17 results on '"Carly Hyde"'
Search Results
2. The diagnostic journey of genetically defined neurodevelopmental disorders
- Author
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Juliana Simon, Carly Hyde, Vidya Saravanapandian, Rujuta Wilson, Charlotte Distefano, Aaron Besterman, and Shafali Jeste
- Subjects
Neurodevelopmental disorders ,Genetic testing ,Diagnostic journey ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Abstract Background The development of advanced genetic technologies has resulted in rapid identification of genetic etiologies of neurodevelopmental disorders (NDDs) and has transformed the classification and diagnosis of various NDDs. However, diagnostic genetics has far outpaced our ability to provide timely medical counseling, guidance, and care for patients with genetically defined NDDs. These patients and their caregivers present with an unmet need for care coordination across multiple domains including medical, developmental, and psychiatric care and for educational resources and guidance from care professionals. After a genetic diagnosis is made, families also face several barriers in access to informed diagnostic evaluations and medical support. Methods As part of Care and Research in Neurogenetics (CARING), a multidisciplinary clinical program for children and adults with neurogenetic disorders, we conducted qualitative clinical interviews about the diagnostic journey of families. This included the overall timeline to receiving diagnoses, experiences before and after diagnosis, barriers to care, and resources that helped them to navigate the diagnostic process. Results A total of 37 interviews were conducted with parents of children ages 16 months to 33 years. Several key themes were identified: (1) delays between initial caregiver observations and formal developmental or genetic diagnoses; (2) practical barriers to clinical evaluation and care, including long wait times for an appointment, lack of insurance coverage, availability of local evaluations, transportation difficulties, and native language differences; (3) the importance of being part of a patient advocacy group to help navigate the diagnostic journey; and (4) unique challenges faced by adults (18 years or older). Conclusions Families of children with complex neurodevelopmental and genetic disabilities face numerous challenges in finding adequate medical care and services for their child. They experience considerable delays in receiving timely diagnoses and face significant barriers that further delay the process of receiving access to services needed for the child’s continued care. The gaps indicated in this study speak to the need for more comprehensive coordination of care for patients with intellectual and developmental disabilities, as well as the development of systematic, disorder-specific resources both for providers and families in order to improve patient outcomes.
- Published
- 2022
- Full Text
- View/download PDF
3. Properties of beta oscillations in Dup15q syndrome
- Author
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Vidya Saravanapandian, Joel Frohlich, Joerg F. Hipp, Carly Hyde, Aaron W. Scheffler, Peyman Golshani, Edwin H. Cook, Lawrence T. Reiter, Damla Senturk, and Shafali S. Jeste
- Subjects
Dup15q syndrome ,Autism ,Biomarkers ,EEG ,GABA ,UBE3A ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Abstract Background Duplications of 15q11.2-q13.1 (Dup15q syndrome) are highly penetrant for autism, intellectual disability, hypotonia, and epilepsy. The 15q region harbors genes critical for brain development, particularly UBE3A and a cluster of gamma-aminobutyric acid type A receptor (GABAAR) genes. We recently described an electrophysiological biomarker of the syndrome, characterized by excessive beta oscillations (12–30 Hz), resembling electroencephalogram (EEG) changes induced by allosteric modulation of GABAARs. In this follow-up study, we tested a larger cohort of children with Dup15q syndrome to comprehensively examine properties of this EEG biomarker that would inform its use in future clinical trials, specifically, its (1) relation to basic clinical features, such as age, duplication type, and epilepsy; (2) relation to behavioral characteristics, such as cognition and adaptive function; (3) stability over time; and (4) reproducibility of the signal in clinical EEG recordings. Methods We computed EEG power and beta peak frequency (BPF) in a cohort of children with Dup15q syndrome (N = 41, age range 9–189 months). To relate EEG parameters to clinical (study 1) and behavioral features (study 2), we examined age, duplication type, epilepsy, cognition, and daily living skills (DLS) as predictors of beta power and BPF. To evaluate stability over time (study 3), we derived the intraclass correlation coefficients (ICC) from beta power and BPF computed from children with multiple EEG recordings (N = 10, age range 18–161 months). To evaluate reproducibility in a clinical setting (study 4), we derived ICCs from beta power computed from children (N = 8, age range 19–96 months), who had undergone both research EEG and clinical EEG. Results The most promising relationships between EEG and clinical traits were found using BPF. BPF was predicted both by epilepsy status (R 2 = 0.11, p = 0.038) and the DLS component of the Vineland Adaptive Behavior Scale (R 2 = 0.17, p = 0.01). Beta power and peak frequency showed high stability across repeated visits (beta power ICC = 0.93, BPF ICC = 0.92). A reproducibility analysis revealed that beta power estimates are comparable between research and clinical EEG (ICC = 0.94). Conclusions In this era of precision health, with pharmacological and neuromodulatory therapies being developed and tested for specific genetic etiologies of neurodevelopmental disorders, quantification and examination of mechanistic biomarkers can greatly improve clinical trials. To this end, the robust beta oscillations evident in Dup15q syndrome are clinically reproducible and stable over time. With future preclinical and computational studies that will help disentangle the underlying mechanism, it is possible that this biomarker could serve as a robust measure of drug target engagement or a proximal outcome measure in future disease modifying intervention trials.
- Published
- 2020
- Full Text
- View/download PDF
4. A telehealth approach to improving clinical trial access for infants with tuberous sclerosis complex
- Author
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Carly Hyde, Maria Pizzano, Nicole M. McDonald, Charles A. Nelson, Connie Kasari, Elizabeth A. Thiele, and Shafali S. Jeste
- Subjects
Telehealth ,Early intervention ,Tuberous sclerosis complex ,Clinical trial recruitment ,Behavioral intervention ,Autism spectrum disorder ,Neurosciences. Biological psychiatry. Neuropsychiatry ,RC321-571 - Abstract
Abstract Background Research in rare genetic syndromes associated with ASD is often hampered by the wide geographic distribution of families and the presence of medical comorbidities, such as epilepsy, that may preclude travel to clinical sites. These challenges can limit the sample size and generalizability of the cohorts included in both natural history studies and clinical trials. Tuberous sclerosis complex (TSC) is a rare genetic syndrome that confers an elevated risk for autism spectrum disorder (ASD), with social communication delays identified in this population as early as 12 months of age. Early identification of risk necessitates parallel testing of early intervention, prompting the first randomized controlled clinical trial of behavioral intervention for infants with TSC (NCT03422367). However, considerable early recruitment challenges have mandated the systematic identification of enrollment barriers followed by modification of the study design to address these barriers. Methods Caregivers were interviewed regarding barriers to enrollment (phase 1). Adaptations to the intervention were made to address these barriers (phase 2). Outcomes based on this modification to the study design were defined by enrollment rate and participant demographics. Results Qualitative reports from caregivers indicated that distance and time were the primary barriers to clinical trial enrollment. The intervention was then modified to a remote model, with at-home, parent-delivered intervention, and weekly video conferencing with interventionists at the study sites. Enrollment increased 10-fold (from 3 to 30 participants) within 1 year and included a more diverse and clinically representative cohort of infants. Conclusion The design and implementation of more scalable methods to disseminate research remotely can substantially improve access to clinical trials in rare neurodevelopmental disorders. The lessons learned from this trial can serve as a model for future studies not only in rare conditions, but in other populations that lack adequate access, such as families with limited financial or clinical resources. Continued efforts will further refine delivery methods to enhance efficiency and ease of these delivery systems for families.
- Published
- 2020
- Full Text
- View/download PDF
5. Mechanisms underlying the EEG biomarker in Dup15q syndrome
- Author
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Joel Frohlich, Lawrence T. Reiter, Vidya Saravanapandian, Charlotte DiStefano, Scott Huberty, Carly Hyde, Stormy Chamberlain, Carrie E. Bearden, Peyman Golshani, Andrei Irimia, Richard W. Olsen, Joerg F. Hipp, and Shafali S. Jeste
- Subjects
Dup15q syndrome ,GABA ,UBE3A ,Biomarkers ,Autism ,EEG ,Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Abstract Background Duplications of 15q11.2-q13.1 (Dup15q syndrome), including the paternally imprinted gene UBE3A and three nonimprinted gamma-aminobutyric acid type-A (GABAA) receptor genes, are highly penetrant for neurodevelopmental disorders such as autism spectrum disorder (ASD). To guide targeted treatments of Dup15q syndrome and other forms of ASD, biomarkers are needed that reflect molecular mechanisms of pathology. We recently described a beta EEG phenotype of Dup15q syndrome, but it remains unknown which specific genes drive this phenotype. Methods To test the hypothesis that UBE3A overexpression is not necessary for the beta EEG phenotype, we compared EEG from a reference cohort of children with Dup15q syndrome (n = 27) to (1) the pharmacological effects of the GABAA modulator midazolam (n = 12) on EEG from healthy adults, (2) EEG from typically developing (TD) children (n = 14), and (3) EEG from two children with duplications of paternal 15q (i.e., the UBE3A-silenced allele). Results Peak beta power was significantly increased in the reference cohort relative to TD controls. Midazolam administration recapitulated the beta EEG phenotype in healthy adults with a similar peak frequency in central channels (f = 23.0 Hz) as Dup15q syndrome (f = 23.1 Hz). Both paternal Dup15q syndrome cases displayed beta power comparable to the reference cohort. Conclusions Our results suggest a critical role for GABAergic transmission in the Dup15q syndrome beta EEG phenotype, which cannot be explained by UBE3A dysfunction alone. If this mechanism is confirmed, the phenotype may be used as a marker of GABAergic pathology in clinical trials for Dup15q syndrome.
- Published
- 2019
- Full Text
- View/download PDF
6. Correction to: Mechanisms underlying the EEG biomarker in Dup15q syndrome
- Author
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Joel Frohlich, Lawrence T. Reiter, Vidya Saravanapandian, Charlotte DiStefano, Scott Huberty, Carly Hyde, Stormy Chamberlain, Carrie E. Bearden, Peyman Golshani, Andrei Irimia, Richard W. Olsen, Joerg F. Hipp, and Shafali S. Jeste
- Subjects
Neurology. Diseases of the nervous system ,RC346-429 - Abstract
Following publication of the original article [1], we have been notified that the Ethics statement of the articles should be changed. The Ethics statement now reads:
- Published
- 2019
- Full Text
- View/download PDF
7. Properties of beta oscillations in Dup15q syndrome
- Author
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Damla Şentürk, Joel Frohlich, Shafali S. Jeste, Lawrence T. Reiter, Vidya Saravanapandian, Carly Hyde, Edwin H. Cook, Joerg F. Hipp, Peyman Golshani, and Aaron Scheffler
- Subjects
medicine.medical_specialty ,Neurology ,Cognitive Neuroscience ,Dup15q syndrome ,Autism ,Audiology ,Dup15q ,Electroencephalography ,Pathology and Forensic Medicine ,lcsh:RC321-571 ,03 medical and health sciences ,Epilepsy ,GABA ,0302 clinical medicine ,Intellectual Disability ,medicine ,Humans ,0501 psychology and cognitive sciences ,EEG ,Child ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,medicine.diagnostic_test ,business.industry ,Research ,05 social sciences ,Neurodevelopmental disorders ,UBE3A ,Neuropsychology ,Infant ,Reproducibility of Results ,medicine.disease ,Vineland Adaptive Behavior Scale ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,Biomarker (medicine) ,Neurology (clinical) ,business ,030217 neurology & neurosurgery ,Biomarkers ,050104 developmental & child psychology ,Follow-Up Studies - Abstract
BackgroundDuplications of 15q11.2-q13.1 (Dup15q syndrome) are highly penetrant for autism, intellectual disability, hypotonia, and epilepsy. The 15q region harbors genes critical for brain development, particularlyUBE3Aand a cluster of gamma-aminobutyric acid type A receptor (GABAAR) genes. We recently described an electrophysiological biomarker of the syndrome, characterized by excessive beta oscillations (12–30 Hz), resembling electroencephalogram (EEG) changes induced by allosteric modulation of GABAARs. In this follow-up study, we tested a larger cohort of children with Dup15q syndrome to comprehensively examine properties of this EEG biomarker that would inform its use in future clinical trials, specifically, its (1) relation to basic clinical features, such as age, duplication type, and epilepsy; (2) relation to behavioral characteristics, such as cognition and adaptive function; (3) stability over time; and (4) reproducibility of the signal in clinical EEG recordings.MethodsWe computed EEG power and beta peak frequency (BPF) in a cohort of children with Dup15q syndrome (N= 41, age range 9–189 months). To relate EEG parameters to clinical (study 1) and behavioral features (study 2), we examined age, duplication type, epilepsy, cognition, and daily living skills (DLS) as predictors of beta power and BPF. To evaluate stability over time (study 3), we derived the intraclass correlation coefficients (ICC) from beta power and BPF computed from children with multiple EEG recordings (N= 10, age range 18–161 months). To evaluate reproducibility in a clinical setting (study 4), we derived ICCs from beta power computed from children (N= 8, age range 19–96 months), who had undergone both research EEG and clinical EEG.ResultsThe most promising relationships between EEG and clinical traits were found using BPF. BPF was predicted both by epilepsy status (R2= 0.11,p= 0.038) and the DLS component of the Vineland Adaptive Behavior Scale (R2= 0.17,p= 0.01). Beta power and peak frequency showed high stability across repeated visits (beta power ICC = 0.93, BPF ICC = 0.92). A reproducibility analysis revealed that beta power estimates are comparable between research and clinical EEG (ICC = 0.94).ConclusionsIn this era of precision health, with pharmacological and neuromodulatory therapies being developed and tested for specific genetic etiologies of neurodevelopmental disorders, quantification and examination of mechanistic biomarkers can greatly improve clinical trials. To this end, the robust beta oscillations evident in Dup15q syndrome are clinically reproducible and stable over time. With future preclinical and computational studies that will help disentangle the underlying mechanism, it is possible that this biomarker could serve as a robust measure of drug target engagement or a proximal outcome measure in future disease modifying intervention trials.
- Published
- 2020
8. A telehealth approach to improving clinical trial access for infants with tuberous sclerosis complex
- Author
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Maria Pizzano, Charles A. Nelson, Carly Hyde, Nicole M. McDonald, Elizabeth A. Thiele, Shafali S. Jeste, and Connie Kasari
- Subjects
Parents ,Male ,Autism Spectrum Disorder ,Autism ,Telehealth ,Clinical trial recruitment ,Early intervention ,0302 clinical medicine ,Tuberous Sclerosis ,Psychology ,030212 general & internal medicine ,Autism spectrum disorder ,Child ,Pediatric ,education.field_of_study ,Clinical Trials as Topic ,Neuropsychology ,Telemedicine ,Mental Health ,Child, Preschool ,Cohort ,Female ,Adult ,medicine.medical_specialty ,Remote delivery ,Intellectual and Developmental Disabilities (IDD) ,Cognitive Neuroscience ,Clinical Trials and Supportive Activities ,Population ,Pathology and Forensic Medicine ,lcsh:RC321-571 ,03 medical and health sciences ,Rare Diseases ,Clinical Research ,Intervention (counseling) ,Behavioral and Social Science ,medicine ,Humans ,Generalizability theory ,education ,Preschool ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,business.industry ,Research ,Prevention ,Patient Selection ,Neurosciences ,Infant ,medicine.disease ,Brain Disorders ,Quality Education ,Clinical trial ,Behavioral intervention ,Tuberous sclerosis complex ,Family medicine ,Pediatrics, Perinatology and Child Health ,Videoconferencing ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Background Research in rare genetic syndromes associated with ASD is often hampered by the wide geographic distribution of families and the presence of medical comorbidities, such as epilepsy, that may preclude travel to clinical sites. These challenges can limit the sample size and generalizability of the cohorts included in both natural history studies and clinical trials. Tuberous sclerosis complex (TSC) is a rare genetic syndrome that confers an elevated risk for autism spectrum disorder (ASD), with social communication delays identified in this population as early as 12 months of age. Early identification of risk necessitates parallel testing of early intervention, prompting the first randomized controlled clinical trial of behavioral intervention for infants with TSC (NCT03422367). However, considerable early recruitment challenges have mandated the systematic identification of enrollment barriers followed by modification of the study design to address these barriers. Methods Caregivers were interviewed regarding barriers to enrollment (phase 1). Adaptations to the intervention were made to address these barriers (phase 2). Outcomes based on this modification to the study design were defined by enrollment rate and participant demographics. Results Qualitative reports from caregivers indicated that distance and time were the primary barriers to clinical trial enrollment. The intervention was then modified to a remote model, with at-home, parent-delivered intervention, and weekly video conferencing with interventionists at the study sites. Enrollment increased 10-fold (from 3 to 30 participants) within 1 year and included a more diverse and clinically representative cohort of infants. Conclusion The design and implementation of more scalable methods to disseminate research remotely can substantially improve access to clinical trials in rare neurodevelopmental disorders. The lessons learned from this trial can serve as a model for future studies not only in rare conditions, but in other populations that lack adequate access, such as families with limited financial or clinical resources. Continued efforts will further refine delivery methods to enhance efficiency and ease of these delivery systems for families.
- Published
- 2020
9. The Diagnostic Journey of Genetically Defined Neurodevelopmental Disorders
- Author
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Juliana Simon, Rujuta B. Wilson, Charlotte DiStefano, Carly Hyde, Vidya Saravandapandian, Aaron D Besterman, and Shafali S Jeste
- Abstract
Background The development of advanced genetic technologies has resulted in rapid identification of genetic etiologies of neurodevelopmental disorders (NDDs) and has transformed the classification and diagnosis of various NDDs. However, diagnostic genetics has far outpaced our ability to provide timely medical counseling, guidance, and care for patients with genetically defined NDDs. These patients and their caregivers present with an unmet need for care coordination across multiple domains including medical, developmental, and psychiatric care, and for educational resources and guidance from care professionals. After a genetic diagnosis is made, families also face several barriers in access to informed diagnostic evaluations and medical support. Methods As part of Care and Research in Neurogenetics (CARING), a multidisciplinary clinical program for children and adults with neurogenetic disorders, we conducted qualitative clinical interviews about the diagnostic journey of families. This included the overall timeline to receiving diagnoses, experiences before and after diagnosis, barriers to care, and resources that helped them to navigate the diagnostic process. Results A total of 37 interviews were conducted with parents of children ages 16 months to 33 years. Several key themes were identified: 1) delays between initial caregiver observations of developmental delays and formal developmental or genetic diagnoses; 2) practical barriers to clinical evaluation and care, including long wait times for an appointment, lack of insurance coverage, availability of local evaluations, transportation difficulties, and native language differences; 3) the importance of being part of a patient advocacy group to help navigate the diagnostic journey; and (4) unique challenges faced by adults (18 years or older). Conclusions Families of children with complex neurodevelopmental and genetic disabilities face numerous challenges in finding adequate medical care and services for their child. They experience considerable delays in receiving timely diagnoses and face significant barriers that further delay the process of receiving access to services needed for the child’s continued care. The gaps indicated in this study speak to the need for more comprehensive coordination of care for patients with intellectual and developmental disabilities, as well as the development of systematic, disorder-specific resources both for providers and families in order to improve patient outcomes.
- Published
- 2021
10. Changes in access to educational and healthcare services for individuals with intellectual and developmental disabilities during COVID‐19 restrictions
- Author
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A. Halladay, Shafali S. Jeste, Rujuta B. Wilson, A. Thurm, Charlotte DiStefano, Carly Hyde, M. Porath, and S. Ray
- Subjects
030506 rehabilitation ,medicine.medical_specialty ,Telemedicine ,Clinical Neurology ,Telehealth ,computer.software_genre ,03 medical and health sciences ,Videoconferencing ,Arts and Humanities (miscellaneous) ,Health care ,Intellectual disability ,medicine ,0501 psychology and cognitive sciences ,Service (business) ,business.industry ,05 social sciences ,Rehabilitation ,medicine.disease ,Psychiatry and Mental health ,Neurology ,Autism spectrum disorder ,Family medicine ,Autism ,Neurology (clinical) ,0305 other medical science ,business ,Psychology ,computer ,050104 developmental & child psychology - Abstract
Background COVID-19 restrictions have significantly limited access to in-person educational and healthcare services for all, including individuals with intellectual and developmental disabilities (IDDs). The objectives of this online survey that included both national and international families were to capture changes in access to healthcare and educational services for individuals with IDDs that occurred shortly after restrictions were initiated and to survey families on resources that could improve services for these individuals. Methods This was an online survey for caregivers of individuals with (1) a genetic diagnosis and (2) a neurodevelopmental diagnosis, including developmental delay, intellectual disability, autism spectrum disorder or epilepsy. The survey assessed (1) demographics, (2) changes in access to educational and healthcare services and (3) available and preferred resources to help families navigate the changes in service allocation. Results Of the 818 responses (669 within the USA and 149 outside of the USA), most families reported a loss of at least some educational or healthcare services. Seventy-four per cent of parents reported that their child lost access to at least one therapy or education service, and 36% of respondents lost access to a healthcare provider. Only 56% reported that their child received at least some continued services through tele-education. Those that needed to access healthcare providers did so primarily through telemedicine. Telehealth (both tele-education and telemedicine) was reported to be helpful when available, and caregivers most often endorsed a need for an augmentation of these remote delivery services, such as 1:1 videoconference sessions, as well as increased access to 1:1 aides in the home. Conclusions COVID-19 restrictions have greatly affected access to services for individuals with syndromic IDDs. Telehealth may provide opportunities for delivery of care and education in a sustainable way, not only as restrictions endure but also after they have been lifted.
- Published
- 2020
- Full Text
- View/download PDF
11. The Neurodevelopmental and Motor Phenotype of SCA21 (ATX-TMEM240)
- Author
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Rujuta B. Wilson, Julian A. Martinez, Shafali S. Jeste, Emma D Burdekin, Charlotte DiStefano, Carly Hyde, Brent L. Fogel, Jessica E. Rexach, and Tabitha Safari
- Subjects
Male ,medicine.medical_specialty ,Ataxia ,Adolescent ,Context (language use) ,050105 experimental psychology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Neurodevelopmental disorder ,Physical medicine and rehabilitation ,Cognition ,Intellectual Disability ,Intellectual disability ,medicine ,Humans ,0501 psychology and cognitive sciences ,Child ,Gait ,Motor skill ,Spinocerebellar Degenerations ,Cerebellar ataxia ,business.industry ,Communication ,05 social sciences ,Brain ,Membrane Proteins ,medicine.disease ,Magnetic Resonance Imaging ,Phenotype ,Autism spectrum disorder ,Motor Skills ,Pediatrics, Perinatology and Child Health ,Mutation ,Spinocerebellar ataxia ,Female ,Neurology (clinical) ,medicine.symptom ,Symptom Assessment ,business ,030217 neurology & neurosurgery - Abstract
Spinocerebellar ataxia type 21 (SCA21/ATX-TMEM240) is a rare form of cerebellar ataxia that commonly presents with motor, cognitive, and behavioral impairments. Although these features have been identified as part of the clinical manifestations of SCA21, the neurodevelopmental disorders associated with SCA21 have not been well studied or described. Here we present extensive phenotypic data for 3 subjects from an SCA21 family in the United States. Genetic testing demonstrated the c.196 G>A (p.Gly66Arg) variant to be a second recurrent mutation associated with the disorder. Standardized developmental assessment revealed significant deficits in cognition, adaptive function, motor skills, and social communication with 2 of the subjects having diagnoses of autism spectrum disorder, which has never been described in SCA21. Quantitative gait analysis showed markedly abnormal spatiotemporal gait variables indicative of poor gait control and cerebellar as well as noncerebellar dysfunction. Clinical evaluation also highlighted a striking variability in clinical symptoms, with greater ataxia correlating with greater severity of neurodevelopmental disorder diagnoses. Notably, neurodevelopmental outcomes have improved with intervention over time. Taken together, this case series identifies that the manifestation of neurodevelopmental disorders is a key feature of SCA21 and may precede the presence of motor abnormalities. Furthermore, the coexistence of ataxia and neurodevelopmental disorders in these subjects suggests a role for spinocerebellar pathways in both outcomes. The findings in this study highlight the importance of evaluation of neurodevelopmental concerns in the context of progressive motor abnormalities and the need for timely intervention to ultimately improve quality of life for individuals with SCA21.
- Published
- 2020
12. Quantitative Gait Analysis in Duplication 15q Syndrome and Nonsyndromic ASD
- Author
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David Elashoff, Beth A. Smith, Arnaud Gouelle, Carly Hyde, Rujuta B. Wilson, Tabitha Safari, Abigail Dickinson, Shafali S. Jeste, Andrew M. Wilson, Performance, Santé, Métrologie, Société - EA 7507 (PSMS), and Université de Reims Champagne-Ardenne (URCA)
- Subjects
Male ,Autism Spectrum Disorder ,Autism ,Trisomy ,0302 clinical medicine ,Intellectual disability ,Medicine ,Psychology ,genetic syndrome ,gait function ,Genetics (clinical) ,Pediatric ,General Neuroscience ,05 social sciences ,Genetic disorder ,Syndrome ,Mental Health ,Autism spectrum disorder ,Female ,Gait Analysis ,050104 developmental & child psychology ,Human ,medicine.medical_specialty ,Language delay ,Intellectual and Developmental Disabilities (IDD) ,Clinical Sciences ,Developmental & Child Psychology ,Dup15q ,behavioral disciplines and activities ,Article ,Chromosomes ,03 medical and health sciences ,Physical medicine and rehabilitation ,Clinical Research ,mental disorders ,Humans ,0501 psychology and cognitive sciences ,[PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph] ,quantitative gait analysis ,Chromosomes, Human, Pair 15 ,motor impairments ,business.industry ,Pair 15 ,Neurosciences ,duplication 15q syndrome ,medicine.disease ,Gait ,Brain Disorders ,Gait analysis ,Neurology (clinical) ,business ,030217 neurology & neurosurgery - Abstract
Motor impairments occur frequently in genetic syndromes highly penetrant for autism spectrum disorder (syndromic ASD) and in individuals with ASD without a genetic diagnosis (nonsyndromic ASD). In particular, abnormalities in gait in ASD have been linked to language delay, ASD severity, and likelihood of having a genetic disorder. Quantitative measures of motor function can improve our ability to evaluate motor differences in individuals with syndromic and nonsyndromic ASD with varying levels of intellectual disability and adaptive skills. To evaluate this methodology, we chose to use quantitative gait analysis to study duplication 15q syndrome (dup15q syndrome), a genetic disorder highly penetrant for motor delays, intellectual disability, and ASD. We evaluated quantitative gait variables in individuals with dup15q syndrome (n = 39) and nonsyndromic ASD (n = 21) and compared these data to a reference typically developing cohort. We found a gait pattern of slow pace, poor postural control, and large gait variability in dup15q syndrome. Our findings improve characterization of motor function in dup15q syndrome and nonsyndromic ASD. Quantitative gait analysis can be used as a translational method and can improve our identification of clinical endpoints to be used in treatment trials for these syndromes. Autism Res 2020, 13: 1102-1110. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Motor impairments, particularly abnormalities in walking, occur frequently in genetic syndromes highly penetrant for autism spectrum disorder (syndromic ASD). Here, using quantitative gait analysis, we find that individuals with duplication 15q syndrome have an atypical gait pattern that differentiates them from typically developing and nonsyndromic ASD individuals. Our findings improve motor characterization in dup15q syndrome and nonsyndromic ASD.
- Published
- 2020
13. Improving Developmental Abilities in Infants With Tuberous Sclerosis Complex: A Pilot Behavioral Intervention Study
- Author
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Nicole M. McDonald, April Boin Choi, Amanda Gulsrud, Connie Kasari, Carly Hyde, Charles A. Nelson, and Shafali S. Jeste
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,Pediatric Research Initiative ,Intellectual and Developmental Disabilities (IDD) ,Autism ,Clinical Trials and Supportive Activities ,Clinical Sciences ,autism spectrum disorder ,Developmental & Child Psychology ,tuberous sclerosis complex ,Article ,law.invention ,03 medical and health sciences ,Tuberous sclerosis ,0302 clinical medicine ,Rare Diseases ,Randomized controlled trial ,law ,Tuberous Sclerosis ,Clinical Research ,030225 pediatrics ,Intervention (counseling) ,Intellectual disability ,Behavioral and Social Science ,Developmental and Educational Psychology ,medicine ,Psychology ,0501 psychology and cognitive sciences ,Pediatric ,business.industry ,Prevention ,05 social sciences ,behavioral intervention ,Neurosciences ,Cognition ,medicine.disease ,Child development ,Brain Disorders ,Quality Education ,Psychiatry and Mental health ,early intervention ,Mental Health ,Autism spectrum disorder ,Pediatrics, Perinatology and Child Health ,business ,050104 developmental & child psychology ,Clinical psychology - Abstract
Tuberous sclerosis complex (TSC) is a rare genetic syndrome that confers risk for neurodevelopmental disorders, including autism spectrum disorder and intellectual disability. Delays in social communication and early cognitive abilities are observable as early as 9 months of age in children with TSC; however, there have been no studies of early behavioral intervention in TSC. We conducted a pilot study of an evidence-based, parent-mediated behavioral intervention focused on improving early social communication and play skills in 5 children with TSC (aged 1-3 years). Participants showed maintenance and sometimes gains in developmental abilities, relative to peers, following intervention. Parents generally found the intervention to be helpful and were able to administer the intervention with fidelity. Preliminary results demonstrate initial feasibility of an early play-based, parent-mediated intervention and support the need for a large-scale, randomized clinical trial in TSC.
- Published
- 2020
14. Measurement of Sleep Behaviors in Chromosome 15q11.2-13.1 Duplication (Dup15q Syndrome)
- Author
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Carly Hyde, Jamie Barstein, Shafali S. Jeste, Vidya Saravanapandian, and Charlotte DiStefano
- Subjects
Electroencephalography ,Dup15q ,Chromosomes ,Epilepsy ,Arts and Humanities (miscellaneous) ,Intellectual Disability ,Intellectual disability ,Developmental and Educational Psychology ,medicine ,Humans ,Child ,Sleep disorder ,medicine.diagnostic_test ,General Medicine ,medicine.disease ,Sleep in non-human animals ,Hypotonia ,Psychiatry and Mental health ,Neuropsychology and Physiological Psychology ,Pediatrics, Perinatology and Child Health ,Autism ,Neurology (clinical) ,medicine.symptom ,Psychology ,Sleep ,Clinical psychology - Abstract
Duplication of chromosome 15q11.2-q13.1 (dup15q syndrome) results in hypotonia, intellectual disability (ID), and autism symptomatology. Clinical electroencephalography has shown abnormal sleep physiology, but no studies have characterized sleep behaviors. The present study used the Children's Sleep Habits Questionnaire (CSHQ) in 42 people with dup15q syndrome to examine the clinical utility of this questionnaire and quantify behavioral sleep patterns in dup15q syndrome. Individuals with fully completed forms (56%) had higher cognitive abilities than those with partially completed forms. Overall, caregivers indicated a high rate of sleep disturbance, though ratings differed by epilepsy status. Results suggest that clinicians should use caution when using standardized questionnaires and consider epilepsy status when screening for sleep problems in dup15q syndrome.
- Published
- 2019
15. Mechanisms underlying the EEG biomarker in Dup15q syndrome
- Author
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Joerg F. Hipp, Joel Frohlich, Carly Hyde, Scott Huberty, Richard W. Olsen, Peyman Golshani, Shafali S. Jeste, Lawrence T. Reiter, Vidya Saravanapandian, Carrie E. Bearden, Stormy J. Chamberlain, Andrei Irimia, and Charlotte DiStefano
- Subjects
Male ,Autism ,Dup15q syndrome ,Electroencephalography ,Bioinformatics ,lcsh:RC346-429 ,Cohort Studies ,Fathers ,GABA ,0302 clinical medicine ,Receptors ,2.1 Biological and endogenous factors ,EEG ,Aetiology ,Child ,GABRG3 ,Pediatric ,0303 health sciences ,biology ,medicine.diagnostic_test ,Neurodevelopmental disorders ,3. Good health ,Psychiatry and Mental health ,Phenotype ,Mental Health ,Autism spectrum disorder ,GABRA5 ,Female ,Human ,Adult ,Midazolam ,Intellectual and Developmental Disabilities (IDD) ,Clinical Sciences ,Dup15q ,Chromosomes ,03 medical and health sciences ,Developmental Neuroscience ,Clinical Research ,Intellectual Disability ,GABRB3 ,medicine ,UBE3A ,Genetics ,Humans ,Molecular Biology ,lcsh:Neurology. Diseases of the nervous system ,030304 developmental biology ,Chromosome Aberrations ,Chromosomes, Human, Pair 15 ,business.industry ,GABA-A ,Research ,Pair 15 ,Neurosciences ,Receptors, GABA-A ,medicine.disease ,Brain Disorders ,biology.protein ,business ,Genomic imprinting ,030217 neurology & neurosurgery ,Biomarkers ,Developmental Biology - Abstract
Background Duplications of 15q11.2-q13.1 (Dup15q syndrome), including the paternally imprinted gene UBE3A and three nonimprinted gamma-aminobutyric acid type-A (GABAA) receptor genes, are highly penetrant for neurodevelopmental disorders such as autism spectrum disorder (ASD). To guide targeted treatments of Dup15q syndrome and other forms of ASD, biomarkers are needed that reflect molecular mechanisms of pathology. We recently described a beta EEG phenotype of Dup15q syndrome, but it remains unknown which specific genes drive this phenotype. Methods To test the hypothesis that UBE3A overexpression is not necessary for the beta EEG phenotype, we compared EEG from a reference cohort of children with Dup15q syndrome (n = 27) to (1) the pharmacological effects of the GABAA modulator midazolam (n = 12) on EEG from healthy adults, (2) EEG from typically developing (TD) children (n = 14), and (3) EEG from two children with duplications of paternal 15q (i.e., the UBE3A-silenced allele). Results Peak beta power was significantly increased in the reference cohort relative to TD controls. Midazolam administration recapitulated the beta EEG phenotype in healthy adults with a similar peak frequency in central channels (f = 23.0 Hz) as Dup15q syndrome (f = 23.1 Hz). Both paternal Dup15q syndrome cases displayed beta power comparable to the reference cohort. Conclusions Our results suggest a critical role for GABAergic transmission in the Dup15q syndrome beta EEG phenotype, which cannot be explained by UBE3A dysfunction alone. If this mechanism is confirmed, the phenotype may be used as a marker of GABAergic pathology in clinical trials for Dup15q syndrome. Electronic supplementary material The online version of this article (10.1186/s13229-019-0280-6) contains supplementary material, which is available to authorized users.
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- 2019
16. Correction to: Mechanisms underlying the EEG biomarker in Dup15q syndrome
- Author
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Stormy J. Chamberlain, Andrei Irimia, Joel Frohlich, Joerg F. Hipp, Carly Hyde, Shafali S. Jeste, Lawrence T. Reiter, Peyman Golshani, Carrie E. Bearden, Charlotte DiStefano, Richard W. Olsen, Scott Huberty, and Vidya Saravanapandian
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medicine.medical_specialty ,Statement (logic) ,Clinical Sciences ,Dup15q ,Electroencephalography ,lcsh:RC346-429 ,03 medical and health sciences ,0302 clinical medicine ,Developmental Neuroscience ,medicine ,Psychiatry ,Molecular Biology ,lcsh:Neurology. Diseases of the nervous system ,030304 developmental biology ,0303 health sciences ,medicine.diagnostic_test ,business.industry ,Neuropsychology ,Neurosciences ,Correction ,Human genetics ,Psychiatry and Mental health ,Biomarker (medicine) ,business ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
Following publication of the original article [1], we have been notified that the Ethics statement of the articles should be changed. The Ethics statement now reads
- Published
- 2019
17. Measurement of Sleep Behaviors in Chromosome 15q11.2-13.1 Duplication (Dup15q Syndrome).
- Author
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Barstein J, Jeste S, Saravanapandian V, Hyde C, and Distefano C
- Subjects
- Child, Chromosomes, Electroencephalography, Humans, Sleep, Epilepsy genetics, Intellectual Disability genetics
- Abstract
Duplication of chromosome 15q11.2-q13.1 (dup15q syndrome) results in hypotonia, intellectual disability (ID), and autism symptomatology. Clinical electroencephalography has shown abnormal sleep physiology, but no studies have characterized sleep behaviors. The present study used the Children's Sleep Habits Questionnaire (CSHQ) in 42 people with dup15q syndrome to examine the clinical utility of this questionnaire and quantify behavioral sleep patterns in dup15q syndrome. Individuals with fully completed forms (56%) had higher cognitive abilities than those with partially completed forms. Overall, caregivers indicated a high rate of sleep disturbance, though ratings differed by epilepsy status. Results suggest that clinicians should use caution when using standardized questionnaires and consider epilepsy status when screening for sleep problems in dup15q syndrome., (©AAIDD.)
- Published
- 2021
- Full Text
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