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Orphanet Journal of Rare Diseases Dec 2010Huntington disease (HD) is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric... (Review)
Review
Huntington disease (HD) is a rare neurodegenerative disorder of the central nervous system characterized by unwanted choreatic movements, behavioral and psychiatric disturbances and dementia. Prevalence in the Caucasian population is estimated at 1/10,000-1/20,000. Mean age at onset of symptoms is 30-50 years. In some cases symptoms start before the age of 20 years with behavior disturbances and learning difficulties at school (Juvenile Huntington's disease; JHD). The classic sign is chorea that gradually spreads to all muscles. All psychomotor processes become severely retarded. Patients experience psychiatric symptoms and cognitive decline. HD is an autosomal dominant inherited disease caused by an elongated CAG repeat (36 repeats or more) on the short arm of chromosome 4p16.3 in the Huntingtine gene. The longer the CAG repeat, the earlier the onset of disease. In cases of JHD the repeat often exceeds 55. Diagnosis is based on clinical symptoms and signs in an individual with a parent with proven HD, and is confirmed by DNA determination. Pre-manifest diagnosis should only be performed by multidisciplinary teams in healthy at-risk adult individuals who want to know whether they carry the mutation or not. Differential diagnoses include other causes of chorea including general internal disorders or iatrogenic disorders. Phenocopies (clinically diagnosed cases of HD without the genetic mutation) are observed. Prenatal diagnosis is possible by chorionic villus sampling or amniocentesis. Preimplantation diagnosis with in vitro fertilization is offered in several countries. There is no cure. Management should be multidisciplinary and is based on treating symptoms with a view to improving quality of life. Chorea is treated with dopamine receptor blocking or depleting agents. Medication and non-medical care for depression and aggressive behavior may be required. The progression of the disease leads to a complete dependency in daily life, which results in patients requiring full-time care, and finally death. The most common cause of death is pneumonia, followed by suicide.
Topics: Adolescent; Adult; Age of Onset; Aged; Child; Child, Preschool; Chorea; Cognition Disorders; Humans; Huntington Disease; Mental Disorders; Middle Aged; Young Adult
PubMed: 21171977
DOI: 10.1186/1750-1172-5-40 -
Translational Neurodegeneration Feb 2021Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes. Paroxysmal kinesigenic... (Review)
Review
Paroxysmal dyskinesias are a group of neurological diseases characterized by intermittent episodes of involuntary movements with different causes. Paroxysmal kinesigenic dyskinesia (PKD) is the most common type of paroxysmal dyskinesia and can be divided into primary and secondary types based on the etiology. Clinically, PKD is characterized by recurrent and transient attacks of involuntary movements precipitated by a sudden voluntary action. The major cause of primary PKD is genetic abnormalities, and the inheritance pattern of PKD is mainly autosomal-dominant with incomplete penetrance. The proline-rich transmembrane protein 2 (PRRT2) was the first identified causative gene of PKD, accounting for the majority of PKD cases worldwide. An increasing number of studies has revealed the clinical and genetic characteristics, as well as the underlying mechanisms of PKD. By seeking the views of domestic experts, we propose an expert consensus regarding the diagnosis and treatment of PKD to help establish standardized clinical evaluation and therapies for PKD. In this consensus, we review the clinical manifestations, etiology, clinical diagnostic criteria and therapeutic recommendations for PKD, and results of genetic analyses in PKD patients performed in domestic hospitals.
Topics: China; Chorea; Consensus; Dystonia; Humans; Membrane Proteins; Nerve Tissue Proteins
PubMed: 33588936
DOI: 10.1186/s40035-021-00231-8 -
Journal of Veterinary Internal Medicine May 2021Movement disorders are a heterogeneous group of clinical syndromes in humans and animals characterized by involuntary movements without changes in consciousness. Canine...
Movement disorders are a heterogeneous group of clinical syndromes in humans and animals characterized by involuntary movements without changes in consciousness. Canine movement disorders broadly include tremors, peripheral nerve hyperexcitability disorders, paroxysmal dyskinesia, and dystonia. Of these, canine paroxysmal dyskinesias remain one of the more difficult to identify and characterize in dogs. Canine paroxysmal dyskinesias include an array of movement disorders in which there is a recurrent episode of abnormal, involuntary, movement. In this consensus statement, we recommend standard terminology for describing the various movement disorders with an emphasis on paroxysmal dyskinesia, as well as a preliminary classification and clinical approach to reporting cases. In the clinical approach to movement disorders, we recommend categorizing movements into hyperkinetic vs hypokinetic, paroxysmal vs persistent, exercise-induced vs not related to exercise, using a detailed description of movements using the recommended terminology presented here, differentiating movement disorders vs other differential diagnoses, and then finally, determining whether the paroxysmal dyskinesia is due to either inherited or acquired etiologies. This consensus statement represents a starting point for consistent reporting of clinical descriptions and terminology associated with canine movement disorders, with additional focus on paroxysmal dyskinesia. With consistent reporting and identification of additional genetic mutations responsible for these disorders, our understanding of the phenotype, genotype, and pathophysiology will continue to develop and inform further modification of these recommendations.
Topics: Animals; Chorea; Dog Diseases; Dogs; Dyskinesias; Mutation; Phenotype
PubMed: 33769611
DOI: 10.1111/jvim.16108 -
Developmental Medicine and Child... Mar 2021Paediatric movement disorders (PMDs) comprise a large group of disorders (tics, myoclonus, tremor, dystonia, chorea, Parkinsonism, ataxia), often with mixed phenotypes....
Paediatric movement disorders (PMDs) comprise a large group of disorders (tics, myoclonus, tremor, dystonia, chorea, Parkinsonism, ataxia), often with mixed phenotypes. Determination of the underlying aetiology can be difficult given the broad differential diagnosis and the complexity of the genotype-phenotype relationships. This can make the diagnostic process time-consuming and difficult. In this overview, we present a diagnostic approach for PMDs, with emphasis on genetic causes. This approach can serve as a framework to lead the clinician through the diagnostic process in eight consecutive steps, including recognition of the different movement disorders, identification of a clinical syndrome, consideration of acquired causes, genetic testing including next-generation sequencing, post-sequencing phenotyping, and interpretation of test results. The aim of this approach is to increase the recognition and diagnostic yield in PMDs. WHAT THIS PAPER ADDS: An up-to-date description and diagnostic framework for testing of paediatric movement disorders is presented. The framework helps to determine which patients will benefit from next-generation sequencing.
Topics: Adolescent; Ataxia; Child; Chorea; Diagnosis, Differential; Dystonia; Humans; Movement Disorders; Pediatrics; Phenotype
PubMed: 33150968
DOI: 10.1111/dmcn.14721 -
Journal of General Internal Medicine Aug 2022
Topics: Chorea; Diabetes Mellitus; Diabetic Ketoacidosis; Humans
PubMed: 35590024
DOI: 10.1007/s11606-022-07651-w -
Current Opinion in Rheumatology Jul 2012To give an overview of the current hypotheses of the pathogenesis of rheumatic fever and group A streptococcal autoimmune sequelae of the heart valve and brain. (Review)
Review
PURPOSE OF REVIEW
To give an overview of the current hypotheses of the pathogenesis of rheumatic fever and group A streptococcal autoimmune sequelae of the heart valve and brain.
RECENT FINDINGS
Human monoclonal antibodies (mAbs) derived from rheumatic heart disease have provided evidence for crossreactive autoantibodies that target the dominant group A streptococcal epitope of the group A carbohydrate, N-acetyl-beta-D-glucosamine (GlcNAc), and heart valve endothelium, laminin and laminar basement membrane. T cells in peripheral blood and in rheumatic heart valves revealed the presence of T cells crossreactive with streptococcal M protein and cardiac myosin. For initiation of disease, evidence suggests a two-hit hypothesis for antibody attack on the valve endothelium with subsequent extravasation of T cells through activated endothelium into the valve to form granulomatous lesions and Aschoff bodies. Autoantibodies against the group A streptococcal carbohydrate epitope GlcNAc and cardiac myosin and its peptides appear during progression of rheumatic heart disease. However, autoantibodies against collagen that are not crossreactive may form because of the release of collagen from damaged valve or to responses to collagen bound in vitro by certain serotypes of streptococci. In Sydenham chorea, human mAbs derived from disease target the group A carbohydrate epitope GlcNAc and gangliosides and dopamine receptors found on the surface of neuronal cells in the brain. Human mAbs and autoantibodies in Sydenham chorea were found to signal neuronal cells and activate calcium calmodulin-dependent protein kinase II (CaMKII) in neuronal cells and recognize the intracellular protein biomarker tubulin.
SUMMARY
To summarize, pathogenic mechanisms of crossreactive autoantibodies which target the valve in rheumatic heart disease and the neuronal cell in Sydenham chorea share a common streptococcal epitope GlcNAc and target intracellular biomarkers of disease including cardiac myosin in the myocardium and tubulin, a protein abundant in the brain. However, intracellular antigens are not believed to be the basis for disease. The theme of molecular mimicry in streptococcal autoimmune sequelae is the recognition of targeted intracellular biomarker antigens such as cardiac myosin and brain tubulin, while targeting extracellular membrane antigens such as laminin on the valve surface endothelium or lysoganglioside and dopamine receptors in the brain. Antibody binding to these cell surface antigens may lead to valve damage in rheumatic heart disease or neuropsychiatric behaviors and involuntary movements in Sydenham chorea.
Topics: Antigens, Bacterial; Autoantibodies; Autoimmunity; Chorea; Cross Reactions; Humans; Molecular Mimicry; Neurons; Rheumatic Heart Disease; Streptococcus pyogenes
PubMed: 22617826
DOI: 10.1097/BOR.0b013e32835461d3 -
Neurology India 2023
Topics: Humans; Dyskinesias; Chorea; Diabetes Mellitus
PubMed: 37148098
DOI: 10.4103/0028-3886.375388 -
Current Opinion in Neurology Aug 2016Chorea presenting in childhood and adulthood encompasses several neurological disorders, both degenerative and nonprogressive, often with a genetic basis. In this... (Review)
Review
PURPOSE OF REVIEW
Chorea presenting in childhood and adulthood encompasses several neurological disorders, both degenerative and nonprogressive, often with a genetic basis. In this review, we discuss how modern genomic technologies are expanding our knowledge of monogenic choreic syndromes and advancing our insight into the molecular mechanisms responsible for chorea.
RECENT FINDINGS
A genome-wide association study in Huntington's disease identified genetic disease modifiers involved in controlling DNA repair mechanisms and stability of the HTT trinucleotide repeat expansion. Chorea is the cardinal feature of newly recognized genetic entities, ADCY5 and PDE10A-related choreas, with onset in infancy and childhood. A phenotypic overlap between chorea, ataxia, epilepsy, and neurodevelopmental disorders is becoming increasingly evident.
SUMMARY
The differential diagnosis of genetic conditions presenting with chorea has considerably widened, permitting a molecular diagnosis and an improved prognostic definition in an expanding number of cases. The identification of Huntington's disease genetic modifiers and new chorea-causing gene mutations has allowed the initial recognition of converging molecular pathways underlying medium spiny neurons degeneration and dysregulation of normal development and activity of basal ganglia circuits. Signalling downstream of dopamine receptors and control of cAMP levels represent a very promising target for the development of new aetiology-based treatments for chorea and other hyperkinetic disorders.
Topics: Cerebellar Ataxia; Chorea; Genome-Wide Association Study; Humans; Huntington Disease; Mutation
PubMed: 27257945
DOI: 10.1097/WCO.0000000000000352 -
European Neurology 2022Chorea may be present in a number of diseases including hereditary disorders. Major advances have occurred in our understanding of the genetic background of those... (Review)
Review
BACKGROUND
Chorea may be present in a number of diseases including hereditary disorders. Major advances have occurred in our understanding of the genetic background of those disorders, and the present short review aims at highlighting the most salient ones.
SUMMARY
Chorea is one of the major manifestations of Huntington's disease. However, there are a number of other diseases, in which chorea is present as well and their list is in constant increase thanks to the availability of advanced molecular genetic diagnostic techniques. Finding of new genes followed by the investigation of further cases with part of the phenotype first described often leads to the recognition of additional aspects of the disorders, thus widening the scope of investigation and management. Likewise, assessment of genetic variations associated with specific aspects of the phenotype, in a way similar to approaches established in nongenetic disorders, has improved our understanding of phenotype variation. Knowledge on genetic background of chorea has ameliorated our diagnostic approaches. Furthermore, it opens new therapeutic strategies aimed at modifying expression both of the genes primarily implicated as the ones involved in further phenotype modification.
KEY MESSAGES
Recent research on the genetic background of disorders with chorea has provided data, which can now better guide differential diagnostic investigations in practical ways. Furthermore, they provide avenues for research on the disease mechanisms opening the door for clinical therapeutic trials.
Topics: Chorea; Humans; Huntington Disease; Phenotype
PubMed: 36049455
DOI: 10.1159/000526237 -
The Psychiatric Clinics of North America Dec 1997Huntington's disease is a genetically inherited degenerative neuropsychiatric disorder, characterized by motor alterations, including involuntary movements such as... (Review)
Review
Huntington's disease is a genetically inherited degenerative neuropsychiatric disorder, characterized by motor alterations, including involuntary movements such as chorea, dementia and psychiatric disturbances. In this article, the authors review the clinical features of the disease. They also analyze some genetic and pathophysiologic aspects, that can help to improve our understanding of this disorder involving the basal ganglia.
Topics: Basal Ganglia; Behavioral Symptoms; Disease Progression; Genetic Markers; Humans; Huntington Disease; Nerve Degeneration; Palliative Care
PubMed: 9443350
DOI: 10.1016/s0193-953x(05)70345-2