INTRODUCTION — Huntington disease (HD) is an inherited progressive neurodegenerative disorder characterized by choreiform movements, psychiatric problems, and dementia. It is caused by a cytosine-adenine-guanine (CAG) trinucleotide repeat expansion in the huntingtin (HTT) gene on chromosome 4p and inherited in an autosomal dominant pattern. The pathophysiology of HD is not fully understood, although it is thought to be related to toxicity of the mutant huntingtin protein. As there is no known cure, treatment is symptomatic and remains supportive.
This topic will review the clinical features and diagnosis of HD. Other aspects of HD are discussed separately. (See "Huntington disease: Genetics and pathogenesis" and "Huntington disease: Management".)
ETIOLOGY AND GENETICS — The genetics and pathogenesis of HD are reviewed here briefly and discussed in detail separately. (See "Huntington disease: Genetics and pathogenesis".)
HD is an autosomal dominant disorder caused by an expansion of the cytosine-adenine-guanine (CAG) trinucleotide in the HTT gene (also known as the HD gene) that encodes the protein huntingtin, resulting in an expanded polyglutamine tract. Huntingtin is present in a large number of tissues throughout the body. However, pathology mainly involves the central nervous system, with atrophy of the caudate and putamen (the neostriatum) being most prominent. At the cellular level, protein aggregates are seen in both the cytoplasm and the nucleus. The pathophysiology of neuron loss is incompletely understood. The huntingtin protein is thought to become toxic with the CAG expansion ("gain of function") but continues to serve a function that is critical to survival in early development.
The main determinant of age of onset is the number of CAG repeats in the HTT gene. The normal number of repeats is 26 or less. Repeats between 27 and 35 will not develop symptoms, but the next generation is at a small risk to develop expansion, which may or may not be into the disease-causing range. Repeats between 36 and 39 are incompletely penetrant; individuals may develop symptoms but typically with a late age of onset. When repeats are equal to or greater than 40, the disease is fully penetrant and symptoms of the disease will occur. Those individuals with the earliest onset tend to have the largest expansion in the number of repeats, while onset late in life correlates with a lower expansion of the repeat number. Rate of disease progression is also inversely related to repeat size. Additional factors predicting age of onset are thought to be environmental and/or due to other genetic determinants.
As with all trinucleotide disorders, there is genetic instability. Expansion of the repeat number between successive generations, which causes an earlier and more severe phenotype, is termed "anticipation." Paternal inheritance results in the largest increase. Thus, children with juvenile-onset HD will have typically inherited the pathological allele with expansion from the father. (See "Huntington disease: Genetics and pathogenesis", section on 'Anticipation and transmitting parent effect'.)
EPIDEMIOLOGY — A 2012 meta-analysis that evaluated HD epidemiology studies published since 1985 made the following observations [1]:
●The worldwide prevalence of HD was 2.7 cases per 100,000 persons
•In studies from Europe, North America, and Australia, the prevalence of HD was 5.7 cases per 100,000 persons
•In studies from Asia, the prevalence of HD was 0.4 cases per 100,000 persons
●The worldwide incidence of HD was 0.38 cases per 100,000 persons per year
The differences in prevalence among ethnic populations are reflected in the size of the normal allele in the population (ie, in European countries, the normal cytosine-adenine-guanine [CAG] repeat size is higher than that found in Asian countries) [2].
Age of onset ranges from childhood to the eighth decade, but is most common in mid-life. Diagnosis before 20 years of age is considered juvenile HD, or the Westphal variant of HD, and comprises less than 10 percent of cases [3-6]. (See "Bradykinetic movement disorders in children", section on 'Juvenile Huntington disease'.)
CLINICAL FEATURES — Clinically, HD is characterized by chorea, psychiatric illness, and dementia (table 1). Symptoms begin insidiously with movement abnormalities and/or with psychiatric and cognitive features. Motor presentations become increasingly common with advancing age [7]. The course is one of slow but relentless deterioration in cognitive and motor function.
Motor symptoms and signs — Chorea is a key feature of HD, and the defining symptom at the time of diagnosis. Chorea is characterized by brief, abrupt, involuntary, nonstereotyped movements involving the face, trunk, and limbs [8]. Initially, the movements are mild and may be misinterpreted as restlessness. Patients may be unaware of the movements and incorporate the chorea into purposeful actions, a phenomenon termed "parakinesia." In a longitudinal study of HD mutation carriers, nearly one-half of patients with onset of unequivocal motor signs of HD were unaware of motor symptoms [9].
Hypotonia with hyperreflexia is a feature of early disease. Dystonia (prolonged, sustained, abnormal postures) may be seen in the hands with such activities as walking. Mild bradykinesia is also observed.
Progressive loss of voluntary motor control is a characteristic feature of HD [10]. Gradually, the chorea becomes more florid and widespread, interfering with movement. In later stages, chorea also affects the diaphragm, pharynx, and larynx, producing dysarthria, dysphagia, and involuntary vocalizations.
Motor impersistence (the inability to sustain certain simple voluntary acts) is another common manifestation of HD. As an example, patients may have difficulty with sustained tongue protrusion.
With disease progression, motor function slowly deteriorates, and chorea may eventually be replaced by a parkinsonian akinetic-rigid state in the advanced stages. Walking becomes unsafe when chorea and parkinsonism prevent adequate compensation.
Eye movements — Abnormal eye movements can be a prominent finding in HD, particularly in younger adult patients. In patients with early HD, there is delay in the initiation of volitional saccades (quick conjugate eye movements between points of fixation), and saccade velocity is reduced [11-13]. This is characterized by the absence of saccadic movement with preservation of smooth pursuit. Optokinetic nystagmus is abnormal in very early stages. In more advanced stages of HD, smooth pursuit, voluntary saccades, and refixation are all impaired [14,15].
Psychiatric symptoms — Patients with HD may present with irritability, depression, and/or disrupted social relationships up to several years prior to onset of chorea [16-18]. Depression, paranoia, delusions, and hallucinations can develop at any point in the illness [19]. HD is associated with an increased risk of suicide for diagnosed patients and at-risk family members. The suicide rate of affected individuals is 7 percent [20], while rates of suicidal ideation among HD mutation carriers are as high as 20 percent [21,22]. Risk factors for suicidality in patients with HD include depression, anxiety, and substance use [21-23].
The prevalence of depressed mood, irritability, apathy, and anxiety in patients with HD ranges from 33 to 76 percent [24]. Less frequent symptoms include obsessive-compulsive behavior (10 to 52 percent) and psychosis (3 to 11 percent). Psychiatric symptoms do not correlate with duration of disease, repeat length, or presence of dementia or motor symptoms [25-27].
Cognitive impairment and dementia — Cognitive decline is inevitable in HD. Rarely, patients with onset of HD late in life may have motor symptoms only, presumably because the remaining life span is too short for cognitive symptoms to become obvious.
The dominant cognitive feature of HD is executive dysfunction with diminished ability to make decisions, multitask, and switch from one set of cognitive goals to another. Patients typically lack insight into their cognitive deficits and may be unaware of their perceptual, motor, and psychiatric problems related to HD [28].
The dementia of HD, like other non-Alzheimer dementias, has been described in the older literature as subcortical, referring to clinical models of cognition that highlight frontostriatal pathways as facilitators of speed and efficiency of thought.
On formal testing, patients with HD find time-based tasks particularly difficult; examples include word fluency, picture sequencing, and the Wisconsin card sorting test [29]. When compared with patients who have Alzheimer disease, a type of cortical dementia, patients with HD display greater improvement with cuing during recall tasks [30]. This implies that the difficulty in HD is due to an inefficient search of memory. Despite evidence of cognitive abnormalities early in HD [31], memory loss is usually a late finding [17]. Difficulties with other typically cortical functions, such as aphasia and apraxia, are uncommon.
Weight loss and cachexia — Weight loss and cachexia are common features of HD, despite efforts to maintain appropriate caloric intake.
The pathophysiology of weight loss is not well understood [32]. Possible contributors include energy expenditure due to hyperkinetic movements and altered cellular metabolism in muscle or adipose tissue [33,34]. Some evidence suggests that weight loss correlates with a higher cytosine-adenine-guanine (CAG) repeat number in mutant HTT [35].
Atypical features — Rarely, adult-onset cases present with either cerebellar-type limb and gait ataxia, myoclonus, seizures, or generalized dystonia [36-38]. These presentations tend to occur in patients with a younger age of onset (ie, late adolescence or early adulthood). Older adult patients can sometimes present with signs of parkinsonism without tremor.
Juvenile Huntington disease — When HD presents before age 20, clinical features can include myoclonus, seizures, behavioral problems, and parkinsonism. Compared with adults, children presenting with HD are more likely to have prominent psychiatric and/or cognitive features at the time of disease onset [7]. Chorea is notably absent (table 2). (See "Bradykinetic movement disorders in children", section on 'Juvenile Huntington disease'.)
Prediagnosis manifestations — The following observations suggest that mutant HTT causes subtle manifestations long before the overt symptoms of HD are recognized:
●Using quantitative neuropsychologic tests, neurologic examination, and brain imaging, small but statistically significant differences have been reported between asymptomatic HD cases and controls [39-49]. Abnormalities have been found in psychomotor speed, negative emotion recognition, irritability, optokinetic nystagmus, motor performance (eg, rapid alternating hand movements, timing of finger taps), and whole brain volume.
●Data from studies employing magnetic resonance imaging (MRI) and positron emission tomography (PET) have shown initial striatal hypertrophy, then atrophy and hypometabolism predating any clinical features by up to 30 years in asymptomatic patients with HD [50-52]. These structural and metabolic changes may explain the early symptoms of HD and could serve as a biomarker to identify presymptomatic patients who may benefit from therapeutic intervention [53].
●A case-control study found that asymptomatic children who were at risk for HD due to CAG repeat expansion length ≥39 in the HTT gene had small but statistically significant reductions in mean head circumference, body mass index, weight, and height compared with healthy controls [54].
Despite these findings, surveys based on analysis of friends and families of patients with HD indicate that the motor disorder is their first indication of disease [16,17].
Defining the first symptoms or signs of HD has been the focus of a number of studies of at-risk and asymptomatic patients with HD. Understanding this stage of the illness may allow future therapeutic trials of neuroprotection to focus on delaying clinical onset in those shown to have the HTT mutation. A staging framework, which incorporates genetic data (number of CAG repeats), preclinical biomarkers (eg, putamen and caudate volume), early cognitive and motor signs and symptoms, and functional changes, has been proposed to help standardize research efforts and aid in clinical trial design [53].
Neuroimaging — Axial MRI through the lateral ventricles demonstrates caudate atrophy, defined by the loss of the normal protrusion of the caudate head into the lateral ventricle in late-stage HD (image 1). Caudate atrophy, quantified by simple analysis of linear caudate measurements, correlates with change in cognitive function [55]. Functional imaging using PET and MRI also shows abnormal metabolic changes in the caudate [51,56,57].
Using computational MRI methods, progressive regional thinning of the cerebral cortex has been reported in patients with both preclinical and symptomatic HD [58-60]. These cortical changes may underlie some of the clinical heterogeneity of the disease.
CLINICAL PROGRESSION — Regardless of age of onset, HD is a chronic, slowly progressive disease [61]. The average length of survival after clinical onset ranges from 10 to 20 years, and some affected individuals live for 30 to 40 years [62]. Although progression occurs gradually along a continuum, HD can be divided into individual stages that encapsulate the expected clinical course.
Early stage — Patients in the early stage of HD are generally functional and independent with most activities of daily living, often remaining independent and able to work and drive [62]. However, symptoms of HD are present, such as slight involuntary movements, mild incoordination, difficulty with complex mental tasks, and some degree of irritability, disinhibition, or depression. Slowed voluntary eye movements can be seen, particularly in younger individuals.
Middle stage — Patients in the middle stage of HD begin to lose the ability to work, drive, or manage their own affairs without assistance [62]. In most cases, they will require some assistance with eating, dressing, and personal care. Cognitive decline worsens with diminished ability to solve problems. There is usually increased chorea and difficulty with voluntary motor movements. Impairments in walking and balance may lead to falls. Other problems may include swallowing dysfunction and weight loss.
Late stage — The slow but relentless deterioration in cognitive and motor function causes significant morbidity and early mortality. Patients in the late stage of HD require round-the-clock supervision and care in all activities of daily living [62,63]. The loss of voluntary motor control worsens; the few remaining voluntary movements are often ballistic and high amplitude, which may cause injury due to falls or limb trauma. Most become bedridden. Dysphagia may require placement of a feeding tube to maintain adequate nutrition. Although often nonverbal, patients in the late stage of HD may retain some comprehension.
While sharing the need for 24-hour care, patients with late-stage HD can differ dramatically in disease expression [63]. As examples, some have prominent, severe behavioral disturbances, some have severe chorea and gait disturbance without significant behavioral involvement, and others have severe unawareness of symptoms.
The advance stage of HD can last for a decade or longer, depending on the level of care [63]. Complications of immobility, such as aspiration pneumonia and other infections, result in death 10 to 40 years after disease onset [64].
EVALUATION AND DIAGNOSIS — The diagnosis of HD is based upon presence of the typical clinical features, a family history of the disease (if known), and genetic confirmation of the expansion. Genetic testing for HD involves targeted mutation analysis for pathogenic expansion of the HTT gene. With the availability of genetic molecular testing, all suspected HD cases can be easily confirmed. Molecular testing can also help avoid unnecessary investigations.
In the era of molecular testing, neuroimaging is no longer used in confirming the diagnosis of HD. Nevertheless, neuroimaging studies are generally used to rule out other structural disorders. (See 'Neuroimaging' above.)
Family history — A family history of genetically proven HD is a key factor in the diagnosis. Siblings or children of an index case who present with symptoms typical of HD can be confidently diagnosed based on a detailed history and physical examination. A careful review of the family history may reveal misdiagnosed parents or grandparents with psychiatric illness and/or suicide.
There is no apparent family history in up to 8 percent of patients with genetically proven HD [65,66]. This finding may be due to misdiagnosis in a family member, death of the affected parent prior to onset or recognition of symptoms, or unknown family history due to adoption. Occasionally, there is no family history of HD because the disease is caused by a new HTT gene expansion in the affected individual.
Genetic testing — In a patient with clinical features that raise suspicion for the disorder, the diagnosis of HD is confirmed by a targeted mutation analysis finding of a cytosine-adenine-guanine (CAG) trinucleotide expansion of ≥36 repeats in the HTT gene. Genetic testing is sensitive (98.8 percent) and specific (100 percent) for HD [67]. It allows for easy confirmation of clinical diagnosis as well as diagnosis of atypical patients.
For those without a family history, genetic confirmation of HD has significant consequences for other at-risk family members. Reproductive decision-making and implications to children of the index case also need special management. Everyone should have genetic counseling before the decision is made to go forward with testing.
While any treating clinician can appropriately request molecular confirmation of a clinical diagnosis, predictive testing (ie, testing at-risk asymptomatic individuals to see whether they carry the gene) should only be done in a specialized setting, such as a genetics clinic, with detailed counseling and a multidisciplinary team consisting of neurologists, psychiatrists, and genetic counselors. (See 'Predictive (presymptomatic) genetic screening' below.)
Who should be tested? — Diagnostic genetic testing for HD is indicated for symptomatic adult patients with unequivocal motor signs of HD, with or without a family history of HD [68].
Diagnostic genetic testing may also be indicated for children with a positive family history of HD who develop features consistent with juvenile-onset HD (eg, children with two or more of the following: declining school performance, seizures, oral motor dysfunction, rigidity, and gait disturbance) [69]. To avoid erroneous assignment of symptoms to HD and premature genetic testing, some experts recommend that a neurologist evaluate the child twice at intervals 6 to 12 months apart [70]. If the neurologic evaluations confirm persistent or progressive symptoms attributable to HD, genetic testing for HD would be appropriate. (See "Bradykinetic movement disorders in children", section on 'Juvenile Huntington disease'.)
Predictive genetic testing is an option for individuals who are at risk for developing HD, a category that includes asymptomatic individuals with a positive family history of HD and patients with a positive family history who have prodromal symptoms (eg, irritability, anxiety, depression, or cognitive impairment) that suggest the impending onset of symptomatic HD. Pretest genetic counseling is recommended before pursuing predictive genetic testing. (See 'Predictive (presymptomatic) genetic screening' below.)
Repeat expansion in HTT absent — In different studies evaluating patients with a typical HD phenotype, genetic testing for pathological CAG repeat expansions in HTT is negative in 1 to 12 percent [67,71,72]. In such cases, several genetically heterogeneous disorders that are phenotypically similar to HD (ie, HD phenocopy syndromes) should be considered, such as neurodegenerative disease caused by repeat expansions in the C9orf72 gene, dentatorubral pallidoluysian atrophy (DRPLA), HD-like 2 (HDL2), spinocerebellar ataxia type 17, familial prion disease, and Friedreich ataxia [73]. C9orf72 appears to be the most frequent cause of HD phenocopy syndromes. These disorders are discussed below. (See 'Hereditary disorders and HD phenocopy syndromes' below.)
Therefore, in a patient with suspected HD (eg, presenting with chorea or dementia, with or without a family history) where the HTT gene test is negative, genetic testing for repeat expansions in the C9orf72 gene should be obtained as the next step, followed by testing for spinocerebellar ataxia type 17 (algorithm 1). Evaluation for additional causes of HD mimics should be directed by individual clinical characteristics.
The yield of further genetic screening in such patients is low. This point is illustrated by the findings from a case series of 285 patients with clinical syndromes consistent with HD who were negative for the CAG repeat expansion in the HTT gene [74]. Additional screening for mutations associated with hereditary disorders that phenotypically resemble HD confirmed a genetic diagnosis in eight patients (3 percent), including seven with one of the HD-like syndromes and one with Friedreich ataxia.
Predictive (presymptomatic) genetic screening — In our clinical experience, approximately 15 percent of asymptomatic individuals with a family history of HD wish to undergo testing to determine whether they carry the disease-causing HTT repeat expansion. Common reasons for requesting testing include making decisions for child bearing, career and educational choices, or retirement planning.
Presymptomatic testing should only be performed by specialists at a multidisciplinary clinic where pretest guidance, test interpretation, and posttest psychological support can be provided regardless of test outcome. Patients should be informed that genetic testing does not allow one to determine the age of onset or other clinical factors because of the variability inherent in HTT gene expression. In addition, it should be noted that predictive genetic testing is associated with a risk of adverse psychosocial effects related to the patient's mood, self-perception, family and social relationships, and insurability [75].
The combined risk of suicide, attempted suicide, and psychiatric hospitalization after predictive testing for HD is approximately 1 percent with appropriate support [76]. The risk is highest for those who are unemployed or have a prior psychiatric history. Persons who test negative for HD are also at an increased risk of depression.
In patients who carry the disease-causing CAG expansion in the HTT gene, prenatal testing is available [77], although rarely used. Prenatal testing is only done in situations where the mother would consider termination of the pregnancy should the fetus test positive. Otherwise, prenatal testing is the same as testing an asymptomatic child, which is not recommended.
Despite increased understanding of the causes of age of onset, we do not recommend the use of family history or determination of CAG repeat length to make clinical predictions for individual patients, as these indicators are not sufficiently accurate for this purpose [3], particularly at the lower repeat sizes. This point is illustrated by finding that the time of disease onset for one pair of monozygotic twins differed by more than seven years [78]. A more complete understanding of influences on HD expression may allow us to predict age of onset more reliably in the future.
DIFFERENTIAL DIAGNOSIS — For a patient with chorea who is atypical for HD or is negative for the cytosine-adenine-guanine (CAG) repeat expansion in HTT, the differential diagnosis is broad and consists of hereditary (table 3) and acquired causes (table 4 and table 5). (See "Overview of chorea".)
Brain magnetic resonance imaging (MRI) can be useful in identifying an alternative diagnosis, such as ischemic infarction, pantothenate kinase-associated neurodegeneration, multiple sclerosis, neoplasm, or Creutzfeldt-Jakob disease.
Hereditary disorders and HD phenocopy syndromes — Hereditary causes of chorea range from benign familial chorea to degenerative disorders. Genetically heterogeneous disorders that are phenotypically similar to HD (ie, HD phenocopy syndromes) include neurodegenerative disease caused by repeat expansions in the C9orf72 gene, dentatorubral pallidoluysian atrophy (DRPLA), HD-like 2 (HDL2), spinocerebellar ataxia type 17, familial prion disease, and Friedreich ataxia (algorithm 1) [73,79]. C9orf72 appears to be the most frequent cause of HD phenocopy syndromes.
●Benign hereditary chorea is a nonprogressive condition, with onset in infancy or early childhood. Hypotonia and mild developmental delay can be seen. The symptoms typically improve with age, and the condition is not associated with dementia. (See "Hyperkinetic movement disorders in children", section on 'Childhood-onset hereditary chorea'.)
●Neurodegenerative disease caused by hexanucleotide repeat expansions in the C9orf72 gene can present as an HD phenocopy. In a cohort of 514 patients with suspected HD in whom genetic testing for HTT was negative, repeat expansions in the C9orf72 gene were identified in 10 (2 percent), making it the most common genetic cause of HD phenocopy syndromes [80]. Incomplete penetrance of C9orf72 expansions can occur, which can confound the family history.
Mutations in the C9orf72 gene involving the repeat expansion are the most common cause of familial frontotemporal dementia (FTD) and familial amyotrophic lateral sclerosis (ALS), and have been identified in some sporadic cases of FTD, ALS, and parkinsonism. (See "Familial amyotrophic lateral sclerosis", section on 'C9ORF72 gene' and "Epidemiology and pathogenesis of amyotrophic lateral sclerosis", section on 'Genetic susceptibility in sporadic ALS' and "Frontotemporal dementia: Epidemiology, pathology, and pathogenesis", section on 'C9orf72 expansion'.)
●Huntington disease-like 2 (HDL2) is a rare HD mimic caused by a trinucleotide expansion (CAG/cytosine-thymine-guanine [CTG]) in the junctophilin 3 (JPH3) gene on chromosome 16q24.3 [81]. It has been reported mainly but not exclusively in individuals from Africa [82,83]. Some of the cases of HDL2 have acanthocytosis. (See "Neuroacanthocytosis", section on 'Huntington disease-like 2'.)
●Occasionally, the spinocerebellar ataxias (eg, SCA types 1, 3, and 17) may present with an HD-like phenotype [84]. (See "The spinocerebellar ataxias".)
●Dentatorubral pallidoluysian atrophy (DRPLA) is a rare autosomal dominant disorder that typically presents in patients from Japan with chorea, ataxia, and dementia. A variant of DRPLA, known as the Haw-River syndrome, has been reported in an African American family. (See "The spinocerebellar ataxias", section on 'Dentatorubral pallidoluysian atrophy'.)
●Pantothenate kinase-associated neurodegeneration is a form of neurodegeneration with brain iron accumulation that typically presents with dystonia and basal ganglia iron deposition in children. It is an autosomal recessive disorder caused by mutations in the gene encoding pantothenate kinase 2. (See "Bradykinetic movement disorders in children", section on 'Neurodegeneration with brain iron accumulation'.)
●Neuroferritinopathy, another form of neurodegeneration with brain iron accumulation, is an autosomal dominant basal ganglia disease characterized by adult onset of variable symptoms that include parkinsonism, chorea, and dystonia [85]. The disorder is caused by mutations in the ferritin light chain gene.
●Neuroacanthocytosis is a group of disorders that can produce chorea and dementia. These features are accompanied by acanthocytes on peripheral blood smear. Additional manifestations may include neuropathy, seizures, self-mutilation, and oral-buccal-lingual dystonic movements. (See "Neuroacanthocytosis".)
●Friedreich ataxia is an autosomal recessive neurodegenerative disorder caused by mutations in the frataxin gene. The major clinical manifestations are neurologic dysfunction, cardiomyopathy, and diabetes mellitus. Almost all patients present with ataxia, and dysarthria is a common feature. (See "Friedreich ataxia".)
Of these hereditary diseases, neurodegenerative disease due to C9orf72 gene hexanucleotide expansions, DRPLA, and HDL2 in particular can be phenotypically indistinguishable from HD [80,86]. Genetic testing is available for most of these phenocopies.
Acquired disorders — Acquired causes of chorea include the following:
●Drug and toxic exposure.
●Tardive dyskinesia, which is associated with drugs that block dopamine receptors (eg, antipsychotics and metoclopramide). Tardive dyskinesia tends to occur months or years after the initiation of treatment. (See "Tardive dyskinesia: Etiology, risk factors, clinical features, and diagnosis".)
●Sydenham chorea, which is associated with a history of rheumatic fever or streptococcal infection in childhood. (See "Sydenham chorea".)
●Creutzfeldt-Jakob disease, which is a rapidly progressive dementing illness associated with ataxia and myoclonus. (See "Creutzfeldt-Jakob disease".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Huntington disease".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Huntington disease (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Overview – Huntington disease (HD) is an inherited progressive neurodegenerative disorder characterized by choreiform movements, psychiatric problems, and dementia. (See 'Introduction' above.)
●Epidemiology – The estimated prevalence of HD is 5 to 8 per 100,000 population in Europe and North America, with a lower prevalence in non-European ethnic groups. (See 'Epidemiology' above.)
●Clinical features – Symptoms of HD begin insidiously with movement abnormalities and/or with psychiatric and cognitive features. Chorea is a key feature of HD, and the defining sign at the time of diagnosis. Psychiatric problems can include irritability, depression, dysphoria, agitation, apathy, anxiety, paranoia, delusions, and hallucinations. The dementia of HD is characterized by executive dysfunction. (See 'Clinical features' above.)
With disease progression, motor function slowly deteriorates. Chorea may eventually be replaced in advanced stages of HD by a parkinsonian akinetic-rigid state. The slow but relentless deterioration in cognitive and motor function causes significant morbidity and early mortality. (See 'Late stage' above.)
●Neuroimaging – Axial magnetic resonance imaging (MRI) through the lateral ventricles demonstrates typical and prominent findings of caudate atrophy in late-stage HD. (See 'Neuroimaging' above.)
●Diagnosis – The diagnosis of HD is based upon the presence of the typical clinical features, a family history of the disease, and confirmatory genetic testing for the disease-causing trinucleotide (cytosine-adenine-guanine [CAG]) repeat expansion in the huntingtin (HTT) gene. However, there is no apparent family history in up to 8 percent of patients with genetically proven HD. Approximately 1 percent of patients with a typical HD phenotype test negative for the HTT gene repeat expansion. (See 'Evaluation and diagnosis' above.)
●Genetic testing – Diagnostic genetic testing for HD is indicated for symptomatic adult patients with unequivocal motor signs of HD and may be appropriate for children with a positive family history of HD and persistent or progressive features consistent with juvenile HD. Predictive genetic testing is an option for individuals who are at risk for developing HD, a category that includes asymptomatic individuals with a positive family history of HD. (See 'Who should be tested?' above.)
●Differential diagnosis – The differential diagnosis for HD is broad and includes hereditary (table 3) and acquired (table 4 and table 5) causes of chorea. Among the hereditary diseases, neurodegenerative disease due to C9orf72 gene hexanucleotide expansions, dentatorubral pallidoluysian atrophy (DRPLA), and HD-like 2 (HDL2) can be phenotypically indistinguishable from HD. (See 'Differential diagnosis' above.)
