scholarly journals Clinical characterization of children and adolescents with NF1 microdeletions

2020 ◽  
Vol 36 (10) ◽  
pp. 2297-2310 ◽  
Author(s):  
Hildegard Kehrer-Sawatzki ◽  
Lan Kluwe ◽  
Johannes Salamon ◽  
Lennart Well ◽  
Said Farschtschi ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Developmental Delay ◽  
Clinical Care ◽  
Severe Disease ◽  
Autism Spectrum ◽  
Whole Body ◽  
Global Developmental Delay ◽  
Disease Manifestation ◽  
Tumour Load ◽  
The Mean

Abstract Purpose An estimated 5–11% of patients with neurofibromatosis type 1 (NF1) harbour NF1 microdeletions encompassing the NF1 gene and its flanking regions. The purpose of this study was to evaluate the clinical phenotype in children and adolescents with NF1 microdeletions. Methods We retrospectively analysed 30 children and adolescents with NF1 microdeletions pertaining to externally visible neurofibromas. The internal tumour load was determined by volumetry of whole-body magnetic resonance imaging (MRI) in 20 children and adolescents with NF1 microdeletions. Furthermore, the prevalence of global developmental delay, autism spectrum disorder and attention deficit hyperactivity disorder (ADHD) were evaluated. Results Children and adolescents with NF1 microdeletions had significantly more often cutaneous, subcutaneous and externally visible plexiform neurofibromas than age-matched patients with intragenic NF1 mutations. Internal neurofibromas were detected in all 20 children and adolescents with NF1 microdeletions analysed by whole-body MRI. By contrast, only 17 (61%) of 28 age-matched NF1 patients without microdeletions had internal tumours. The total internal tumour load was significantly higher in NF1 microdeletion patients than in NF1 patients without microdeletions. Global developmental delay was observed in 28 (93%) of 30 children with NF1 microdeletions investigated. The mean full-scale intelligence quotient in our patient group was 77.7 which is significantly lower than that of patients with intragenic NF1 mutations. ADHD was diagnosed in 15 (88%) of 17 children and adolescents with NF1 microdeletion. Furthermore, 17 (71%) of the 24 patients investigated had T-scores ≥ 60 up to 75, indicative of mild to moderate autistic symptoms, which are consequently significantly more frequent in patients with NF1 microdeletions than in the general NF1 population. Also, the mean total T-score was significantly higher in patients with NF1 microdeletions than in the general NF1 population. Conclusion Our findings indicate that already at a very young age, NF1 microdeletions patients frequently exhibit a severe disease manifestation which requires specialized long-term clinical care.

Sleep Disorder: An Overlooked Manifestation of Glucose Transporter Type-1 Deficiency Syndrome

2021 ◽  
Author(s):  
Kingthong Anurat ◽  
Chaiyos Khongkhatithum ◽  
Thipwimol Tim-Aroon ◽  
Chanin Limwongse ◽  
Lunliya Thampratankul
Keyword(s):  
Sleep Disorder ◽  
Developmental Delay ◽  
Daytime Sleepiness ◽  
Glucose Transporter ◽  
Focal Epilepsy ◽  
Deficiency Syndrome ◽  
Clinical Findings ◽  
Whole Body ◽  
Global Developmental Delay

AbstractGlucose transporter type-1 deficiency syndrome (Glut1 DS) is a rare disorder with various manifestations. Early diagnosis is crucial because treatment with the ketogenic diet can lead to clinical improvement. Here, we report the cases of two siblings with Glut1 DS and one of them presented with sleep disorder which is a rare and atypical manifestation of Glut1 DS. Patient 1 was a 3.5-year-old boy who presented with paroxysmal loss of tone and weakness of the whole body with unresponsiveness after waking up. He also had excessive daytime sleepiness, insomnia, and restless sleep. His other clinical findings included focal seizures, paroxysmal exercise-induced dyskinesia (PED), ataxia, mild global developmental delay, and hyperactivity. Patient 2 was a 5.5-year-old boy who presented with drug-resistant focal epilepsy, global developmental delay, paroxysmal dystonia, and ataxia. A novel heterozygous nonsense variant of SLC2A1, c.1177G > T (p.Glu393*), classified as a pathogenic variant, was identified in both patients, but not in their parents' blood. After treatment with the modified Atkins diet, their neurological functions significantly improved. In conclusion, we reported two siblings with variable phenotypes of Glut1 DS with a novel nonsense mutation. Although sleep disorder and daytime somnolence were the nonclassical manifestations of Glut1 DS, the diagnostic evaluation of possible Glut1 DS in patients presented with daytime sleepiness, particularly in cases with the cooccurrence of seizures or movement disorders should be considered.

scholarly journals Verbal and nonverbal outcomes of toddlers with and without autism spectrum disorder, language delay, and global developmental delay

2018 ◽  
Vol 3 ◽  
pp. 239694151876476 ◽  
Author(s):  
Abigail D Delehanty ◽  
Sheri Stronach ◽  
Whitney Guthrie ◽  
Elizabeth Slate ◽  
Amy M Wetherby
Keyword(s):  
Young Children ◽  
Developmental Delay ◽  
Social Communication ◽  
Expressive Language ◽  
Developmental Outcomes ◽  
Autism Spectrum ◽  
Global Developmental Delay ◽  
Developmental Level ◽  
Communication Delays ◽  
Children With Asd

Background and Aims Children with autism spectrum disorder (ASD) exhibit a heterogeneous clinical phenotype with wide variability in their language and intellectual profiles that complicates efforts at early detection. There is limited research examining observational measures to characterize differences between young children with and without ASD and co-occurring language delay (LD) and global developmental delay (GDD). The first aim of this study was to compare early social communication measured in the second year of life in children diagnosed at age 3 with ASD, developmental delays (DD), and typical development (TD). The second aim was to compare early social communication in six subgroups of children: ASD, ASD+LD, ASD+GDD, LD, GDD, and TD. Our third aim was to determine the collective and unique contributions of early social communication to predict verbal and nonverbal developmental outcomes at three years of age for children with and without ASD. Methods Analyses of covariance controlling for maternal education were employed to examine group differences in social communication in 431 toddlers recruited through screening in primary care. Multiple linear regression analyses were conducted to evaluate associations between the Communication and Symbolic Behavior Scales (CSBS) Behavior Sample composite standard scores and Mullen Scales of Early Learning T scores for children with and without ASD. Results Distinct patterns of early social communication were evident by 20 months. Children with TD differed significantly from children with ASD and DD on all three CSBS Behavior Sample composites. Children with ASD had significantly lower scores than those with DD and TD on the social and symbolic composites. Among the six subgroups, all three composites of the CSBS Behavior Sample differentiated children with TD from all other subgroups. Children with ASD+GDD scored significantly lower than all other subgroups on social and symbolic composites. Patterns of social communication emerged for children with and without ASD, which held among subgroups divided by developmental level. The CSBS Behavior Sample social and symbolic composites contributed unique variance in predicting developmental outcomes in both groups. The speech composite contributed unique variance to expressive language, receptive language, and visual reception in children without ASD, and contributed uniquely to expressive language only for children with ASD. Conclusions The CSBS Behavior Sample, an observational measure for children aged 12–24 months, detected social communication delays and explained a significant amount of variance in verbal and nonverbal outcomes a year later in this large sample of young children grouped by ASD diagnosis and developmental level. Implications In light of the continued search for early predictors of ASD and developmental delay, our findings underscore the importance of monitoring early social communication skills, including the expression of emotions, eye gaze, gestures, rate of communication, joint attention, understanding words, and object use in play. There is a need for clinical utility of screening and evaluation tools that can detect social communication delays in very young children. This would enable intervention for infants and toddlers who show social communication delays which may be early signs for ASD or other DD, rather than waiting to confirm a formal diagnosis.

A homozygous missense mutation inHERC2associated with global developmental delay and autism spectrum disorder

2012 ◽  
Vol 33 (12) ◽  
pp. 1639-1646 ◽  
Author(s):  
Erik G. Puffenberger ◽  
Robert N. Jinks ◽  
Heng Wang ◽  
Baozhong Xin ◽  
Christopher Fiorentini ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Missense Mutation ◽  
Developmental Delay ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Global Developmental Delay ◽  
Homozygous Missense Mutation

scholarly journals A de novo TOP2B variant associated with global developmental delay and autism spectrum disorder

2020 ◽  
Vol 8 (3) ◽  
Author(s):  
Takuya Hiraide ◽  
Seiji Watanabe ◽  
Tomoko Matsubayashi ◽  
Kumiko Yanagi ◽  
Mitsuko Nakashima ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Developmental Delay ◽  
De Novo ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Global Developmental Delay

scholarly journals Expanding the Phenotype of TUBB2A-Related Tubulinopathy: Three Cases of a Novel, Heterozygous TUBB2A Pathogenic Variant p.Gly98Arg

2020 ◽  
pp. 1-8
Author(s):  
Lindsey Schmidt ◽  
Karen E. Wain ◽  
Catherine Hajek ◽  
Juvianee I. Estrada-Veras ◽  
Maria J. Guillen Sacoto ◽  
...  
Keyword(s):  
Developmental Delay ◽  
Case Series ◽  
Missense Variant ◽  
Autism Spectrum ◽  
Cortical Dysplasia ◽  
Global Developmental Delay ◽  
Tubulin Genes ◽  
Pathogenic Variants ◽  
Brain Malformations ◽  
History Of

Tubulinopathies are a group of conditions caused by variants in 6 tubulin genes that present with a spectrum of brain malformations. One of these conditions is <i>TUBB2A</i>-related tubulinopathy. Currently, there are 9 reported individuals with pathogenic variants within the <i>TUBB2A</i> gene, with common manifestations including, but not limited to, global developmental delay, seizures, cortical dysplasia, and dysmorphic corpus callosum. We report 3 patients identified by exome and genome sequencing to have a novel, pathogenic, missense variant in <i>TUBB2A</i> (p.Gly98Arg). They presented similarly with intellectual disability, hypotonia, and global developmental delay and varied with respect to the type of cortical brain malformation, seizure history, diagnosis of autism spectrum disorder, and other features. This case series expands the natural history of <i>TUBB2A</i>-related tubulinopathy while describing the presentation of a novel, pathogenic, missense variant in 3 patients.

scholarly journals Whole Exome Sequencing Reveals a Novel AUTS2 In-Frame Deletion in a Boy with Global Developmental Delay, Absent Speech, Dysmorphic Features, and Cerebral Anomalies

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 229
Author(s):  
Pietro Palumbo ◽  
Ester Di Muro ◽  
Maria Accadia ◽  
Mario Benvenuto ◽  
Marilena Carmela Di Giacomo ◽  
...  
Keyword(s):  
Corpus Callosum ◽  
Exome Sequencing ◽  
Developmental Delay ◽  
Whole Exome Sequencing ◽  
Molecular Mechanisms ◽  
Autism Spectrum ◽  
Copy Number Variations ◽  
Cerebellar Vermis ◽  
Global Developmental Delay ◽  
Whole Exome

Neurodevelopmental disorders (NDDs) are a group of highly prevalent, clinically and genetically heterogeneous pediatric disorders comprising, according to the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-V), intellectual disability, developmental delay, autism spectrum disorders, and other neurological and cognitive disorders manifesting in the developmental age. To date, more than 1000 genes have been implicated in the etiopathogenesis of NNDs. Among them, AUTS2 (OMIM # 607270) encodes a protein involved in neural migration and neuritogenesis, and causes NNDs with different molecular mechanisms including copy number variations, single or multiple exonic deletion and single nucleotide variants. We describes a 9-year-old boy with global developmental delay, absent speech, minor craniofacial anomalies, hypoplasia of the cerebellar vermis and thinning of the corpus callosum, resulted carrier of the de novo AUTS2 c.1603_1626del deletion at whole exome sequencing (WES) predicted to cause the loss of eight amino acids [p.(His535_Thr542del)]. Notably, our patient is the first reported so far in medical literature carrying an in-frame deletion and the first in which absent language, hypoplasia of the cerebellar vermis and thinning of the corpus callosum has been observed thus useful to expand the molecular spectrum of AUTS2 pathogenic variants and to broaden our knowledge on the clinical phenotype associated.

scholarly journals Case Report: A Novel GNB1 Mutation Causes Global Developmental Delay With Intellectual Disability and Behavioral Disorders

2021 ◽  
Vol 12 ◽  
Author(s):  
Jorge Diogo Da Silva ◽  
Marta Daniela Costa ◽  
Bruno Almeida ◽  
Fátima Lopes ◽  
Patrícia Maciel ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
Developmental Delay ◽  
Behavioral Disorders ◽  
Psychiatric Symptoms ◽  
Novel Mutation ◽  
Autism Spectrum ◽  
Global Developmental Delay ◽  
Missense Mutations ◽  
Protein Subunit ◽  
Neurodevelopmental Disease

Diseases of neurodevelopment mostly exhibit neurological and psychiatric symptoms that go from very mild to extremely severe. While the etiology of most cases of neurodevelopmental disease is still unknown, the discovery of underlying genetic causes is rapidly increasing, with hundreds of genes being currently implicated as disease-causing. Here, we report a clinical case of a patient with a previously undiagnosed syndrome comprising severe global developmental delay, intellectual disability, and behavioral disorders (such as attention-deficit/hyperactivity disorder, autism spectrum disorder and recurrent bouts of aggressive behavior). After genetic testing, a pathogenic variant was detected in the GNB1 gene, which codes for the G-protein subunit β1. The detected variant (c.217G&gt;A, p.A73T) has not been previously reported in any of the 58 published cases of GNB1 encephalopathy. However, it localizes to the mutational hotspot in exons 6 and 7 in which 88% of all missense mutations occur. An in silico model predicts that this mutation is likely to disrupt the WD40 domain of the GNB1 protein, which is required for its interaction with other G-proteins and, consequently, for downstream signal transduction. In conclusion, we reported an additional GNB1 encephalopathy patient, bearing a novel mutation, taking another step toward a better understanding of its clinical presentation and prospective development of treatments for the disease.

scholarly journals Relationship between Autistic Traits and Nutrient Intake among Japanese Children and Adolescents

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2258
Author(s):  
Hiromasa Tsujiguchi ◽  
Sakae Miyagi ◽  
Thao Thi Thu Nguyen ◽  
Akinori Hara ◽  
Yasuki Ono ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Nutrient Intake ◽  
Age Groups ◽  
Pantothenic Acid ◽  
Autism Spectrum ◽  
Food Selectivity ◽  
Analysis Of Covariance ◽  
Nutrient Intakes ◽  
Cross Sectional ◽  
The Mean

Increased food selectivity among children with autism spectrum disorder (ASD) may lead to nutritional inadequacy. The present study examined differences in nutrient intake between children and adolescents with and without ASD. We utilized cross-sectional data from the ongoing population Shika Town rural Japanese study. The participants were 1276 Japanese pupils and students aged between 7 and 15 years. ASD traits were evaluated using the Autism Spectrum Screening Questionnaire (ASSQ). Nutrient intake was assessed using a food frequency questionnaire. A one-way analysis of covariance (one-way ANCOVA) was performed to compare the mean nutrient intakes between participants with and without ASD traits. A two-way ANCOVA was conducted to compare the mean nutrient intakes among participants with and without ASD traits in different age groups (children and adolescents). The results obtained showed that the intake of carbohydrates and slightly lower intakes of protein, fat, calcium, magnesium, phosphorus, iron, zinc, retinol, vitamin B2, vitamin B12, folic acid, and pantothenic acid were higher among children and adolescents with ASD than among those without ASD. No interactions were observed between the autistic groups and age groups, excluding energy intakes. The present results indicate the importance of screening the nutrient intakes of ASD children and adolescents.

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