Early in the disease the memory deficits in HD are usually much less severe than in Alzheimer disease. The overall cognitive and behavioral syndrome in individuals with HD is more similar to frontotemporal dementia than to Alzheimer disease. Attention and concentration are involved early [ Peinemann et al ], resulting in easy distractibility.
Language functions are relatively preserved, but a diminished level of syntactic complexity, cortical speech abnormalities, paraphasic errors, and word-finding difficulties are common in late stages. Neuropsychologic testing reveals impaired visuospatial abilities, particularly in late stages of the disease. Lack of awareness, especially of one's own disabilities, is common [ Ho et al , Bates et al ]. Psychiatric disturbances. Individuals with HD develop significant personality changes, affective psychosis, or schizophrenic psychosis [ Rosenblatt ].
Prior to onset of HD, they tend to score high on measures of depression, hostility, obsessive-compulsiveness, anxiety, and psychoticism [ Duff et al ]. Unlike the progressive cognitive and motor disturbances, the psychiatric changes tend not to progress with disease severity [ Epping et al ]. Behavioral disturbances such as intermittent explosiveness, apathy, aggression, alcohol abuse, sexual dysfunction and deviations, and increased appetite are frequent.
Delusions, often paranoid, are common. Hallucinations are less common. Depression and suicide risk. The incidence of depression in preclinical and symptomatic individuals is more than twice the general population [ Paulsen et al b , Marshall et al ]. The etiology of depression in HD is unclear; it may be a pathologic rather than a psychological consequence of having the disease [ Slaughter et al , Pouladi et al ]. Suicide and suicide ideation are common in persons with HD, but the incidence rate changes with disease course and predictive testing results [ Larsson et al , Robins Wahlin , van Duijn et al ].
The critical periods for suicide risk were found to be just prior to receiving a diagnosis and later, when affected individuals experience a loss of independence [ Baliko et al , Paulsen et al a , Eddy et al ]. It is also common for persons with HD to demonstrate increased appetite and energy expenditure [ Pratley et al , Trejo et al , Gaba et al ].
Insomnia and daytime somnolence may also be present, although this is more commonly due to psychiatric changes, depression, or chorea [ Videnovic et al ]. The primary neuropathologic feature of HD is degeneration of neurons in the caudate and putamen as well as the cerebral cortex [ Waldvogel et al ]. The preferential degeneration of enkephalin-containing, medium spiny neurons of the indirect pathway of movement control in the basal ganglia provides the neurobiologic basis for chorea [ Galvan et al ].
The additional loss of substance P-containing medium spiny neurons of the direct pathway results in akinesia and dystonia [ Galvan et al ]. Region-specific patterns of neuronal loss in the basal ganglia and cortex may underlie the most evident symptoms in affected individuals and could contribute to the phenotypic variability among individuals [ Thu et al , Hadzi et al , Kim et al , Waldvogel et al , Mehrabi et al ]. Intraneuronal inclusions containing huntingtin, the protein expressed from HTT , are also a prominent neuropathologic feature of the disease. Imaging studies provide additional support for the clinical diagnosis of HD and are valuable tools for studying progression of the disease [ Biglan et al , Paulsen , Tabrizi et al , Tabrizi et al , Tabrizi et al ].
In addition to significant striatal atrophy in symptomatic individuals, regional and whole-brain gray and white matter changes have been detected [ Majid et al , Tabrizi et al , Tabrizi et al , Tabrizi et al ]. Furthermore, MRI studies have revealed progressive gray and white matter atrophy many years prior to predicted disease onset [ Tabrizi et al , Tabrizi et al , Tabrizi et al ]. Numerous studies in recent years have used neuroimaging to elucidate the clinical progression of HD, with the specific interest of using these objective measures in clinical trials for testing efficacy of experimental therapeutics [ Tabrizi et al , Tabrizi et al ].
The motor, cognitive, and psychiatric disturbances observed in adult HD are also observed in juvenile HD, but the clinical presentation of these disturbances is different. Intermediate alleles IA. An individual with a CAG repeat in the range is not believed to be at risk of developing HD but, because of instability in the CAG tract, may be at risk of having a child with an allele in the pathogenic CAG range [ Semaka et al , Kay et al ].
Limited data suggest that individuals with IAs may exhibit behavioral changes as well as motor and cognitive impairments, although more research is required in this regard [ Killoran et al , Cubo et al ]. A significant inverse correlation exists between the number of CAG repeats and the age of onset of HD [ Langbehn et al , Langbehn et al ]. See Molecular Genetics. For data on the age-specific likelihood of onset by trinucleotide repeat size, see cmmt.
In addition to age at clinical onset, CAG repeat length has also been shown to predict age at death, but not the duration of the illness [ Keum et al ]. The rate of deterioration of motor, cognitive, and functional measures increases with larger CAG repeat sizes [ Aziz et al , Chao et al ].
The progression of behavioral symptoms appears not to be related to repeat size [ Ravina et al ]. Homozygotes for fully penetrant HD alleles appear to have a similar age of onset to heterozygotes, but may exhibit an accelerated rate of disease progression [ Squitieri et al , Lee et al ]. Many genes at other loci have been shown to account for small amounts of this heritable portion of the variability [ Lee et al ]. Significant progress has been made in recent years in the identification of these additional genomic modifiers, both at the HTT locus and throughout the genome.
When this promoter variant is present on the normal HTT allele , it is associated with an earlier age of onset of HD, while an opposite effect is observed when the promoter variant is present on the HD-causing allele. Further, genome-wide association studies have begun to shed light on other candidate modifier genes for HD [ Lee et al , Moss et al ].
These analyses have shown the important role of biologic pathways involved in DNA repair, mitochondrial fission, and oxidoreductase activity with regard to this phenotype , and have identified candidate modifier genes for future study e. Alleles that contain 36 or more CAG repeats are considered HD-causing alleles and confer risk of developing the disease. Alleles that contain from 36 to 39 CAG repeats, however, are incompletely penetrant and may or may not result in HD.
Elderly asymptomatic individuals with CAG repeats in this range are common [ Kay et al ]. Alleles that contain more than 40 CAG repeats are completely penetrant. No asymptomatic elderly individuals with alleles of more than 40 CAG repeats have been reported. Anticipation, the phenomenon in which increasing disease severity or decreasing age of onset is observed in successive generations, is known to occur in HD. Anticipation occurs far more commonly in paternal transmission of the mutated allele. The phenomenon of anticipation arises from instability of the CAG repeat during spermatogenesis [ Semaka et al b ].
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Large expansions i. Most often children with juvenile-onset disease inherit the expanded allele from their fathers, although on occasion they inherit it from their mothers [ Nahhas et al ]. In the pre-molecular-genetic era, there were many different names for chorea, including St. Vitus's Dance and Sydenham's chorea.
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Individuals who do not yet show symptoms are in the premanifest phase of HD. HD prevalence varies dramatically across world regions. Populations of European ancestry display an average prevalence of 9. In contrast, HD appears much less frequently in Japan, China, Korea, and Finland, as well as in indigenous African populations from South Africa, with estimated prevalence values ranging from 0. Individuals living in the Lake Maracaibo region of Venezuela are believed to have the highest prevalence of HD in the world [ Wexler et al ].
The uneven distribution of HD is at least partially explained by the distribution of specific predisposing alleles and haplotypes in the general population of these ethnic groups [ Warby et al , Warby et al , Kay et al ]. For example, a recent study of 15 diverse global populations demonstrated that the mean CAG size in a population as well as intermediate allele frequency correlates with HD prevalence and contributes to differences in disease prevalence across major ancestry groups [ Kay et al ].
Reduced- penetrance HTT alleles see Establishing the Diagnosis , Allele sizes have recently been shown to occur at a high frequency in the general population, with as many as one in individuals carrying these alleles — although the penetrance rate was determined to be lower than previously reported i. Huntington disease HD falls into the differential diagnosis of chorea, dementia, and psychiatric disturbances. The differential diagnosis of several HD-like disorders is summarized here and reviewed elsewhere [ Schneider et al , Martino et al ].
The co-occurrence of Alzheimer disease and HD has also been reported [ Davis et al ]. Noninherited conditions are associated with chorea, but most can be excluded easily in an individual with suspected HD based on associated findings and the course of illness. Causes of chorea include tardive dyskinesia, levodopa-induced dyskinesia, thyrotoxicosis, cerebrovascular disease, cerebral lupus, polycythemia, and group A beta-hemolytic Streptococcus.
Inherited conditions. See Table 4. HDL1 is caused by a specific pathogenic variant 8 extra octapeptide repeats in the prion protein gene , PRNP , on chromosome 20p [ Laplanche et al , Moore et al ]. Similar pathogenic variants at this locus also result in other forms of prion disease such as familial Creutzfeldt-Jakob disease see Genetic Prion Diseases. The diagnosis of HD in children is straightforward in a family with a history of HD.
In simplex cases an affected individual with no known family history of HD , ataxia-telangiectasia , pantothenate kinase-associated neurodegeneration previously known as Hallervorden-Spatz syndrome , Lesch-Nyhan syndrome , Wilson disease , progressive myoclonic epilepsy [ Gambardella et al ], and other metabolic diseases must be excluded.
To establish the extent of disease and needs in an individual diagnosed with Huntington disease HD , the evaluations summarized in this section if not performed as part of the evaluation that led to the diagnosis are recommended:. Supportive care with attention to nursing, diet, special equipment, and eligibility for state and federal benefits is much appreciated by individuals with HD and their families. Numerous social problems beset individuals with HD and their families; practical help, emotional support, and counseling can provide relief [ Williams et al ].
The Behavior Observation Scale Huntington BOSH is a scale developed for the rapid and longitudinal assessment of functional abilities of persons with HD in a nursing home environment [ Timman et al ]. The total functional capacity TFC scale is used to describe the progression of HD, the level of functioning, and requirements for additional caregiver aid TFC scale. See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. Numerous human clinical trials are planned or under way for HD and are listed at www.
For the most up-to-date information see hddrugworks. Search ClinicalTrials. A number of candidate molecular biomarkers of disease onset and clinical progression have been assessed in HD patient cohorts, yet only a few have been validated. Mutated huntingtin levels in CSF have been shown to correlate with disease stage in HD [ Southwell et al , Wild et al ] and potentially reflect levels of mHTT in the brain [ Southwell et al ]. Moreover, levels of neurofilament light chain in blood and CSF have been shown to be a potential prognostic biomarker of disease onset and clinical progression as well as regional brain atrophy in individuals with HD [ Byrne et al , Johnson et al ].
Children and adolescents living with a parent affected with HD, sometimes in very deprived conditions, can have special problems. Referral to a local HD support group for educational material and needed psychological support is helpful see Resources. Donepezil , a drug used to treat Alzheimer disease, has not improved motor or cognitive function in HD [ Cubo et al ]. Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions.
The following section deals with genetic risk assessment and the use of family history and genetic testing to clarify genetic status for family members. This section is not meant to address all personal, cultural, or ethical issues that individuals may face or to substitute for consultation with a genetics professional. Huntington disease HD is inherited in an autosomal dominant manner. Sibs of a proband. The risk to the sibs of a proband depends on the genetic status of the proband's parent:. Other family members. The risk to other family members depends on the genetic status of the proband 's parents: if a parent is affected or has a CAG expansion in HTT , his or her family members are at risk.
Predictive testing i. Testing of asymptomatic adults at risk for HD is possible. Testing for the pathogenic variant in the absence of definite symptoms of the disease is predictive testing. Such testing is not useful in accurately predicting age of onset, severity, type of symptoms, or rate of progression in asymptomatic individuals.
However, data reported by Langbehn et al  and Langbehn et al  concerning the likelihood that an individual with a particular size of CAG repeat will be affected by a specific age may be useful. See Supplementary Tables at cmmt. Predictive testing in minors i. Considerations in families with an apparent de novo pathogenic variant. DNA banking is the storage of DNA typically extracted from white blood cells for possible future use. Because it is likely that testing methodology and our understanding of genes, allelic variants, and diseases will improve in the future, consideration should be given to banking DNA of affected individuals.
If the presence of an HD-causing HTT allele has been confirmed in the affected parent or in an affected relative of the at-risk parent, prenatal testing for a pregnancy at increased risk is possible. Preimplantation genetic diagnosis PGD may be an option for families in which an HD-causing HTT allele has been identified in an affected family member. Existing PGD exclusion protocols allow for testing of the embryo for couples in an at-risk family who do not wish to undergo presymptomatic testing for the HD-causing allele themselves [ Sermon et al , Stern et al , Moutou et al , Jasper et al ].
Differences in perspective may exist among medical professionals and within families regarding the use of prenatal testing when the testing is being considered for the purpose of pregnancy termination or for early diagnosis. While most centers would consider decisions regarding prenatal testing to be the choice of the parents, discussion of these issues is appropriate.
GeneReviews is not responsible for the information provided by other organizations. For information on selection criteria, click here. Gene structure. HTT is predominantly expressed as a Shorter transcripts have been reported to occur in some patients — resulting from alternative polyadenylation of the 3'UTR; although these transcripts are not present in transcript databases [ Lin et al , Romo et al ]. For a detailed summary of gene and protein information, see Table A , Gene. Benign variants. The CAG repeat length is highly polymorphic in the population and unaffected alleles have CAG repeat size ranges from nine to The median size allele is 18 CAGs.
The most common alleles in all populations contain repeats of CAGs in length [ Warby et al ]. Intermediate alleles range from 27 to 35 CAG repeats [ Semaka et al b ]. Pathogenic variants.
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Individuals with adult-onset HD usually have a CAG expansion from 40 to 55 whereas those with juvenile onset have CAG expansions greater than 60, often inherited from the father. A well-established inverse correlation between CAG repeat length and age of onset exists. However, penetrance of alleles with a CAG repeat range of is reduced. Note on variant classification: Variants listed in the table have been provided by the authors. GeneReviews staff have not independently verified the classification of variants.
See Quick Reference for an explanation of nomenclature. The first Gln-residue at position 18 is present in 23 copies; it is designated p. Normal gene product. Huntingtin is widely expressed with no obvious differences in the regional distribution of the mutated and wild type protein. The polyglutamine tract starts at residue 18 and is followed by a polyproline region. The region downstream of the polyglutamine tract contains a HEAT repeat, a motif consisting of 40 loosely conserved amino acids repeated multiple times in tandem, proposed to be involved in protein-protein interactions [ Palidwor et al ].
Abnormal gene product. The CAG repeat in HTT is translated into an uninterrupted stretch of glutamine residues that when expanded may have altered structural and biochemical properties. Booklets available through the Huntington Society of Canada :. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use. For questions regarding permissions or whether a specified use is allowed, contact: ude.
Turn recording back on. National Center for Biotechnology Information , U. GeneReviews by Title. Search term. GeneReviews Advanced Search Help. Huntington Disease Synonym: Huntington Chorea. Summary Clinical characteristics. Genetic counseling. Diagnosis Suggestive Findings Huntington disease HD should be suspected in individuals with any of the following: Progressive motor disability featuring chorea.
Voluntary movement may also be affected. Family history consistent with autosomal dominant inheritance. Establishing the Diagnosis The diagnosis of HD is confirmed in a proband with clinical signs and symptoms of HD by identification of a heterozygous expansion of a CAG trinucleotide repeat in HTT by molecular genetic testing see Table 1. Normal alleles. Intermediate alleles. An individual with an allele in this range is not at risk of developing symptoms of HD but, because of instability in the CAG tract, may be at risk of having a child with an allele in the HD-causing range [ Semaka et al ].
HD-causing alleles. Persons who have an HD-causing allele are considered at risk of developing HD in their lifetime. HD-causing alleles are further classified as:. Reduced- penetrance HD-causing alleles. An individual with an allele in this range is at risk for HD but may not develop symptoms. Full- penetrance HD-causing alleles.
Alleles of this size are associated with development of HD with increased certainty assuming a normal life span. Table 1. Clinical Characteristics Clinical Description During the prodromal phase of Huntington disease HD individuals may have subtle changes in motor skills, cognition, and personality Figure 1 [ Tabrizi et al , Ross et al , Liu et al ]. Figure 1. Table 2. Categories of Huntington Disease Diagnosis. Table 3. Intermediate alleles ranging from 27 to 35 CAG repeats usually do not confer the disease phenotype but are prone to CAG repeat instability [ Semaka et al c ].
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Penetrance Alleles that contain 36 or more CAG repeats are considered HD-causing alleles and confer risk of developing the disease. Anticipation Anticipation, the phenomenon in which increasing disease severity or decreasing age of onset is observed in successive generations, is known to occur in HD. Nomenclature In the pre-molecular-genetic era, there were many different names for chorea, including St. Prevalence HD prevalence varies dramatically across world regions.
Differential Diagnosis Huntington disease HD falls into the differential diagnosis of chorea, dementia, and psychiatric disturbances. Table 4. McLeod blood group phenotype. Management Evaluations Following Initial Diagnosis To establish the extent of disease and needs in an individual diagnosed with Huntington disease HD , the evaluations summarized in this section if not performed as part of the evaluation that led to the diagnosis are recommended: Physical examination.
Assessment of the full range of motor, cognitive, and psychiatric symptoms associated with HD. Among a range of clinical scoring systems that have been described, the Unified Huntington's Disease Rating Scale HDRS provides a reliable and consistent assessment of the clinical features and progression of HD. Tetrabenazine can be effective as an antichoreic drug; however, its use is associated with severe adverse effects such as extrapyramidal symptoms. Deutetrabenazine, a deuterated analog of tetrabenazine, has been modified by deuterium atom substitutions at specific sites on the molecule to increase half-life and systemic exposure [ Stamler et al ].
These properties allow for less frequent dosing with fewer adverse effects [ Huntington Study Group , Reilmann ]. Psychiatric disturbances such as depression, psychotic symptoms, and outbursts of aggression generally respond well to psychotropic drugs or some types of antiepileptic drugs. Valproic acid has improved myoclonic hyperkinesia in Huntington disease [ Saft et al ]. Prevention of Secondary Complications Significant secondary complications of HD include the following: The complications typically observed with any individual requiring long-term supportive care.
The side effects associated with various pharmacologic treatments. Drug side effects are dependent on a variety of factors including the compound involved, the dosage, and the individual; but with the medications typically used in HD, side effects may include depression, sedation, nausea, restlessness, headache, neutropenia, and tardive dyskinesia. For some individuals, the side effects of certain therapeutics may be worse than the symptoms; such individuals would benefit from being removed from the treatment, having the dose reduced, or being "rested" regularly from the treatment.
Current medications used to treat chorea are particularly prone to significant side effects. Individuals with mild to moderate chorea may be better assisted with non-pharmacologic therapies such as movement training and speech therapy. Standard treatment is appropriate when indicated [ Paulsen et al b , Phillips et al ]. Alcohol and smoking are discouraged. Evaluation of Relatives at Risk See Genetic Counseling for issues related to testing of at-risk relatives for genetic counseling purposes. Pharmacologic agents being investigated include inhibitors of: apoptosis, excitotoxicity, huntingtin aggregation, huntingtin proteolysis, huntingtin phosphorylation, inflammation, oxidative damage, phosphodiesterase activity, histone deacetylase, and transglutaminase activity; as well as compounds that modulate mitochondrial function, chaperone activity, transcription, and neurotrophic support.
Notably, many of these therapeutic agents have failed to meet clinical endpoints and demonstrate efficacy in modifying clinical progression of HD. Experimental therapeutics including pridopidine, laquinimod, and a semaphorin-4D neutralizing antibody are still in clinical development. Gene-silencing approaches to target the cause of HD have been shown to be safe and efficacious in preclinical animal studies and are currently undergoing or on the verge of entering clinical trials. These approaches aim to either silence all huntingtin expression in a nonselective manner [ Boudreau et al , McBride et al , Kordasiewicz et al ] or are allele -selective for only the mutated HTT allele [ Gagnon et al , Carroll et al , Evers et al , Skotte et al , Southwell et al , Datson et al ].
Allele selectivity can be achieved by targeting the expanded CAG tract [ Gagnon et al , Evers et al , Datson et al ] or by targeting polymorphisms in linkage disequilibrium with the CAG expansion [ Carroll et al , Skotte et al , Southwell et al , Kay et al ]. Moreover, the safety and efficacy of intravenously injected mesenchymal stem cells is currently being tested in a first-in-human clinical trial for individuals with HD NCT Of concern, recent studies suggest that mutated huntingtin is capable of spreading into the allografted neural tissue [ Cicchetti et al ].
Genetic Counseling Genetic counseling is the process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions. Mode of Inheritance Huntington disease HD is inherited in an autosomal dominant manner.
The family history of some individuals diagnosed with HD may appear to be negative for one of the following reasons:. Late onset of the disease in the affected parent. Molecular genetic testing is recommended for the parents of a proband who appears to represent a simplex case i. If the father has an intermediate HTT allele , the risk to the sibs of inheriting an HD-causing allele i.
Offspring of individuals with an intermediate allele are at risk for HD because the instability of the CAG repeat as it is passed between generations can result in CAG repeat expansion [ Semaka et al , Semaka et al b ]. Genetic counseling for individuals with intermediate alleles is particularly challenging because of the uncertain clinical outcome for their children [ Semaka et al a ]. The risk to a child of inheriting a CAG expansion greater than 35 repeats or a "new HD-causing allele" from a parent with an intermediate allele depends on a variety of factors, including the following:.
The CAG size of the allele. Larger CAG sizes are more prone to expansion. The sex and age of the transmitting parent. Paternally inherited intermediate alleles are more prone to CAG expansion than maternally inherited intermediate alleles; maternal expansions are extremely rare [ Semaka et al ]. Expanded intermediate alleles are preferentially transmitted by males with advanced paternal age. Related Genetic Counseling Issues Predictive testing i. At-risk asymptomatic adult family members may seek testing in order to make personal decisions regarding reproduction, financial matters, and career planning.
Asymptomatic individuals at risk may also be eligible to participate in clinical trials. Others may have different motivations including simply the "need to know. Those seeking testing should be counseled about problems they may encounter with regard to health, life, and disability insurance coverage, employment and educational discrimination, and changes in social and family interaction.
Interestingly, a study has found that genetic testing does not increase the risk for discrimination; perceived genetic discrimination is more likely due to the family history of HD regardless of gene status, rather than due to the specific results of the HD genetic test [ Bombard et al ]. Other issues to consider include implications for the at-risk status of other family members [ Bombard et al ].
Depression and suicide ideation are issues to be addressed as part of the predictive testing program for HD [ Robins Wahlin et al , Robins Wahlin ]. Informed consent should be obtained and records kept confidential. Individuals with a mutated allele need arrangements for long-term follow up and evaluations. Short-term follow up of the participants in the Canadian Predictive Testing Program has revealed that predictive testing for HD may maintain or even improve the psychological well-being of at-risk individuals even though some had negative experiences. The major issue for these individuals is the realization that they are facing an unplanned future.
Overall, the demand for testing of at-risk asymptomatic adults has been lower than expected in studies conducted before the availability of direct molecular genetic testing. Consistent with use of medical services and genetic testing in general, women are more likely than men to undergo predictive testing for HD [ Taylor , Baig et al ].
In their study of psychological distress in the partners of asymptomatic individuals who had inherited an HD-causing allele , Decruyenaere et al  found that partners have at least as much distress as the individuals found to have the HD-causing allele yet their grief tends to be "disenfranchised" or not socially recognized.
For asymptomatic minors at risk for adult-onset conditions for which early treatment would have no beneficial effect on disease morbidity and mortality, predictive genetic testing is considered inappropriate, primarily because it negates the autonomy of the child with no compelling benefit. Further, concern exists regarding the potential unhealthy adverse effects that such information may have on family dynamics, the risk of discrimination and stigmatization in the future, and the anxiety that such information may cause. For more information, see the National Society of Genetic Counselors position statement on genetic testing of minors for adult-onset conditions and the American Academy of Pediatrics and American College of Medical Genetics and Genomics policy statement : ethical and policy issues in genetic testing and screening of children.
In a family with an established diagnosis of HD, it is appropriate to consider testing of symptomatic individuals regardless of age. The optimal time for determination of genetic risk and discussion of the availability of prenatal testing is before pregnancy. Similarly, decisions about testing to determine the genetic status of at-risk asymptomatic family members are best made before pregnancy. Huntington disease. EHDN Registry. Table A. Huntington Disease: Genes and Databases. Table B. Table 5. Laboratory guidelines for Huntington disease genetic testing.
Am J Hum Genet. Ethical and policy issues in genetic testing and screening of children. Available online. Accessed Guidelines for the molecular genetics predictive test in Huntington's disease. Guidelines for the molecular genetic predictive test in Huntington's disease. National Society of Genetic Counselors. Position statement on genetic testing of minors for adult-onset conditions.
Ethical issues policy statement on Huntington's chorea molecular genetics predictive test. J Neurol Sci. Behavioral symptoms associated with Huntington's disease. Adv Neurol. Aronin N, DiFiglia M. Huntingtin-lowering strategies in Huntington's disease: antisense oligonucleotides, small RNAs, and gene editing. Mov Disord. Inclusion body formation reduces levels of mutant huntingtin and the risk of neuronal death. Asscher E, Koops B-J.
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The right not to know and preimplantation genetic diagnosis for Huntington's disease. J Med Ethics. Normal and mutant HTT interact to affect clinical severity and progression in Huntington disease. Effect of fetal neural transplants in patients with Huntington's disease 6 years after surgery: a long-term follow-up study. Lancet Neurol. Quarrell OW. Eur J Hum Genet. Suicide in Hungarian Huntington's disease patients. The long-term safety and efficacy of bilateral transplantation of human fetal striatal tissue in patients with mild to moderate Huntington's disease.
J Neurol Neurosurg Psychiatry. Nat Rev Dis Primers. Bean L, Bayrak-Toydemir P. Genet Med. Nat Neurosci. Creatine supplementation lowers brain glutamate levels in Huntington's disease. J Neurol. Proceed with care: direct predictive testing for Huntington disease. A novel pathogenic pathway of immune activation detectable before clinical onset in Huntington's disease.
J Exp Med. Saccades in presymptomatic and early stages of Huntington disease. Beyond the patient: the broader impact of genetic discrimination among individuals at risk of Huntington disease. Perceptions of genetic discrimination among people at risk for Huntington's disease: a cross sectional survey. Bonelli RM, Hofmann P. A systematic review of the treatment studies in Huntington's disease since Expert Opin Pharmacother. Pharmacological management of Huntington's disease: an evidence-based review.
Curr Pharm Des. Huntington's disease: present treatments and future therapeutic modalities. Int Clin Psychopharmacol. Huntington's disease: from huntingtin function and dysfunction to therapeutic strategies. Cell Mol Life Sci. Nonallele-specific silencing of mutant and wild-type huntingtin demonstrates therapeutic efficacy in Huntington's disease mice.
Mol Ther. Cognitive impairment and behavioural difficulties in patients with Huntington's disease. Nurs Stand. Neurofilament light protein in blood as a potential biomarker of neurodegeneration in Huntington's disease: a retrospective cohort analysis. Risk factors for the onset and progression of Huntington disease. Mutant huntingtin is present in neuronal grafts in Huntington disease patients.
Ann Neurol. Clinical manifestations of intermediate allele carriers in Huntington disease. Effect of donepezil on motor and cognitive function in Huntington disease. PLoS One. The co-occurrence of Alzheimer's disease and Huntington's disease: a neuropathological study of 15 elderly Huntington's disease subjects. J Huntingtons Dis. Efficacy of levetiracetam in Huntington disease. Clin Neuropharmacol. Partners of mutation-carriers for Huntington's disease: forgotten persons?
Weight loss in early stage of Huntington's disease. Metabolism in HD: still a relevant mechanism? Psychiatric symptoms in Huntington's disease before diagnosis: the predict-HD study. Biol Psychiatry. Stem cell transplantation for Huntington's disease. Exp Neurol. Changes in mental state and behaviour in Huntington's disease. Lancet Psychiatry. Longitudinal psychiatric symptoms in prodromal Huntington's disease: a decade of data. Am J Psychiatry.
Targeting several CAG expansion diseases by a single antisense oligonucleotide. Neural transplantation in Huntington's disease: the NEST-UK donor tissue microbiological screening program and review of the literature. Cell Transplant. Multisource ascertainment of Huntington disease in Canada: prevalence and population at risk. Positron emission tomography after fetal transplantation in Huntington's disease.
Energy balance in early-stage Huntington disease. Am J Clin Nutr. Allele-selective inhibition of mutant huntingtin expression with antisense oligonucleotides targeting the expanded CAG repeat. Functional differences between direct and indirect striatal output pathways in Huntington's disease. Details if other :. Thanks for telling us about the problem. Return to Book Page. Blasingame Jr. In this book, young adult literature expert Jim Blasingame helps teachers understand the power and purpose of young adult literature.
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Sort order. Mar 07, E. Martin rated it really liked it. I teach at-risk high school kids who pretty much hate reading, so I'm constantly looking for books they might be interested in. Not only did this book give me direct suggestions, but it offered tips on how to find others. Definitely a must-read for anyone working with teens. Apr 27, Sara Weinhold rated it liked it. Not as useful as I had hoped - book lists by genre ok. Author repeated books frequently. May 11, Carol rated it it was amazing. I like this book for reference, but I'm ready for the "new and newer" version.
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