The length of the trinucleotide repeat accounts for 60% of the variation in the age symptoms appear and the rate they progress. A longer repeat results in an earlier age of onset and a faster progression of symptoms. Individuals with more than sixty repeats often develop the disease before age 20, while those with fewer than 40 repeats may not ever develop noticeable symptoms. The remaining variation is due to environmental factors and other genes that influence the mechanism of the disease.

Life expectancy in HD is generally around 20 years following the onset of visible symptoms. Most life-threatening complications result from muscle coordination and, to a lesser extent, behavioral changes induced by declining cognitive function. 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. Suicide is the third greatest cause of fatalities, with 7.3% of those with HD taking their own lives and up to 27% attempting to do so. It is unclear to what extent suicidal thoughts are influenced by behavioral symptoms, as they signify sufferers' desires to avoid the later stages of the disease. Other associated risks include choking, physical injury from falls, and malnutrition.

The late onset of Huntington's disease means it does not usually affect reproduction. The worldwide prevalence of HD is 5–10 cases per 100,000 persons, but varies greatly geographically as a result of ethnicity, local migration and past immigration patterns. Prevalence is similar for men and women. The rate of occurrence is highest in peoples of Western European descent, averaging around 7 per 100,000 people, and is lower in the rest of the world; e.g., one per million people of Asian and African descent. A 2013 epidemiological study of the prevalence of Huntington's disease in the UK between 1990 and 2010 found that the average prevalence for the UK was 12.3 per 100,000. Additionally, some localized areas have a much higher prevalence than their regional average. One of the highest incidences is in the isolated populations of the Lake Maracaibo region of Venezuela, where HD affects up to 700 per 100,000 persons. Other areas of high localization have been found in Tasmania and specific regions of Scotland, Wales and Sweden. Increased prevalence in some cases occurs due to a local founder effect, a historical migration of carriers into an area of geographic isolation. Some of these carriers have been traced back hundreds of years using genealogical studies. Genetic haplotypes can also give clues for the geographic variations of prevalence. Iceland, on the contrary, has a rather low prevalence of 1 per 100,000, despite the fact that Icelanders as a people are descended of the early Germanic tribes of Scandinavia which also gave rise to the Swedes; all cases with the exception of one going back nearly two centuries having derived from the offspring of a couple living early in the 19th century. Finland, as well, has a low incidence of only 2.2 per 100,000 people.

Until the discovery of a genetic test, statistics could only include clinical diagnosis based on physical symptoms and a family history of HD, excluding those who died of other causes before diagnosis. These cases can now be included in statistics; and, as the test becomes more widely available, estimates of the prevalence and incidence of the disorder are likely to increase.

The Huntington's disease-like syndromes (often abbreviated as HD-like or "HDL" syndromes) are a family of inherited neurodegenerative diseases that closely resemble Huntington's disease (HD) in that they typically produce a combination of chorea, cognitive decline or dementia and behavioural or psychiatric problems.

HDL1 is an unusual, autosomal dominant familial prion disease. Only described in one family, it is caused by an eight-octapeptide repeat insertion in the "PRNP" gene. More broadly, inherited prion diseases in general can mimic HD.

Many other neurological conditions are associated with acanthocytosis but are not considered 'core' acanthocytosis syndromes. The commonest are:

- Pantothenate kinase-associated neurodegeneration, an autosomal recessive condition caused by mutations in "PANK2".

- Huntington's disease-like syndrome type 2, an autosomal dominant condition caused by mutations in "JPH3" that closely resembles Huntington's disease.

- Bassen-Kornzweig disease, or Bassen-Kornzweig Syndrome (see also History).

- Levine-Critchley syndrome (see History).

- Paroxysmal movement disorders associated with GLUT1 mutations.

- Familial acanthocytosis with paroxysmal exertion-induced dyskinesias and epilepsy (FAPED).

- Some cases of mitochondrial disease.

McLeod syndrome is an X-linked recessive disorder caused by mutations in the "XK" gene encoding the Kx blood type antigen, one of the Kell antigens.

Like the other neuroacanthocytosis syndromes, McLeod syndrome causes movement disorder, cognitive impairment and psychiatric symptoms. The particular features of McLeod syndrome are heart problems such as arrhythmia and dilated cardiomyopathy (enlarged heart).

McLeod syndrome is very rare. There are approximately 150 cases of McLeod syndrome worldwide. Because of its X-linked mode of inheritance, it is much more prevalent in males.