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Child and Adolescent Psychiatric... Jul 2007Turner syndrome is a neurogenetic disorder characterized by partial or complete monosomy-X. It is associated with certain physical and medical features, including... (Review)
Review
Turner syndrome is a neurogenetic disorder characterized by partial or complete monosomy-X. It is associated with certain physical and medical features, including estrogen deficiency, short stature, and increased risk for several diseases, with cardiac conditions being among the most serious. The cognitive-behavioral phenotype associated with the syndrome includes strengths in verbal domains with impairments in visuospatial, executive function, and emotion processing. Less is known regarding psychosocial and psychiatric functioning in Turner syndrome, but essential aspects of psychotherapeutic treatment plans are suggested. Future investigations should include continued genetic studies and determination of candidate genes for physical and cognitive features. Multimodal, interdisciplinary studies are essential for identifying optimal, syndrome-specific interventions for improving the lives of individuals who have Turner syndrome.
Topics: Cognition Disorders; Human Growth Hormone; Humans; Psychology; Turner Syndrome
PubMed: 17562588
DOI: 10.1016/j.chc.2007.02.004 -
Molecular Genetics & Genomic Medicine Mar 2022Angelman syndrome (AS) is a rare neurogenetic disorder present in approximately 1/12,000 individuals and characterized by developmental delay, cognitive impairment,... (Review)
Review
BACKGROUND
Angelman syndrome (AS) is a rare neurogenetic disorder present in approximately 1/12,000 individuals and characterized by developmental delay, cognitive impairment, motor dysfunction, seizures, gastrointestinal concerns, and abnormal electroencephalographic background. AS is caused by absent expression of the paternally imprinted gene UBE3A in the central nervous system. Disparities in the management of AS are a major problem in preparing for precision therapies and occur even in patients with access to experts and recognized clinics. AS patients receive care based on collective provider experience due to limited evidence-based literature. We present a consensus statement and comprehensive literature review that proposes a standard of care practices for the management of AS at a critical time when therapeutics to alter the natural history of the disease are on the horizon.
METHODS
We compiled the key recognized clinical features of AS based on consensus from a team of specialists managing patients with AS. Working groups were established to address each focus area with committees comprised of providers who manage >5 individuals. Committees developed management guidelines for their area of expertise. These were compiled into a final document to provide a framework for standardizing management. Evidence from the medical literature was also comprehensively reviewed.
RESULTS
Areas covered by working groups in the consensus document include genetics, developmental medicine, psychology, general health concerns, neurology (including movement disorders), sleep, psychiatry, orthopedics, ophthalmology, communication, early intervention and therapies, and caregiver health. Working groups created frameworks, including flowcharts and tables, to help with quick access for providers. Data from the literature were incorporated to ensure providers had review of experiential versus evidence-based care guidelines.
CONCLUSION
Standards of care in the management of AS are keys to ensure optimal care at a critical time when new disease-modifying therapies are emerging. This document is a framework for providers of all familiarity levels.
Topics: Angelman Syndrome; Humans; Standard of Care
PubMed: 35150089
DOI: 10.1002/mgg3.1843 -
Seminars in Pediatric Neurology Jul 2021Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder characterized by loss of motor neurons leading to muscle weakness and atrophy. The United States'... (Review)
Review
Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder characterized by loss of motor neurons leading to muscle weakness and atrophy. The United States' Food and Drug Administration's (FDA) approval of nusinersen, onasemnogene abeparvovec, and risdiplam for SMA has challenged existing treatment paradigms with multiple treatment options, a new natural history of the disease, and an emerging understanding of the importance of early and pre-symptomatic treatment. The profound impact of early, pre-symptomatic treatment has led to the creation of a neurogenetics urgency for newly identified patients with SMA, a novel problem for neurologists more accustomed to a more methodical approach to diagnosis and care. Implementation of newborn screening programs has helped facilitate early diagnosis and treatment, but challenges remain in overcoming administrative and procedural hurdles that can lead to treatment delays. Herein I discuss 2 cases that highlight the importance of early treatment, as well as gaps in our understanding of the progression of SMA in pre-symptomatic infants.
Topics: Genetic Therapy; Humans; Infant; Infant, Newborn; Muscular Atrophy, Spinal; Neonatal Screening; Neurosciences; Spinal Muscular Atrophies of Childhood; United States
PubMed: 34183144
DOI: 10.1016/j.spen.2021.100899 -
Neuron Jan 2017To decipher neural circuits underlying brain functions, viral tracers are widely applied to map input and output connectivity of neuronal populations. Despite the...
To decipher neural circuits underlying brain functions, viral tracers are widely applied to map input and output connectivity of neuronal populations. Despite the successful application of retrograde transsynaptic viruses for identifying presynaptic neurons of transduced neurons, analogous anterograde transsynaptic tools for tagging postsynaptically targeted neurons remain under development. Here, we discovered that adeno-associated viruses (AAV1 and AAV9) exhibit anterograde transsynaptic spread properties. AAV1-Cre from transduced presynaptic neurons effectively and specifically drives Cre-dependent transgene expression in selected postsynaptic neuronal targets, thus allowing axonal tracing and functional manipulations of the latter input-defined neuronal population. Its application in superior colliculus (SC) reveals that SC neuron subpopulations receiving corticocollicular projections from auditory and visual cortex specifically drive flight and freezing, two different types of defense behavior, respectively. Together with an intersectional approach, AAV-mediated anterograde transsynaptic tagging can categorize neurons by their inputs and molecular identity, and allow forward screening of distinct functional neural pathways embedded in complex brain circuits.
Topics: Animals; Auditory Cortex; Behavior, Animal; Cerebral Cortex; DNA Nucleotidyltransferases; Dependovirus; Escape Reaction; Freezing Reaction, Cataleptic; Integrases; Mice; Neural Pathways; Neurons; Superior Colliculi; Synapses; Visual Cortex
PubMed: 27989459
DOI: 10.1016/j.neuron.2016.11.045 -
Human Molecular Genetics Oct 2021Huntington's disease (HD) is a devastating neurogenetic disorder whose familial nature and progressive course were first described in the 19th century but for which no... (Review)
Review
Huntington's disease (HD) is a devastating neurogenetic disorder whose familial nature and progressive course were first described in the 19th century but for which no disease-modifying treatment is yet available. Through the active participation of HD families, this disorder has acted as a flagship for the application of human molecular genetic strategies to identify disease genes, understand pathogenesis and identify rational targets for development of therapies.
Topics: Alleles; Animals; Biomarkers; Disease Management; Disease Susceptibility; Genetic Association Studies; Genetic Linkage; Genetic Predisposition to Disease; Humans; Huntington Disease; Models, Biological
PubMed: 34169318
DOI: 10.1093/hmg/ddab170 -
Nature Neuroscience Apr 2021Anxiety is a negative emotional state that is overly displayed in anxiety disorders and depression. Although anxiety is known to be controlled by distributed brain...
Anxiety is a negative emotional state that is overly displayed in anxiety disorders and depression. Although anxiety is known to be controlled by distributed brain networks, key components for its initiation, maintenance and coordination with behavioral state remain poorly understood. Here, we report that anxiogenic stressors elicit acute and prolonged responses in glutamatergic neurons of the mouse medial preoptic area (mPOA). These neurons encode extremely negative valence and mediate the induction and expression of anxiety-like behaviors. Conversely, mPOA GABA-containing neurons encode positive valence and produce anxiolytic effects. Such opposing roles are mediated by competing local interactions and long-range projections of neurons to the periaqueductal gray. The two neuronal populations antagonistically regulate anxiety-like and parental behaviors: anxiety is reduced, while parenting is enhanced and vice versa. Thus, by evaluating negative and positive valences through distinct but interacting circuits, the mPOA coordinates emotional state and social behavior.
Topics: Animals; Anxiety; Behavior, Animal; Female; GABAergic Neurons; Glutamine; Male; Mice; Mice, Inbred C57BL; Neurons; Preoptic Area; Social Behavior; Stress, Psychological
PubMed: 33526942
DOI: 10.1038/s41593-020-00784-3 -
Journal of Neurology, Neurosurgery, and... Dec 2022Abnormal expanded GGC repeats within the gene has been confirmed as the genetic mechanism for most Asian patients with neuronal intranuclear inclusion disease (NIID).... (Observational Study)
Observational Study
BACKGROUND
Abnormal expanded GGC repeats within the gene has been confirmed as the genetic mechanism for most Asian patients with neuronal intranuclear inclusion disease (NIID). This cross-sectional observational study aimed to characterise the clinical features of -related NIID in China.
METHODS
Patients with -related NIID underwent an evaluation of clinical symptoms, a neuropsychological assessment, electrophysiological examination, MRI and skin biopsy.
RESULTS
In the 247 patients with -related NIID, 149 cases were sporadic, while 98 had a positive family history. The most common manifestations were paroxysmal symptoms (66.8%), autonomic dysfunction (64.0%), movement disorders (50.2%), cognitive impairment (49.4%) and muscle weakness (30.8%). Based on the initial presentation and main symptomology, NIID was divided into four subgroups: dementia dominant (n=94), movement disorder dominant (n=63), paroxysmal symptom dominant (n=61) and muscle weakness dominant (n=29). Clinical (42.7%) and subclinical (49.1%) peripheral neuropathies were common in all types. Typical diffusion-weighted imaging subcortical lace signs were more frequent in patients with dementia (93.9%) and paroxysmal symptoms types (94.9%) than in those with muscle weakness (50.0%) and movement disorders types (86.4%). GGC repeat sizes were negatively correlated with age of onset (r=-0.196, p<0.05), and in the muscle weakness-dominant type (median 155.00), the number of repeats was much higher than in the other three groups (p<0.05). In NIID pedigrees, significant genetic anticipation was observed (p<0.05) without repeat instability (p=0.454) during transmission.
CONCLUSIONS
NIID is not rare; however, it is usually misdiagnosed as other diseases. Our results help to extend the known clinical spectrum of -related NIID.
Topics: Humans; Muscle Weakness; Peripheral Nervous System Diseases; Cross-Sectional Studies; Intranuclear Inclusion Bodies; Dementia; Movement Disorders
PubMed: 36150844
DOI: 10.1136/jnnp-2022-329772 -
Practical Neurology May 2021The costs of whole-genome sequencing have rapidly decreased, and it is being increasingly deployed in large-scale clinical research projects and introduced into routine...
The costs of whole-genome sequencing have rapidly decreased, and it is being increasingly deployed in large-scale clinical research projects and introduced into routine clinical care. This will lead to rapid diagnoses for patients with genetic disease but also introduces uncertainty because of the diversity of human genomes and the potential difficulties in annotating new genetic variants for individual patients and families. Here we outline the steps in organising whole-genome sequencing for patients in the neurology clinic and emphasise that close liaison between the clinician and the laboratory is essential.
PubMed: 33972362
DOI: 10.1136/practneurol-2020-002561 -
Brain Sciences Aug 2017Few movement disorders seem to make a straightforward approach to diagnosis and treatment more difficult and frustrating than myoclonus, due to its plethora of causes... (Review)
Review
Few movement disorders seem to make a straightforward approach to diagnosis and treatment more difficult and frustrating than myoclonus, due to its plethora of causes and its variable classifications. Nevertheless, in recent years, exciting advances have been made in the elucidation of the pathophysiology and genetic basis of many disorders presenting with myoclonus. Here, we provide a review of all of the important types of myoclonus encountered in pediatric and adult neurology, with an emphasis on the recent developments that have led to a deeper understanding of this intriguing phenomenon. An up-to-date list of the genetic basis of all major myoclonic disorders is presented. Randomized studies are scarce in myoclonus therapy, but helpful pragmatic approaches at diagnosis as well as treatment have been recently suggested.
PubMed: 28805718
DOI: 10.3390/brainsci7080103 -
Frontiers in Synaptic Neuroscience 2023Synaptic neurotransmitter release is an evolutionarily conserved process that mediates rapid information transfer between neurons as well as several peripheral tissues.... (Review)
Review
Synaptic neurotransmitter release is an evolutionarily conserved process that mediates rapid information transfer between neurons as well as several peripheral tissues. Release of neurotransmitters are ensured by successive events such as synaptic vesicle docking and priming that prepare synaptic vesicles for rapid fusion. These events are orchestrated by interaction of different presynaptic proteins and are regulated by presynaptic calcium. Recent studies have identified various mutations in different components of neurotransmitter release machinery resulting in aberrant neurotransmitter release, which underlie a wide spectrum of psychiatric and neurological symptoms. Here, we review how these genetic alterations in different components of the core neurotransmitter release machinery affect the information transfer between neurons and how aberrant synaptic release affects nervous system function.
PubMed: 37066095
DOI: 10.3389/fnsyn.2023.1148957