Diagnosis of the onset of<unk>  can be made following the appearance of physical symptoms specific to the disease. Genetic testing can be used to confirm a physical diagnosis if no family history of<unk>  exists. Even before the onset of symptoms, genetic testing can confirm if an individual or embryo carries an expanded copy of the trinucleotide repeat (CAG) in the HTT gene that causes the disease. Genetic counseling is available to provide advice and guidance throughout the testing procedure and on the implications of a confirmed diagnosis. These implications include the impact on an individual's psychology, career, family-planning decisions, relatives, and relationships. Despite the availability of presymptomatic testing, only 5% of those at risk of inheriting<unk>  choose to do so. Clinical Coronal section from an MR brain scan of a patient with<unk> , showing atrophy of the heads of the caudate nuclei, enlargement of the frontal horns of the lateral ventricles (hydrocephalus ex vacuo), and generalized cortical atrophy A physical examination, sometimes combined with a psychological examination, can determine whether the onset of the disease has begun. Excessive unintentional movements of any part of the body are often the reason for seeking medical consultation. If these are abrupt and have random timing and distribution, they suggest a diagnosis of<unk> . Cognitive or behavioral symptoms are rarely the first symptoms diagnosed; they are usually only recognized in hindsight or when they develop further. How far the disease has progressed can be measured using the unified<unk>  rating scale, which provides an overall rating system based on motor, behavioral, cognitive, and functional assessments. Medical imaging, such as a CT scan or MRI scan, can show atrophy of the caudate nuclei early in the disease, as seen in the illustration to the right, but these changes are not, by themselves, diagnostic of<unk> . Cerebral atrophy can be seen in the advanced stages of the disease. Functional neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) and positron emission tomography (PET), can show changes in brain activity before the onset of physical symptoms, but they are experimental tools and are not used clinically. Predictive genetic testing Because<unk>  follows an autosomal dominant pattern of inheritance, a strong motivation exists for individuals who are at risk of inheriting it to seek a diagnosis. The genetic test for<unk>  consists of a blood test, which counts the numbers of CAG repeats in each of the HTT alleles. Cutoffs are given as follows: * At 40 or more CAG repeats, full penetrance allele (FPA) exists. A "positive test" or "positive result" generally refers to this case. A positive result is not considered a diagnosis, since it may be obtained decades before the symptoms begin. However, a negative test means that the individual does not carry the expanded copy of the gene and will not develop<unk> . The test will tell a person who originally had a 50% chance of inheriting the disease if their risk goes up to 100% or is eliminated. Persons who test positive for the disease will develop<unk>  sometime within their lifetimes, provided they live long enough for the disease to appear. * At 36 to 39 repeats, incomplete or reduced penetrance allele (RPA) may cause symptoms, usually later in the adult life. The maximum risk is 60% that a person with an RPA will be symptomatic at age 65, and 70% at 75. * At 27 to 35 repeats, intermediate allele (IA), or large normal allele, is not associated with symptomatic disease in the tested individual, but may expand upon further inheritance to give symptoms in offspring. * With 26 or fewer repeats, the result is not associated with<unk> . Testing before the onset of symptoms is a life-changing event and a very personal decision. The main reason given for choosing to test for<unk>  is to aid in career and family decisions. Predictive testing for<unk>  has been available via linkage analysis (which requires testing multiple family members) since 1986 and via direct mutation analysis since 1993. At that time, surveys indicated that 50–70% of at-risk individuals would have been interested in receiving testing, but since predictive testing has been offered far fewer choose to be tested. Over 95% of individuals at risk of inheriting<unk>  do not proceed with testing, mostly because it has no treatment. A key issue is the anxiety an individual experiences about not knowing whether they will eventually develop<unk> , compared to the impact of a positive result. Irrespective of the result, stress levels are lower two years after being tested, but the risk of suicide is increased after a positive test result. Individuals found to have not inherited the disorder may experience survivor guilt about family members who are affected. Other factors taken into account when considering testing include the possibility of discrimination and the implications of a positive result, which usually means a parent has an affected gene and that the individual's siblings will be at risk of inheriting it. In one study, genetic discrimination was found in 46% of individuals at risk for<unk> . It occurred at higher rates within personal relationships than health insurance or employment relations. Genetic counseling in<unk>  can provide information, advice and support for initial decision-making, and then, if chosen, throughout all stages of the testing process. Because of the implications of this test, patients who wish to undergo testing must complete three counseling sessions which provide information about<unk> 's. Counseling and guidelines on the use of genetic testing for<unk>  have become models for other genetic disorders, such as autosomal dominant cerebellar ataxia. Presymptomatic testing for<unk>  has also influenced testing for other illnesses with genetic variants such as polycystic kidney disease, familial Alzheimer's disease and breast cancer. The European Molecular Genetics Quality Network have published yearly external quality assessment scheme for molecular genetic testing for this disease and have developed best practice guidelines for genetic testing for<unk>  to assist in testing and reporting of results. Preimplantation genetic diagnosis Embryos produced using in vitro fertilization may be genetically tested for<unk>  using preimplantation genetic diagnosis. This technique, where one or two cells are extracted from a typically 4- to 8-cell embryo and then tested for the genetic abnormality, can then be used to ensure embryos affected with<unk>  genes are not implanted, so any offspring will not inherit the disease. Some forms of preimplantation genetic diagnosis—non-disclosure or exclusion testing—allow at-risk people to have<unk> -free offspring without revealing their own parental genotype, giving no information about whether they themselves are destined to develop<unk> . In exclusion testing, the embryo's DNA is compared with that of the parents and grandparents to avoid inheritance of the chromosomal region containing the<unk>  gene from the affected grandparent. In nondisclosure testing, only disease-free embryos are replaced in the uterus while the parental genotype and hence parental risk for<unk>  are never disclosed. Prenatal testing Obtaining a prenatal diagnosis for an embryo or fetus in the womb is also possible, using fetal genetic material acquired through chorionic villus sampling. An amniocentesis can be performed if the pregnancy is further along, within 14–18 weeks. This procedure looks at the amniotic fluid surrounding the baby for indicators of the<unk>  mutation. This, too, can be paired with exclusion testing to avoid disclosure of parental genotype. Prenatal testing can be done when parents have been diagnosed with<unk> , when they have had genetic testing showing the expansion of the HTTgene, or when they have a 50% chance of inheriting the disease. The parents can be counseled on their options, which include termination of pregnancy, and on the difficulties of a child with the identified gene. In addition, in at-risk pregnancies due to an affected male partner, noninvasive prenatal diagnosis can be performed by analyzing cell-free fetal DNA in a blood sample taken from the mother (via venipuncture) between six and 12 weeks of pregnancy. It has no procedure-related risk of miscarriage. Differential diagnosis About 99% of<unk>  diagnoses based on the typical symptoms and a family history of the disease are confirmed by genetic testing to have the expanded trinucleotide repeat that causes<unk> . Most of the remaining are called<unk> -like <unk> L) syndromes. The cause of most<unk> L diseases is unknown, but those with known causes are due to mutations in the prion protein gene <unk> L1), the junctophilin 3 gene <unk> L2), a recessively inherited unknown gene <unk> L3—only found in two families and poorly understood), and the gene encoding the TATA box-binding protein (SCA17, sometimes called<unk> L4). Other autosomal dominant diseases that can be misdiagnosed as<unk>  are dentatorubral-pallidoluysian atrophy and neuroferritinopathy. Also, some autosomal recessive disorders resemble sporadic cases of<unk> . These include chorea acanthocytosis and pantothenate kinase-associated neurodegeneration. One X-linked disorder of this type is McLeod syndrome.
Huntington's disease
Wilson's disease
Stratton Parker syndrome
Paraneoplastic syndrome
Sandhoff disease
Lupus
X-linked dystonia parkinsonism
Benign hereditary chorea