a common thread is required to conceptualize an exhaustive pathogenetic paradigm. The epidemiological and clinical findings in ASD cannot be explained by the traditional linear genetic model, hence the need to move towards a more fluid conception, integrating genetics, environment, and epigenetics as a whole. The embryo-fetal period and the first two years of life (the so-called ‘First 1000 Days’) are the crucial time window for neurodevelopment. In particular, the interplay and the vicious loop between immune activation, gut dysbiosis, and mitochondrial impairment/oxidative stress significantly affects neurodevelopment during pregnancy and undermines the health of ASD people throughout life. Consequently, the most effective intervention in ASD is expected by primary prevention aimed at pregnancy and at early control of the main effector molecular pathways. We will reason here on a comprehensive and exhaustive pathogenetic paradigm in ASD, viewed not just as a theoretical issue, but as a tool to provide suggestions for effective preventive strategies and personalized, dynamic (from womb to adulthood), systemic, and interdisciplinary healthcare approach.

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