scholarly journals Neuropsychiatric Functioning in CDLS: A Detailed Phenotype and Genotype Correlation

2021 ◽  
Author(s):  
Paola Francesca Ajmone ◽  
Beatrice Allegri ◽  
Anna Cereda ◽  
Giovanni Michelini ◽  
Francesca Dall'Ara ◽  
...  
Keyword(s):  
Clinical Diagnosis ◽  
Motor Skills ◽  
Receptive Language ◽  
Autism Spectrum ◽  
Adaptive Behaviour ◽  
Intellectual Quotient ◽  
Management Interventions ◽  
Truncating Mutation ◽  
Diagnosis Group ◽  
Behavioural Aspects

Abstract Background: Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder and its phenotype clinical expression is widely variable. Despite the growing interest on genotype-phenotype correlations and on behaviour phenotype of genetic syndromes, specific studies in CdLS cohorts evaluating the correlations between genotype and neurodevelopmental characteristics, Behaviour and communicative aspects are limited, most of these studies are descriptive and there is a lack of specific assessment protocols.Methods: Neurodevelopmental and Behavioural phenotype of all the patients (N = 38) was assessed using a specific neuropsychiatric protocol, concerning Intellectual Quotient (IQ), General Quotient of Development (GQ), communicative skills, behavioural aspects and adaptive behaviour based on direct and indirect evaluation. Subsequently, we searched for possible genotype–phenotype correlations comparing individuals with NIPBL variants (CdLS NIPBL mutated group) and patients with negative molecular results (CdLS clinical diagnosis group). Results: The first part of the study showed a higher percentage of subjects with normal Intellectual Quotient (IQ) and Borderline Intellectual Functioning if compared with previous data; adaptive skills were lower than expected for age in all participants and the weakest areas were Socialization, Motor Skills, and Communication. Expressive language was more compromised than receptive language, nevertheless receptive abilities were also impaired. 39.5% of the sample presented with Autism Spectrum Disorder (ASD). By stratifying CdLS phenotypes by genetic, NIPBL mutated individuals demonstrated a worse trend in cognitive functioning, in communication expressive skills, in motor skills and in ASD symptoms in comparison with the Clinical Diagnosis Group. Individuals with non-Truncating mutation (mostly missense) displayed better abilities in Communication and in relational aspects with no ASD while Truncating individuals presented with worse abilities in Daily Living Skills, Socialization, Motor Skills, and Communicative abilities. Conclusions: These findings should increase our awareness of the strengths and weaknesses points in CdLS individuals to guide appropriate targeted management; interventions addressing communicative impairments represent a clinical priority in CdLS patients.

scholarly journals Decreased Mitogen Inducible Gene 6 (MIG-6) Associated with Symptom Severity in Children with Autism

2014 ◽  
Vol 9 ◽  
pp. BMI.S15218 ◽  
Author(s):  
AJ Russo
Keyword(s):  
Growth Factor ◽  
Motor Skills ◽  
Symptom Severity ◽  
Receptive Language ◽  
Autism Spectrum ◽  
Tnf Alpha ◽  
Autistic Children ◽  
Epidermal Growth ◽  
Spectrum Disorders ◽  
Inducible Gene

Background Individuals with autism spectrum disorders (ASDs) demonstrate impairment in social interactions and problems in verbal and nonverbal communication. Autism spectrum disorders are thought to affect 1 in 88 children in the US. Recent research has shown that epidermal growth factor receptor (EGFR) activation is associated with nerve cell development and repair. Mitogen inducible gene 6 (MIG-6) is a 58-kDa non-kinase scaffolding adaptor protein consisting of 462 amino-acids, which has been shown to be a negative feedback regulator of EGFR and Met receptor tyrosine kinase (RTK) signaling. Subjects and Methods In this study, we determined plasma levels of MIG-6, which suppresses the EGFR RTK pathway in autistic children, and compared MIG-6 levels with the EGFR ligand, epidermal growth factor (EGF), and the cMET ligand, hepatocyte growth factor (HGF). MIG-6 levels were also compared to the symptom severity of 19 different autistic behaviors. Plasma MIG-6 concentration was measured in 40 autistic children and 39 neurotypical, age, and gender similar controls using an enzyme linked immunosorbent assay (ELISA). Plasma MIG-6 levels were compared to putative biomarkers known to be associated with EGFR and cMET and severity levels of 19 autism related symptoms [awareness, expressive language, receptive language, (conversational) pragmatic language, focus/attention, hyperactivity, impulsivity, perseveration, fine motor skills, gross motor skills, hypotonia (low muscle tone), tip toeing, rocking/pacing, stimming, obsessions/fixations, eye contact, sound sensitivity, light sensitivity, and tactile sensitivity]. Results In this study, we found that plasma MIG-6 levels in autistic children (182.41 ±24.3 pg/ml) were significantly lower than neurotypical controls (1779.76 ± 352.5; P = 1.76E − 5). Decreased MIG-6 levels correlated with serotonin, dopamine, Tumor necrosis factor alpha (TNF-alpha), and urokinase receptor (uPAR) concentration, but not with other tested putative biomarkers. MIG-6 levels also correlated significantly with severity of expressive language, receptive language, tip toeing, rocking/pacing, and hand flapping/stimming. Conclusions These results suggest a relationship between decreased plasma MIG-6 levels, biomarkers associated with the EGFR pathway, and symptom severity in autism. A strong correlation between plasma MIG-6 and dopamine and serotonin levels suggest that decreased MIG-6 levels may be associated with abnormal neurotransmitter synthesis and/or action. A strong correlation between MIG-6 and uPAR and the inflammatory marker TNF-alpha suggests that low MIG-6 levels may be associated with the HGF/Met signaling pathway, as well as inflammation in autistic children.

scholarly journals Decreased Epidermal Growth Factor (EGF) Associated with HMGB1 and Increased Hyperactivity in Children with Autism

2013 ◽  
Vol 8 ◽  
pp. BMI.S11270 ◽  
Author(s):  
Anthony J. Russo
Keyword(s):  
Growth Factor ◽  
Motor Skills ◽  
Symptom Severity ◽  
The United States ◽  
Receptive Language ◽  
Autism Spectrum ◽  
Fine Motor ◽  
Autistic Children ◽  
Gross Motor ◽  
Gross Motor Skills

Background Autism spectrum disorders (ASDs), characterized by impaired social interactions and deficits in verbal and nonverbal communication, are thought to affect 1 in 88 children in the United States. There is much support for the role of growth factors in the etiology of autism. Recent research has shown that epithelial growth factor (EGF) is decreased in young autistic children (2–4 years of age). This study was designed to determine plasma levels of EGF in an older group of autistic children (mean age 10.6 years) and to correlate these EGF levels with putative biomarkers HGF, uPA, uPAR, GAD2, MPO GABA, and HMGB1, as well as symptom severity of 19 different symptoms. Subjects and Methods Plasma from 38 autistic children, 11 children with pervasive developmental disorder (PDD-NOS) and 40 neurotypical, age and gender similar controls was assessed for EGF concentration using ELISAs. Severity of 19 symptoms (awareness, expressive language, receptive language, (conversational) pragmatic language, focus/attention, hyperactivity, impulsivity, perseveration, fine motor skills, gross motor skills, hypotonia (low muscle tone), tiptoeing, rocking/pacing, stimming, obsessions/fixations, eye contact, sound sensitivity, light sensitivity, and tactile sensitivity) was assessed and then compared to EGF concentrations. Results In this study, we found EGF levels in autistic children and those with PDD-NOS to be significantly lower when compared with neurotypical controls. EGF levels correlated with HMGB1 levels but not the other tested putative biomarkers, and EGF correlated negatively with hyperactivity, gross motor skills, and tiptoeing but not other symptoms. Conclusions These results suggest an association between decreased plasma EGF levels and selected symptom severity. We also found a strong correlation between plasma EGF and HMGB1, suggesting inflammation is associated with decreased EGF.

Relationship between Motor Skills and Language Abilities in Children with Autism Spectrum Disorder

2021 ◽  
Author(s):  
Yen-Tzu Wu ◽  
Chih-Hsuan Tsao ◽  
Hsiao-Ching Huang ◽  
Tian-Ai Yang ◽  
Yao-Jen Li
Keyword(s):  
Autism Spectrum Disorder ◽  
Motor Skills ◽  
Expressive Language ◽  
Receptive Language ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Language Abilities ◽  
Motor Functioning ◽  
Peabody Developmental Motor Scales ◽  
The Relationship

Abstract Objectives Few studies have examined the relationship between language abilities and specific motor skills in toddlers with autism spectrum disorder (ASD). The aim of this study was to compare the relationship of receptive language (RL) and expressive language (EL) abilities with motor functioning between toddlers with ASD aged 24–36 months and their typically developing (TD) peers. Furthermore, the study compared multidimensional motor functioning between toddlers with ASD with delayed RL and EL development and toddlers with ASD and typical RL and EL development. The predictive powers of the motor skills were examined for the group with delayed RL and EL development. Methods The language abilities of 38 toddlers with ASD and 38 age-matched TD toddlers were evaluated using the Receptive and Expressive Language Subscales of the Mullen Scale of Early Learning, and their motor skills were assessed using the Peabody Developmental Motor Scales, 2nd Edition. Results Significant correlations between language ability and motor functioning were observed in the ASD and TD groups. The ASD group with delayed RL and EL development had lower scores for multidimensional motor functioning than the ASD group with typical RL and EL development and the TD group. Moreover, the risks of delayed EL and RL development could be predicted by the lower motor scores among toddlers with ASD. Conclusions The positive correlation between language abilities and motor functioning among toddlers with ASD indicated potential connections between the early onsets of motor and speech–language impairments among these toddlers. Impact The results may have implications for the development of motor-based interventions targeting language development among young children with ASD.

Gender differences in the developmental outcomes of children with congenital cardiac defects

2012 ◽  
Vol 22 (5) ◽  
pp. 514-519 ◽  
Author(s):  
Annette Majnemer ◽  
Catherine Limperopoulos ◽  
Michael Shevell ◽  
Charles Rohlicek ◽  
Bernard Rosenblatt ◽  
...  
Keyword(s):  
Gender Differences ◽  
Brain Injury ◽  
Functional Independence Measure ◽  
Early Brain Injury ◽  
Functional Independence ◽  
Receptive Language ◽  
Full Scale ◽  
Fine Motor ◽  
Intellectual Quotient ◽  
Neuroprotective Strategies

AbstractObjectiveThis study compares the developmental and functional outcomes at school entry between boys and girls born with a congenital cardiac defect who required early surgical correction.Study designA prospective cohort of 94 children, including 49 percent boys, were followed up to 5 years of age and assessed for developmental progress. Developmental measures included Wechsler Preschool and Primary Scale of Intelligence – cognitive; Peabody Picture Vocabulary Test – receptive language; Peabody Developmental Motor Scale – motor; and Child Behaviour Checklist – behaviour. Measures of function included the Vineland Adaptive Behavior Scale and Functional Independence Measure for Children (WeeFIM).ResultsThe mean scores of the boys on the WeeFIM subscales, such as self-care, mobility, cognition, were significantly lower than that of the girls. There was a trend for a greater proportion of boys to have abnormalities on neurological examination (boys 37.5 percent abnormal, girls 19.5 percent abnormal). Verbal, performance, and full scale Intellectual Quotients were 5–7 points lower in boys but did not reach significance (full scale Intellectual Quotient: boys 87.7 plus or minus 22.2; girls 93.9 plus or minus 19.3). Boys were more likely to have fine motor delays (50 percent, 82.7 plus or minus 16.5) compared with girls (28.2 percent, 87.0 plus or minus 15.8). There were no gender differences in receptive language or behavioural difficulties.ConclusionsBoys born with congenital heart disease requiring early surgical repair appear to be at enhanced risk for neuromotor impairments and activity limitations. Findings support gender differences in the pathogenesis of early brain injury following hypoxic–ischaemic insults. This has implications for neuroprotective strategies to prevent brain injury.

scholarly journals SENP1 in the retrosplenial agranular cortex regulates core autistic-like symptoms in mice

2021 ◽  
Author(s):  
Kan Yang ◽  
Yuhan Shi ◽  
Xiujuan Du ◽  
Yuefang Zhang ◽  
Shifang Shan ◽  
...  
Keyword(s):  
Social Interaction ◽  
De Novo ◽  
Fragile X ◽  
Neurodevelopmental Disorder ◽  
Autism Spectrum ◽  
Repetitive Behaviors ◽  
Genetic Components ◽  
Truncating Mutation ◽  
Synaptic Functions ◽  
Core Symptoms

AbstractAutism spectrum disorder (ASD) is a highly heritable complex neurodevelopmental disorder. While the core symptoms of ASD are defects of social interaction and repetitive behaviors, over 50% of ASD patients have comorbidity of intellectual disabilities (ID) or developmental delay (DD), raising the question whether there are genetic components and neural circuits specific for core symptoms of ASD. Here, by focusing on ASD patients who do not show compound ID or DD, we identified a de novo heterozygous gene-truncating mutation of the Sentrin-specific peptidase1 (SENP1) gene, coding the small ubiquitin-like modifiers (SUMO) deconjugating enzyme, as a potentially new candidate gene for ASD. We found that Senp1 haploinsufficient mice exhibited core symptoms of autism such as deficits in social interaction and repetitive behaviors, but normal learning and memory ability. Moreover, we found that the inhibitory and excitatory synaptic functions were severely affected in the retrosplenial agranular (RSA) cortex of Senp1 haploinsufficient mice. Lack of Senp1 led to over SUMOylation and degradation of fragile X mental retardation protein (FMRP) proteins, which is coded by the FMR1 gene, also implicated in syndromic autism. Importantly, re-introducing SENP1 or FMRP specifically in RSA fully rescued the defects of synaptic functions and core autistic-like symptoms of Senp1 haploinsufficient mice. Taken together, these results elucidate that disruption of the SENP1-FMRP regulatory axis in the RSA may cause core autistic symptoms, which further provide a candidate brain region for therapeutic intervene of ASD by neural modulation approaches.

scholarly journals AYURVEDIC MANAGEMENT OF DUCHENNE MUSCULAR DYSTROPHY: A SHORT REVIEW

2019 ◽  
Vol 7 (1) ◽  
pp. 179-183
Author(s):  
Akshay A Patankar ◽  
Renu B Rathi
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Social Contact ◽  
Signs And Symptoms ◽  
Short Review ◽  
Receptive Language ◽  
Modern Medicine ◽  
Autism Spectrum ◽  
Neuromuscular Disorder ◽  
Significant Treatment

Duchenne muscular dystrophy is a neuromuscular disorder characterized by deficient dystrophin protein in the muscle. The main symptoms the patient presented were delay in expressive and receptive language development, visual discontent, hyperkinetic behaviour, and inability to initiate and maintain social contact with peers. The data obtained from the family, following clinical examination, laboratory investigation results and assessment of mental status were significant for the diagnosis of Autism Spectrum Disorder, hyperkinetic behaviour and Duchenne Muscular Dystrophy. In Ayurveda it has been classified under Medomamsa dusti further vitiates the Vata doshas occurs due to the Bheejabagahaavyava Dusti. In modern medicine there is no significant treatment available for this diseases while in Ayurvedic panchakrma therapy shows significant results in all signs and symptoms of this diseases.

scholarly journals Receptive Language in Primary-School-Aged Children with Autism Spectrum Disorder.

2021 ◽  
Vol 10 (4) ◽  
pp. 137-161
Author(s):  
D.S. Pereverzeva ◽  
U.A. Mamokhina ◽  
E.Yu. Davydova ◽  
A.A. Lopukhina ◽  
V.G. Arutiunian ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Autistic Traits ◽  
Children With Autism ◽  
Receptive Language ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Verbal Intelligence ◽  
School Aged Children ◽  
Autistic Disorders ◽  
The Relationship

The objective of the present study is to investigate the relationship between the receptive language, and the index of non-verbal intelligence and the level of severity of autistic disorders in primary-school-aged children with Autism spectrum disorder. One of the main areas influenced by autistic disorders is communication. Therefore, the study of the language abilities of such children and factors that affect them provides a better approach to the therapy and education. The sample included 50 children aged 7–11 years diagnosed with autism spectrum disorders. Children were tested using the KORABLIK method (basic linguistic skills), the Kaufman Assessment Battery for Children (KABC-II) or the Wechsler Intelligence Scale for Children ― Third Edition (WISC-III) (non-verbal intelligence), the Autism Diagnosis Observation Schedule ― Second Edition (ADOS-II) (autistic traits). The results support the hypothesis of the relationship between receptive language skills, the index of non-verbal intelligence, and symptoms of autism. The severity of autistic traits is negatively associated with some phonological and lexical levels of the receptive speech, as well as with understanding of discourse. The non-verbal intelligence index is positively associated with speech comprehension at all levels. A specific feature of receptive language in children with Autism spectrum disorder aged 7–11 years is the uneven development, which is associated with the severity of autistic traits and is not associated with the intelligence level.

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