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Regions of the brain have differing amounts and reliance on these types of neurons, and are affected accordingly. The remaining variation is attributed to environment and other genes that modify the mechanism of HD. In some cases the onset may be so late that symptoms are never noticed. Inheritance is independent of gender, and the phenotype does not skip generations.

This probability is sex-independent. Individuals with both genes affected are rare. For some time HD was thought to be the only disease for which possession of a second mutated gene did not affect symptoms and progression, [29] but it has since been found that it can affect the phenotype and the rate of progression. Early damage is most evident in the striatum , but as the disease progresses, other areas of the brain are also more conspicuously affected.

Early symptoms are attributable to functions of the striatum and its cortical connections—namely control over movement, mood and higher cognitive function. The highest concentrations are found in the brain and testes , with moderate amounts in the liver , heart , and lungs. It interacts with proteins which are involved in transcription, cell signaling , and intracellular transporting.

Caspase , an enzyme which plays a role in catalyzing apoptosis, is thought to be activated by the mutated gene through damaging the ubiquitin-protease system.

It also acts as an anti-apoptotic agent preventing programmed cell death and controls the production of brain-derived neurotrophic factor , a protein which protects neurons and regulates their creation during neurogenesis. HTT also facilitates vesicular transport and synaptic transmission and controls neuronal gene transcription. Over time, the aggregates accumulate to form inclusion bodies within cells, ultimately interfering with neuron function.

Inclusion bodies have been found in both the cell nucleus and cytoplasm. These include: effects on chaperone proteins , which help fold proteins and remove misfolded ones; interactions with caspases , which play a role in the process of removing cells ; the toxic effects of glutamine on nerve cells ; impairment of energy production within cells; and effects on the expression of genes.

Mutant huntingtin protein has been found to play a key role in mitochondrial dysfunction. Glutamine is not found in excessively high amounts in HD, but the interactions of the altered huntingtin protein with numerous proteins in neurons lead to an increased vulnerability to glutamine. It has been postulated that the increased vulnerability results in excitotoxic effects from normal glutamine levels.

The most prominent early effects are in a part of the basal ganglia called the neostriatum , which is composed of the caudate nucleus and putamen. Their functions are not fully understood, but current theories propose that they are part of the cognitive executive system [18] and the motor circuit.

To initiate a particular movement, the cerebral cortex sends a signal to the basal ganglia that causes the inhibition to be released. Damage to the basal ganglia can cause the release or reinstatement of the inhibitions to be erratic and uncontrolled, which results in an awkward start to motion or motions to be unintentionally initiated, or a motion to be halted before, or beyond, its intended completion. The accumulating damage to this area causes the characteristic erratic movements associated with HD.

Thus, the glutamines on CBP interact directly with the increased numbers of glutamine on the HTT chain and CBP gets pulled away from its typical location next to the nucleus. Even before the onset of symptoms, genetic testing can confirm if an individual or embryo carries an expanded copy of the trinucleotide repeat 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. If these are abrupt and have random timing and distribution, they suggest a diagnosis of HD. Cognitive or behavioral symptoms are rarely the first symptoms diagnosed; they are usually only recognized in hindsight or when they develop further.

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. 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 HD. A person who tests positive for the disease will develop HD sometime within their lifetime, provided he or she lives long enough for the disease to appear.

It may cause symptoms, usually later in the adult life. It is not associated with symptomatic disease in the tested individual, but may expand upon further inheritance to give symptoms in offspring.

It occurred at higher rates within personal relationships than health insurance or employment relations. 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 HD genes are not implanted, and therefore any offspring will not inherit the disease.

Some forms of preimplantation genetic diagnosis—non-disclosure or exclusion testing—allow at-risk people to have HD-free offspring without revealing their own parental genotype, giving no information about whether they themselves are destined to develop HD. In non-disclosure testing, only disease-free embryos are replaced in the uterus while the parental genotype and hence parental risk for HD are never disclosed. 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 HD mutation. The parents can be counseled on their options, which include termination of pregnancy , and on the difficulties of a child with the identified gene.

Other autosomal dominant diseases that can be misdiagnosed as HD are dentatorubral-pallidoluysian atrophy and neuroferritinopathy. There are also autosomal recessive disorders that resemble sporadic cases of HD.

These include chorea acanthocytosis and pantothenate kinase-associated neurodegeneration. One X-linked disorder of this type is McLeod syndrome. This is a feeding tube, permanently attached through the abdomen into the stomach , which reduces the risk of aspirating food and provides better nutritional management. Physical therapists may implement fall risk assessment and prevention, as well as strengthening, stretching, and cardiovascular exercises.

Walking aids may be prescribed as appropriate. Physical therapists also prescribe breathing exercises and airway clearance techniques with the development of respiratory problems. Participation in rehabilitation programs during early to middle stage of the disease may be beneficial as it translates into long term maintenance of motor and functional performance.

Rehabilitation during the late stage aims to compensate for motor and functional losses. Genetic counseling benefits these individuals by updating their knowledge, seeking to dispel any unfounded beliefs that they may have, and helping them consider their future options and plans. Also covered is information concerning family planning choices, care management, and other considerations. A longer repeat results in an earlier age of onset and a faster progression of symptoms.

The largest risk is pneumonia , which causes death in one third of those with HD. As the ability to synchronize movements deteriorates, difficulty clearing the lungs and an increased risk of aspirating food or drink both increase the risk of contracting pneumonia. The second greatest risk is heart disease , which causes almost a quarter of fatalities of those with HD.


Huntington's disease



Huntington's disease



Chorée de Huntington



Maladie de Huntington


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