Color blindness

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Color blindness
Synonyms	Colour blindness, color deficiency, impaired color vision
Example of an Ishihara color test plate. With properly configured computer displays, people with normal vision should see the number "74". Many people who are color blind see it as "21", and those with total color blindness may not see any numbers.
Specialty	Ophthalmology
Symptoms	Decreased ability to see colors
Duration	Long term
Causes	Genetic (inherited usually X-linked)
Diagnostic method	Ishihara color test
Treatment	Adjustments to teaching methods, mobile apps
Frequency	Red-green: 8% males, 0.5% females (Northern European descent)

Color blindness, also known as color vision deficiency, is the decreased ability to see color or differences in color. Simple tasks such as selecting ripe fruit, choosing clothing, and reading traffic lights can be more challenging. Color blindness may also make some educational activities more difficult. However, problems are generally minor, and most people find that they can adapt. People with total color blindness (achromatopsia) may also have decreased visual acuity and be uncomfortable in bright environments.

The most common cause of color blindness is an inherited problem in the development of one or more of the three sets of color sensing cones in the eye. Males are more likely to be color blind than females, as the genes responsible for the most common forms of color blindness are on the X chromosome. As females have two X chromosomes, a defect in one is typically compensated for by the other, while males only have one X chromosome. Color blindness can also result from physical or chemical damage to the eye, optic nerve or parts of the brain. Diagnosis is typically with the Ishihara color test; however, a number of other testing methods also exist.

There is no cure for color blindness. Diagnosis may allow a person's teacher to change their method of teaching to accommodate the decreased ability to recognize colors. Special lenses may help people with red-green color blindness when under bright conditions. There are also mobile apps that can help people identify colors.

Red-green color blindness is the most common form, followed by blue-yellow color blindness and total color blindness. Red-green color blindness affects up to 8% of males and 0.5% of females of Northern European descent. The ability to see color also decreases in old age. Being color blind may make people ineligible for certain jobs in certain countries. This may include being a pilot, train driver and working in the armed forces. The effect of color blindness on artistic ability, however, is controversial. The ability to draw appears to be unchanged, and a number of famous artists are believed to have been color blind.

Signs and symptoms

Simulation of the normal (above) and dichromatic (below) perception of red and green apples

 

Horizontal traffic light in Halifax, Nova Scotia, Canada

In almost all cases, color blind people retain blue-yellow discrimination, and most color-blind individuals are anomalous trichromats rather than complete dichromats. In practice, this means that they often retain a limited discrimination along the red-green axis of color space, although their ability to separate colors in this dimension is reduced. Color blindness very rarely refers to complete monochromatism.

Dichromats often confuse red and green items. For example, they may find it difficult to distinguish a Braeburn apple from a Granny Smith or red from green of traffic lights without other clues—for example, shape or position. Dichromats tend to learn to use texture and shape clues and so may be able to penetrate camouflage that has been designed to deceive individuals with normal color vision.

Colors of traffic lights are confusing to some dichromats as there is insufficient apparent difference between the red/amber traffic lights and sodium street lamps; also, the green can be confused with a grubby white lamp. This is a risk on high-speed undulating roads where angular cues cannot be used. British Rail color lamp signals use more easily identifiable colors: The red is blood red, the amber is yellow and the green is a bluish color. Most British road traffic lights are mounted vertically on a black rectangle with a white border (forming a "sighting board") and so dichromats can more easily look for the position of the light within the rectangle—top, middle or bottom. In the eastern provinces of Canada horizontally mounted traffic lights are generally differentiated by shape to facilitate identification for those with color blindness. In the United States, this is not done by shape but by position, as the red light is always on the left if the light is horizontal, or on top if the light is vertical. However, a lone flashing light (e.g. red for stop, yellow for caution) is still problematic.

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  Normal sight
  
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  Deuteranopia sight
  
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  Tritanopia sight
  
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  Monochromacy sight
  

Types

These color charts show how different colorblind people see compared to a person with normal color vision.

Types of color blindness and the terms used
 

	Cone system	Red		Green		Blue
	N=normal A=anomalous	N	A	N	A	N	A
1	Normal vision	.	.	.	.	.	.	Trichromat	Normal
2	Protanomaly	.	.	.	.	.	.	Anomalous Trichromat	Partially color blind	Red-green
3	Protanopia	.	.	.	.	.	.	Dichromat	Partially color blind	Red-green
4	Deuteranomaly	.	.	.	.	.	.	Anomalous Trichromat	Partially color blind	Red-green
5	Deuteranopia	.	.	.	.	.	.	Dichromat	Partially color blind	Red-green
6	Tritanomaly	.	.	.	.	.	.	Anomalous Trichromat	Partially color blind	Blue-yellow
7	Tritanopia	.	.	.	.	.	.	Dichromat	Partially color blind	Blue-yellow
8	Achromatopsia	.	.	.	.	.	.	Monochromat	Totally color blind
9	Tetrachromat	.	.	.	.	.	.
10		.	.	.	.	.	.

Based on clinical appearance, color blindness may be described as total or partial. Total color blindness is much less common than partial color blindness. There are two major types of color blindness: difficulty distinguishing between red and green, and difficulty distinguishing between blue and yellow.

Immunofluorescent imaging is a way to determine red-green color coding. Conventional color coding is difficult for individuals with red–green color blindness (protanopia or deuteranopia) to discriminate. Replacing red with magenta or green with turquoise improves visibility for such individuals.

The different kinds of inherited color blindness result from partial or complete loss of function of one or more of the three different cone systems. When one cone system is compromised, dichromacy results. The most frequent forms of human color blindness result from problems with either the middle (green) or long (red) wavelength sensitive cone systems, and make it hard to discriminate reds, yellows, and greens from one another. They are collectively referred to as "red-green color blindness", though the term is an over-simplification and is somewhat misleading. Other forms of color blindness are much more rare. They include problems in discriminating blues from greens and yellows from reds/pinks, and the rarest form of all, complete color blindness or monochromacy, where one cannot distinguish any color from grey, as in a black-and-white movie or photograph.
Protanopes, deuteranopes, and tritanopes are dichromats; that is, they can match any color they see with some mixture of just two primary colors (in contrast to those with normal sight (trichromats) who can distinguish three primary colors). Dichromats usually know they have a color vision problem, and it can affect their daily lives. Out of the male population, 2% have severe difficulties distinguishing between red, orange, yellow, and green. (Orange and yellow are different combinations of red and green light.) Colors in this range, which appear very different to a normal viewer, appear to a dichromat to be the same or a similar color. The terms protanopia, deuteranopia, and tritanopia come from Greek, and respectively mean "inability to see (anopia) with the first (prot-), second (deuter-), or third (trit-) [cone]".

Anomalous trichromacy is the least serious type of color deficiency. People with protanomaly, deuteranomaly, or tritanomaly are trichromats, but the color matches they make differ from the normal. They are called anomalous trichromats. In order to match a given spectral yellow light, protanomalous observers need more red light in a red/green mixture than a normal observer, and deuteranomalous observers need more green. From a practical standpoint though, many protanomalous and deuteranomalous people have very little difficulty carrying out tasks that require normal color vision. Some may not even be aware that their color perception is in any way different from normal.

Protanomaly and deuteranomaly can be diagnosed using an instrument called an anomaloscope, which mixes spectral red and green lights in variable proportions, for comparison with a fixed spectral yellow. If this is done in front of a large audience of males, as the proportion of red is increased from a low value, first a small proportion of the audience will declare a match, while most will see the mixed light as greenish; these are the deuteranomalous observers. Next, as more red is added the majority will say that a match has been achieved. Finally, as yet more red is added, the remaining, protanomalous, observers will declare a match at a point where normal observers will see the mixed light as definitely reddish.

Red-green color blindness

Protanopia, deuteranopia, protanomaly, and deuteranomaly are commonly inherited forms of red-green color blindness which affect a substantial portion of the human population. Those affected have difficulty with discriminating red and green hues due to the absence or mutation of the red or green retinal photoreceptors. It is sex-linked: genetic red-green color blindness affects males much more often than females, because the genes for the red and green color receptors are located on the X chromosome, of which males have only one and females have two. Females (XX) are red-green color blind only if both their X chromosomes are defective with a similar deficiency, whereas males (XY) are color blind if their single X chromosome is defective.

The gene for red-green color blindness is transmitted from a color blind male to all his daughters, who are usually heterozygote carriers and are thus unaffected. In turn, a carrier woman has a 50% chance of passing on a mutated X chromosome region to each of her male offspring. The sons of an affected male will not inherit the trait from him, since they receive his Y chromosome and not his (defective) X chromosome. Should an affected male have children with a carrier or colorblind woman, their daughters may be colorblind by inheriting an affected X chromosome from each parent.

Because one X chromosome is inactivated at random in each cell during a woman's development, deuteranomalous heterozygotes (i.e. female carriers of deuteranomaly) may be tetrachromats, because they will have the normal long wave (red) receptors, the normal medium wave (green) receptors, the abnormal medium wave (deuteranomalous) receptors and the normal autosomal short wave (blue) receptors in their retinas. The same applies to the carriers of protanomaly (who have two types of long wave receptors, normal medium wave receptors, and normal autosomal short wave receptors in their retinas). If, by rare chance, a woman is heterozygous for both protanomaly and deuteranomaly, she could be pentachromatic. This situation could arise if, for instance, she inherited the X chromosome with the abnormal long wave gene (but normal medium wave gene) from her mother who is a carrier of protanomaly, and her other X chromosome from a deuteranomalous father. Such a woman would have a normal and an abnormal long wave receptor, a normal and abnormal medium wave receptor, and a normal autosomal short wave receptor—5 different types of color receptors in all. The degree to which women who are carriers of either protanomaly or deuteranomaly are demonstrably tetrachromatic and require a mixture of four spectral lights to match an arbitrary light is very variable. In many cases it is almost unnoticeable, but in a minority the tetrachromacy is very pronounced. However, Jameson et al. have shown that with appropriate and sufficiently sensitive equipment it can be demonstrated that any female carrier of red-green color blindness (i.e. heterozygous protanomaly, or heterozygous deuteranomaly) is a tetrachromat to a greater or lesser extent.

Since deuteranomaly is by far the most common form of red-green blindness among men of northwestern European descent (with an incidence of 8%) it follows that the proporrtion of carriers (and of potential deuteranomalous tetrachromats) among the females of that genetic stock is 14.7% (i.e. 92% × 8% × 2), based on the Hardy–Weinberg principle.

Illustration of the distribution of cone cells in the fovea of an individual with normal color vision (left), and a color blind (protanopic) retina. The center of the fovea holds very few blue-sensitive cones.

• Protanopia (1% of males): Lacking the red cones for long-wavelength sensitive retinal cones, those with this condition are unable to distinguish between colors in the green-yellow-red section of the spectrum. They have a neutral point at a cyan-like wavelength around 492 nm (see spectral color for comparison)—that is, they cannot discriminate light of this wavelength from white. For a protanope, the brightness of red, orange, and yellow are much reduced compared to normal. This dimming can be so pronounced that reds may be confused with black or dark gray, and red traffic lights may appear to be extinguished. They may learn to distinguish reds from yellows primarily on the basis of their apparent brightness or lightness, not on any perceptible hue difference. Violet, lavender, and purple are indistinguishable from various shades of blue because their reddish components are so dimmed as to be invisible. For example, pink flowers, reflecting both red light and blue light, may appear just blue to the protanope. A very few people have been found who have one normal eye and one protanopic eye. These unilateral dichromats report that with only their protanopic eye open, they see wavelengths shorter than neutral point as blue and those longer than it as yellow. This is a rare form of color blindness.

• Deuteranopia (1% of males): Lacking the green cones for medium-wavelength cones, those affected are again unable to distinguish between colors in the green-yellow-red section of the spectrum. Their neutral point is at a slightly longer wavelength, 498 nm, a more greenish hue of cyan. A deuteranope suffers the same hue discrimination problems as protanopes, but without the abnormal dimming. Purple colors are not perceived as something opposite to spectral colors; all these appear similarly. This form of colorblindness is also known as Daltonism after John Dalton (his diagnosis was confirmed as deuteranopia in 1995, some 150 years after his death, by DNA analysis of his preserved eyeball). Equivalent terms for Daltonism in Romanic languages such as daltonismo (Spanish, Portuguese and Italian), daltonisme (French), daltonism (Romanian) are still used to describe color blindess in a broad sense or deuteranopia in a more restricted sense. Deuteranopic unilateral dichromats report that with only their deuteranopic eye open, they see wavelengths shorter than neutral point as blue and longer than it as yellow.

• Protanomaly (1% of males, 0.01% of females): Having a mutated form of the long-wavelength (red) pigment, whose peak sensitivity is at a shorter wavelength than in the normal retina, protanomalous individuals are less sensitive to red light than normal. This means that they are less able to discriminate colors, and they do not see mixed lights as having the same colors as normal observers. They also suffer from a darkening of the red end of the spectrum. This causes reds to reduce in intensity to the point where they can be mistaken for black. Protanomaly is a fairly rare form of color blindness, making up about 1% of the male population. Both protanomaly and deuteranomaly are carried on the X chromosome.

• Deuteranomaly (most common—6% of males, 0.4% of females): These individuals have a mutated form of the medium-wavelength (green) pigment. The medium-wavelength pigment is shifted towards the red end of the spectrum resulting in a reduction in sensitivity to the green area of the spectrum. Unlike in protanomaly, the intensity of colors is unchanged. The deuteranomalous person is considered "green weak". For example, in the evening, dark green cars appear to be black to deuteranomalous people. As with protanomates, deuteranomates are poor at discriminating small differences in hues in the red, orange, yellow, green region of the spectrum. They make errors in the naming of hues in this region because the hues appear somewhat shifted towards green. However, unlike protanomates, deuteranomalous people do not have the loss of "brightness" problem.

Blue-yellow color blindness

Those with tritanopia and tritanomaly have difficulty discriminating between bluish and greenish hues, as well as yellowish and reddish hues.

Color blindness involving the inactivation of the short-wavelength sensitive cone system (whose absorption spectrum peaks in the bluish-violet) is called tritanopia or, loosely, blue-yellow color blindness. The tritanope's neutral point occurs near a yellowish 570 nm; green is perceived at shorter wavelengths and red at longer wavelengths. Mutation of the short-wavelength sensitive cones is called tritanomaly. Tritanopia is equally distributed among males and females. Jeremy H. Nathans (with the Howard Hughes Medical Institute) demonstrated that the gene coding for the blue receptor lies on chromosome 7, which is shared equally by males and females. Therefore, it is not sex-linked. This gene does not have any neighbor whose DNA sequence is similar. Blue color blindness is caused by a simple mutation in this gene.

• Tritanopia (less than 1% of males and females): Lacking the short-wavelength cones, those affected see short-wavelength colors (blue, indigo and a spectral violet) greenish and drastically dimmed, some of these colors even as black. Yellow is indistinguishable from pink, and purple colors are perceived as various shades of red. This form of color blindness is not sex-linked.

• Tritanomaly (equally rare for males and females [0.01% for both]): Having a mutated form of the short-wavelength (blue) pigment. The short-wavelength pigment is shifted towards the green area of the spectrum. This is the rarest form of anomalous trichromacy color blindness. Unlike the other anomalous trichromacy color deficiencies, the mutation for this color blindness is carried on chromosome 7. Therefore, it is equally prevalent in both male and female populations. The OMIM gene code for this mutation is 304000 "Colorblindness, Partial Tritanomaly".

Total color blindness

Total color blindness is defined as the inability to see color. Although the term may refer to acquired disorders such as cerebral achromatopsia also known as color agnosia, it typically refers to congenital color vision disorders (i.e. more frequently rod monochromacy and less frequently cone monochromacy).

In cerebral achromatopsia, a person cannot perceive colors even though the eyes are capable of distinguishing them. Some sources do not consider these to be true color blindness, because the failure is of perception, not of vision. They are forms of visual agnosia.

Monochromacy is the condition of possessing only a single channel for conveying information about color. Monochromats possess a complete inability to distinguish any colors and perceive only variations in brightness. It occurs in two primary forms:

1. Rod monochromacy, frequently called achromatopsia, where the retina contains no cone cells, so that in addition to the absence of color discrimination, vision in lights of normal intensity is difficult. While normally rare, achromatopsia is very common on the island of Pingelap, a part of the Pohnpei state, Federated States of Micronesia, where it is called maskun: about 10% of the population there has it, and 30% are unaffected carriers. The island was devastated by a storm in the 18th century (an example of a genetic bottleneck) and one of the few male survivors carried a gene for achromatopsia. The population grew to several thousand before foreign troops introduced diseases to the island in the 1940s.
2. Cone monochromacy is the condition of having both rods and cones, but only a single kind of cone. A cone monochromat can have good pattern vision at normal daylight levels, but will not be able to distinguish hues. Blue cone monochromacy (X chromosome) is caused by lack of functionality of L and M cones (red and green). It is encoded at the same place as red-green color blindness on the X chromosome. Peak spectral sensitivities are in the blue region of the visible spectrum (near 440 nm). People with this condition generally show nystagmus ("jiggling eyes"), photophobia (light sensitivity), reduced visual acuity, and myopia (nearsightedness). Visual acuity usually falls to the 20/50 to 20/400 range.

Causes

Color vision deficiencies can be classified as acquired or inherited.

• Acquired: Diseases, drugs (e.g., Plaquenil), and chemicals may cause color blindness.
• Inherited: There are three types of inherited or congenital color vision deficiencies: monochromacy, dichromacy, and anomalous trichromacy.

• • Monochromacy, also known as "total color blindness", is the lack of ability to distinguish colors (and thus the person views everything as if it were on a black and white television); caused by cone defect or absence. Monochromacy occurs when two or all three of the cone pigments are missing and color and lightness vision is reduced to one dimension.
    • Rod monochromacy (achromatopsia) is an exceedingly rare, nonprogressive inability to distinguish any colors as a result of absent or nonfunctioning retinal cones. It is associated with light sensitivity (photophobia), involuntary eye oscillations (nystagmus), and poor vision.
    • Cone monochromacy is a rare total color blindness that is accompanied by relatively normal vision, electroretinogram, and electrooculogram. Cone monochromacy can also be a result of having more than one type of dichromatic color blindness. People who have, for instance, both protanopia and tritanopia are considered to have cone monochromacy. Since cone monochromacy is the lack of/damage of more than one cone in retinal environment, having two types of dichromacy would be an equivalent.
  • Dichromacy is hereditary. Protanopia and deuteranopia are hereditary and sex-linked, affecting predominantly males.
    • Protanopia is caused by the complete absence of red retinal photoreceptors. Protans have difficulties distinguishing between blue and green colors and also between red and green colors. It is a form of dichromatism in which the subject can only perceive light wavelengths from 400 nm to 650 nm, instead of the usual 700 nm. Pure reds cannot be seen, instead appearing black; purple colors cannot be distinguished from blues; more orange-tinted reds may appear as dim yellows, and all orange-yellow-green shades of too long a wavelength to stimulate the blue receptors appear as a similar yellow hue. It is present in 1% of males.
    • Deuteranopia affects hue discrimination in a similar way to protanopia, but without the dimming effect. Again, it is found in about 1% of the male population.
    • Tritanopia is a very rare color vision disturbance in which only the red and the green cone pigments are present, with a total absence of blue retinal receptors. Blues appear greenish, yellows and oranges appear pinkish, and purple colors appear deep red. It is related to chromosome 7; thus unlike protanopia and deuteranopia, tritanopia and tritanomaly are not sex-linked traits and can be acquired rather than inherited and can be reversed in some cases.
  • Anomalous trichromacy is a common type of inherited color vision deficiency, occurring when one of the three cone pigments is altered in its spectral sensitivity.
    • Protanomaly is a mild color vision defect in which an altered spectral sensitivity of red retinal receptors (closer to green receptor response) results in poor red-green hue discrimination. It is hereditary, sex-linked, and present in 1% of males. In contrast to other defects, in this case the L-cone is present but malfunctioning, whereas in protanopia the L-cone is completely missing.
    • Deuteranomaly, caused by a similar shift in the green retinal receptors, is by far the most common type of color vision deficiency, mildly affecting red-green hue discrimination in 5% of European males. It is hereditary and sex-linked. In contrast to deuteranopia, the green-sensitive cones are not missing but malfunctioning.
    • Tritanomaly is a rare, hereditary color vision deficiency affecting blue-green and yellow-red/pink hue discrimination. It is related to chromosome 7. In contrast to tritanopia, the S-cone is malfunctioning but not missing.

Genetics

X-linked recessive inheritance

Color blindness is typically an inherited genetic disorder. It is most commonly inherited from mutations on the X chromosome, but the mapping of the human genome has shown there are many causative mutations—mutations capable of causing color blindness originate from at least 19 different chromosomes and 56 different genes (as shown online at the Online Mendelian Inheritance in Man (OMIM)).

Two of the most common inherited forms of color blindness are protanomaly (and, more rarely, protanopia–the two together often known as "protans") and deuteranomaly (or, more rarely, deuteranopia—the two together often referred to as "deutans"). Both "protans" and "deutans" (of which the deutans are by far the most common) are known as "red-green color-blind". They comprise about 8% of human males and 0.6% of females of Northern European ancestry.

Some of the inherited diseases known to cause color blindness are:

• cone dystrophy
• cone-rod dystrophy
• achromatopsia (also called rod monochromatism, stationary cone dystrophy or cone dysfunction syndrome)
• blue cone monochromatism (also called blue cone monochromacy or X-linked achromatopsia)
• Leber's congenital amaurosis
• retinitis pigmentosa (initially affects rods but can later progress to cones and therefore color blindness).

Inherited color blindness can be congenital (from birth), or it can commence in childhood or adulthood. Depending on the mutation, it can be stationary, that is, remain the same throughout a person's lifetime, or progressive. As progressive phenotypes involve deterioration of the retina and other parts of the eye, certain forms of color blindness can progress to legal blindness, i.e. an acuity of 6/60 (20/200) or worse, and often leave a person with complete blindness.

Color blindness always pertains to the cone photoreceptors in retinas, as it is the cones that detect the color frequencies of light.

About 8% of males, and 0.6% of females, are red-green color blind in some way or another, whether it is one color, a color combination, or another mutation. Males are at a greater risk of inheriting an X-linked mutation because males only have one X chromosome (XY, with the Y chromosome carrying altogether different genes from the X chromosome), and females have two (XX); if a woman inherits a normal X chromosome in addition to the one that carries the mutation, she will not display the mutation. Men do not have a second X chromosome to override the chromosome that carries the mutation. If 8% of variants of a given gene are defective, the probability of a single copy being defective is 8%, but the probability that two copies are both defective is 0.08², i.e. 0.64%.

Other causes

Other causes of color blindness include brain or retinal damage caused by shaken baby syndrome, accidents and other traumas which produce swelling of the brain in the occipital lobe, and damage to the retina caused by exposure to ultraviolet light (wavelengths 10 to 300 nm). Damage often presents itself later in life.

Color blindness may also present itself in the range of degenerative diseases of the eye, such as age-related macular degeneration, and as part of the retinal damage caused by diabetes. Vitamin A deficiency may also cause color blindness.

Some subtle forms of color blindness may be associated with chronic solvent-induced encephalopathy (CSE), caused by long-time exposure to solvent vapors.

Red–green color blindness can be caused by ethambutol, a drug used in the treatment of tuberculosis.

Mechanism

The typical human retina contains two kinds of light cells: the rod cells (active in low light) and the cone cells (active in normal daylight). Normally, there are three kinds of cone cells, each containing a different pigment, which are activated when the pigments absorb light. The spectral sensitivities of the cones differ; one is most sensitive to short wavelengths, one to medium wavelengths, and the third to medium-to-long wavelengths within the visible spectrum, with their peak sensitivities in the blue, green, and yellow-green regions of the spectrum, respectively. The absorption spectra of the three systems overlap, and combine to cover the visible spectrum. These receptors are known as short (S), medium (M), and long (L) wavelength cones, but are also often referred to as blue, green, and red cones, although this terminology is inaccurate.

The receptors are each responsive to a wide range of wavelengths. For example, the long wavelength "red" receptor has its peak sensitivity in the yellow-green, some way from the red end (longest wavelength) of the visible spectrum. The sensitivity of normal color vision actually depends on the overlap between the absorption ranges of the three systems: different colors are recognized when the different types of cone are stimulated to different degrees. Red light, for example, stimulates the long wavelength cones much more than either of the others, and reducing the wavelength causes the other two cone systems to be increasingly stimulated, causing a gradual change in hue.

Many of the genes involved in color vision are on the X chromosome, making color blindness much more common in males than in females because males only have one X chromosome, while females have two. Because this is an X-linked trait, an estimated 2–3% of women have a 4th color cone and can be considered tetrachromats. One such woman has been reported to be a true or functional tetrachromat, as she can discriminate colors most other people can't.

Diagnosis

An Ishihara test image as seen by subjects with normal color vision and by those with a variety of color deficiencies

The Ishihara color test, which consists of a series of pictures of colored spots, is the test most often used to diagnose red-green color deficiencies. A figure (usually one or more Arabic digits) is embedded in the picture as a number of spots in a slightly different color, and can be seen with normal color vision, but not with a particular color defect. The full set of tests has a variety of figure/background color combinations, and enable diagnosis of which particular visual defect is present. The anomaloscope, described above, is also used in diagnosing anomalous trichromacy.

Position yourself about 75cm from your monitor so that the colour test image you are looking at is at eye level, read the description of the image and see what you can see!! It is not necessary in all cases to use the entire set of images. In a large scale examination the test can be simplified to six tests; test, one of tests 2 or 3, one of tests 4, 5, 6, or 7, one of tests 8 or 9, one of tests 10, 11, 12, or 13 and one of tests 14 or 15.

Because the Ishihara color test contains only numerals, it may not be useful in diagnosing young children, who have not yet learned to use numbers. In the interest of identifying these problems early on in life, alternative color vision tests were developed using only symbols (square, circle, car).

Besides the Ishihara color test, the US Navy and US Army also allow testing with the Farnsworth Lantern Test. This test allows 30% of color deficient individuals, whose deficiency is not too severe, to pass.

Another test used by clinicians to measure chromatic discrimination is the Farnsworth-Munsell 100 hue test. The patient is asked to arrange a set of colored caps or chips to form a gradual transition of color between two anchor caps.

The HRR color test (developed by Hardy, Rand, and Rittler) is a red-green color test that, unlike the Ishihara, also has plates for the detection of the tritan defects.

Most clinical tests are designed to be fast, simple, and effective at identifying broad categories of color blindness. In academic studies of color blindness, on the other hand, there is more interest in developing flexible tests to collect thorough datasets, identify copunctal points, and measure just noticeable differences.

Management

There is generally no treatment to cure color deficiencies. ″The American Optometric Association reports a contact lens on one eye can increase the ability to differentiate between colors, though nothing can make you truly see the deficient color.″

Lenses

Optometrists can supply colored spectacle lenses or a single red-tint contact lens to wear on the non-dominant eye, but although this may improve discrimination of some colors, it can make other colors more difficult to distinguish. A 1981 review of various studies to evaluate the effect of the X-chrom contact lens concluded that, while the lens may allow the wearer to achieve a better score on certain color vision tests, it did not correct color vision in the natural environment. A case history using the X-Chrom lens for a rod monochromat is reported and an X-Chrom manual is online.

Lenses that filter certain wavelengths of light can allow people with a cone anomaly, but not dichromacy, to see better separation of colors, especially those with classic "red/green" color blindness. They work by notching out wavelengths that strongly stimulate both red and green cones in a deuter- or protanomalous person, improving the distinction between the two cones' signals. As of 2013, sunglasses that notch out color wavelengths are available commercially.

Apps

Many mobile applications have been developed to help colorblind people to view colors in a better way. Many applications launch a simulation of colorblindness to allow people with normal vision to understand how people with color blindness see the world.

The GNOME desktop environment provides colorblind accessibility using the gnome-mag and the libcolorblind software. Using a gnome applet, the user may switch a color filter on and off, choosing from a set of possible color transformations that will displace the colors in order to disambiguate them. The software enables, for instance, a colorblind person to see the numbers in the Ishihara test.

Epidemiology

Rates of color blindness

	Males	Females
Dichromacy	2.4%	0.03%
Protanopia (red deficient: L cone absent)	1.3%	0.02%
Deuteranopia (green deficient: M cone absent)	1.2%	0.01%
Tritanopia (blue deficient: S cone absent)	0.001%	0.03%
Anomalous trichromacy	6.3%	0.37%
Protanomaly (red deficient: L cone defect)	1.3%	0.02%
Deuteranomaly (green deficient: M cone defect)	5.0%	0.35%
Tritanomaly (blue deficient: S cone defect)	0.0001%	0.0001%

Color blindness affects a large number of individuals, with protanopia and deuteranopia being the most common types. In individuals with Northern European ancestry, as many as 8 percent of men and 0.4 percent of women experience congenital color deficiency.

The number affected varies among groups. Isolated communities with a restricted gene pool sometimes produce high proportions of color blindness, including the less usual types. Examples include rural Finland, Hungary, and some of the Scottish islands. In the United States, about 7 percent of the male population—or about 10.5 million men—and 0.4 percent of the female population either cannot distinguish red from green, or see red and green differently from how others do (Howard Hughes Medical Institute, 2006). More than 95 percent of all variations in human color vision involve the red and green receptors in male eyes. It is very rare for males or females to be "blind" to the blue end of the spectrum.

Prevalence of red–green color blindness among males

Population	Number studied	%
Arabs (Druzes)	337	10.0
Aboriginal Australians	4,455	1.9
Belgians	9,540	7.4
Bosnians	4,836	6.2
Britons	16,180	6.6
Chinese	1,164	6.9
DR Congolese	929	1.7
Dutch	3,168	8.0
Eskimo	297	2.5
Fijians	608	0.8
French	1,243	8.6
Germans	7,861	7.7
Hutu	1,000	2.9
Indians (Andhra Pradesh)	292	7.5
Iranians	16,180	6.6
Japanese	259,000	4.0
Mexicans	571	2.3
Navajo	571	2.3
Norwegians	9,047	9.0
Russians	1,343	9.2
Scots	463	7.8
Swiss	2,000	8.0
Tibetans	241	5.0
Tswana	407	2.0
Tutsi	1,000	2.5
Serbs	4,750	7.4

History

An 1895 illustration of normal vision and various kinds of color blindness

The first scientific paper on the subject of color blindness, Extraordinary facts relating to the vision of colours, was published by the English chemist John Dalton in 1798 after the realization of his own color blindness. Because of Dalton's work, the general condition has been called daltonism, although in English this term is now used only for deuteranopia.

Society and culture

Design implications

Testing the colors of a web chart, (center), to ensure that no information is lost to the various forms of color blindness.

Color codes present particular problems for those with color deficiencies as they are often difficult or impossible for them to perceive.

Good graphic design avoids using color coding or using color contrasts alone to express information; this not only helps color blind people, but also aids understanding by normally sighted people by providing them with multiple reinforcing cues.

Designers need to take into account that color-blindness is highly sensitive to differences in material. For example, a red-green colorblind person who is incapable of distinguishing colors on a map printed on paper may have no such difficulty when viewing the map on a computer screen or television. In addition, some color blind people find it easier to distinguish problem colors on artificial materials, such as plastic or in acrylic paints, than on natural materials, such as paper or wood. Third, for some color blind people, color can only be distinguished if there is a sufficient "mass" of color: thin lines might appear black, while a thicker line of the same color can be perceived as having color.

Designers should also note that red-blue and yellow-blue color combinations are generally safe. So instead of the ever-popular "red means bad and green means good" system, using these combinations can lead to a much higher ability to use color coding effectively. This will still cause problems for those with monochromatic color blindness, but it is still something worth considering.

When the need to process visual information as rapidly as possible arises, for example in an emergency situation, the visual system may operate only in shades of gray, with the extra information load in adding color being dropped. This is an important possibility to consider when designing, for example, emergency brake handles or emergency phones.

Occupations

Color blindness may make it difficult or impossible for a person to engage in certain occupations. Persons with color blindness may be legally or practically barred from occupations in which color perception is an essential part of the job (e.g., mixing paint colors), or in which color perception is important for safety (e.g., operating vehicles in response to color-coded signals). This occupational safety principle originates from the Lagerlunda train crash of 1875 in Sweden. Following the crash, Professor Alarik Frithiof Holmgren, a physiologist, investigated and concluded that the color blindness of the engineer (who had died) had caused the crash. Professor Holmgren then created the first test using different-colored skeins to exclude people from jobs in the transportation industry on the basis of color blindness. However, there is a claim that there is no firm evidence that color deficiency did cause the collision, or that it might have not been the sole cause.

Color vision is important for occupations using telephone or computer networking cabling, as the individual wires inside the cables are color-coded using green, orange, brown, blue and white colors. Electronic wiring, transformers, resistors, and capacitors are color-coded as well, using black, brown, red, orange, yellow, green, blue, violet, gray, white, silver, gold.

Driving

Some countries have refused to grant driving licenses to individuals with color blindness. In Romania, there is an ongoing campaign to remove the legal restrictions that prohibit colorblind citizens from getting drivers' licenses.

The usual justification for such restrictions is that drivers of motor vehicles must be able to recognize color-coded signals, such as traffic lights or warning lights.

Piloting aircraft

While many aspects of aviation depend on color coding, only a few of them are critical enough to be interfered with by some milder types of color blindness. Some examples include color-gun signaling of aircraft that have lost radio communication, color-coded glide-path indications on runways, and the like. Some jurisdictions restrict the issuance of pilot credentials to persons who suffer from color blindness for this reason. Restrictions may be partial, allowing color-blind persons to obtain certification but with restrictions, or total, in which case color-blind persons are not permitted to obtain piloting credentials at all.

In the United States, the Federal Aviation Administration requires that pilots be tested for normal color vision as part of their medical clearance in order to obtain the required medical certificate, a prerequisite to obtaining a pilot's certification. If testing reveals color blindness, the applicant may be issued a license with restrictions, such as no night flying and no flying by color signals—such a restriction effectively prevents a pilot from holding certain flying occupations, such as that of an airline pilot, although commercial pilot certification is still possible, and there are a few flying occupations that do not require night flight and thus are still available to those with restrictions due to color blindness (e.g., agricultural aviation). The government allows several types of tests, including medical standard tests (e.g., the Ishihara, Dvorine, and others) and specialized tests oriented specifically to the needs of aviation. If an applicant fails the standard tests, they will receive a restriction on their medical certificate that states: "Not valid for night flying or by color signal control". They may apply to the FAA to take a specialized test, administered by the FAA. Typically, this test is the "color vision light gun test". For this test an FAA inspector will meet the pilot at an airport with an operating control tower. The color signal light gun will be shone at the pilot from the tower, and they must identify the color. If they pass they may be issued a waiver, which states that the color vision test is no longer required during medical examinations. They will then receive a new medical certificate with the restriction removed. This was once a Statement of Demonstrated Ability (SODA), but the SODA was dropped, and converted to a simple waiver (letter) early in the 2000s.

Research published in 2009 carried out by the City University of London's Applied Vision Research Centre, sponsored by the UK's Civil Aviation Authority and the U.S. Federal Aviation Administration, has established a more accurate assessment of color deficiencies in pilot applicants' red/green and yellow-blue color range which could lead to a 35% reduction in the number of prospective pilots who fail to meet the minimum medical threshold.

Art

Inability to distinguish color does not necessarily preclude the ability to become a celebrated artist. The 20th century expressionist painter Clifton Pugh, three-time winner of Australia's Archibald Prize, on biographical, gene inheritance and other grounds has been identified as a protanope. 19th century French artist Charles Méryon became successful by concentrating on etching rather than painting after he was diagnosed as having a red-green deficiency.

Rights of the color blind

Brazil

A Brazilian court ruled that people with color blindness are protected by the Inter-American Convention on the Elimination of All Forms of Discrimination against Person with Disabilities.

At trial, it was decided that the carriers of color blindness have a right of access to wider knowledge, or the full enjoyment of their human condition.

United States

In the United States, under federal anti-discrimination laws such as the Americans with Disabilities Act, color vision deficiencies have not been found to constitute a disability that triggers protection from workplace discrimination.

A famous traffic light on Tipperary Hill in Syracuse, New York, is upside-down due to the sentiments of its Irish American community, but has been criticized due to the potential hazard it poses for color-blind persons.

Research

Some tentative evidence finds that color blind people are better at penetrating certain color camouflages. Such findings may give an evolutionary reason for the high rate of red–green color blindness. There is also a study suggesting that people with some types of color blindness can distinguish colors that people with normal color vision are not able to distinguish. In World War II, color blind observers were used to penetrate camouflage.

In September 2009, the journal Nature reported that researchers at the University of Washington and University of Florida were able to give trichromatic vision to squirrel monkeys, which normally have only dichromatic vision, using gene therapy.

In 2003, a cybernetic device called eyeborg was developed to allow the wearer to hear sounds representing different colors. Achromatopsic artist Neil Harbisson was the first to use such a device in early 2004; the eyeborg allowed him to start painting in color by memorizing the sound corresponding to each color. In 2012, at a TED Conference, Harbisson explained how he could now perceive colors outside the ability of human vision.

Down syndrome

From Wikipedia, the free encyclopedia

 

Down syndrome
Synonyms	Down's syndrome, Down's, trisomy 21
A boy with Down syndrome assembling a bookcase
Specialty	Medical genetics, pediatrics
Symptoms	Delayed physical growth, characteristic facial features, mild to moderate intellectual disability
Causes	Third copy of chromosome 21
Risk factors	Older mother
Diagnostic method	Prenatal screening, genetic testing
Treatment	Educational support, sheltered work environment
Prognosis	Life expectancy 50 to 60 (developed world)
Frequency	5.4 million (0.1%)
Deaths	26,500 (2015)

Down syndrome (DS or DNS), also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy of chromosome 21. It is typically associated with physical growth delays, characteristic facial features, and mild to moderate intellectual disability. The average IQ of a young adult with Down syndrome is 50, equivalent to the mental ability of an 8 or 9-year-old child, but this can vary widely.


The parents of the affected individual are typically genetically normal. The probability increases from less than 0.1% in 20-year-old mothers to 3% in those age 45. The extra chromosome is believed to occur by chance, with no known behavioral activity or environmental factor that changes the probability. Down syndrome can be identified during pregnancy by prenatal screening followed by diagnostic testing or after birth by direct observation and genetic testing. Since the introduction of screening, pregnancies with the diagnosis are often terminated. Regular screening for health problems common in Down syndrome is recommended throughout the person's life.

There is no cure for Down syndrome. Education and proper care have been shown to improve quality of life. Some children with Down syndrome are educated in typical school classes, while others require more specialized education. Some individuals with Down syndrome graduate from high school, and a few attend post-secondary education. In adulthood, about 20% in the United States do paid work in some capacity, with many requiring a sheltered work environment. Support in financial and legal matters is often needed. Life expectancy is around 50 to 60 years in the developed world with proper health care.

Down syndrome is one of the most common chromosome abnormalities in humans. It occurs in about one per 1,000 babies born each year. In 2015, Down syndrome was present in 5.4 million individuals and resulted in 27,000 deaths, down from 43,000 deaths in 1990. It is named after John Langdon Down, a British doctor who fully described the syndrome in 1866. Some aspects of the condition were described earlier by Jean-Étienne Dominique Esquirol in 1838 and Édouard Séguin in 1844. In 1959, the genetic cause of Down syndrome, an extra copy of chromosome 21, was discovered.

Signs and symptoms

A drawing of the facial features of a baby with Down syndrome

 

An eight-year-old boy with Down syndrome

Those with Down syndrome nearly always have physical and intellectual disabilities. As adults, their mental abilities are typically similar to those of an 8- or 9-year-old. They also typically have poor immune function and generally reach developmental milestones at a later age. They have an increased risk of a number of other health problems, including congenital heart defect, epilepsy, leukemia, thyroid diseases, and mental disorders.

Characteristics	Percentage	Characteristics	Percentage
Mental impairment	99%	Abnormal teeth	60%
Stunted growth	90%	Slanted eyes	60%
Umbilical hernia	90%	Shortened hands	60%
Increased skin back of neck	80%	Short neck	60%
Low muscle tone	80%	Obstructive sleep apnea	60%
Narrow roof of mouth	76%	Bent fifth finger tip	57%
Flat head	75%	Brushfield spots in the iris	56%
Flexible ligaments	75%	Single transverse palmar crease	53%
Proportionally large tongue	75%	Protruding tongue	47%
Abnormal outer ears	70%	Congenital heart disease	40%
Flattened nose	68%	Strabismus	~35%
Separation of first and second toes	68%	Undescended testicles	20%

Physical

Feet of a boy with Down syndrome

People with Down syndrome may have some or all of these physical characteristics: a small chin, slanted eyes, poor muscle tone, a flat nasal bridge, a single crease of the palm, and a protruding tongue due to a small mouth and relatively large tongue. These airway changes lead to obstructive sleep apnea in around half of those with Down syndrome. Other common features include: a flat and wide face, a short neck, excessive joint flexibility, extra space between big toe and second toe, abnormal patterns on the fingertips and short fingers. Instability of the atlantoaxial joint occurs in about 20% and may lead to spinal cord injury in 1–2%. Hip dislocations may occur without trauma in up to a third of people with Down syndrome.

Growth in height is slower, resulting in adults who tend to have short stature—the average height for men is 154 cm (5 ft 1 in) and for women is 142 cm (4 ft 8 in). Individuals with Down syndrome are at increased risk for obesity as they age. Growth charts have been developed specifically for children with Down syndrome.

Neurological

This syndrome causes about a third of cases of intellectual disability. Many developmental milestones are delayed with the ability to crawl typically occurring around 8 months rather than 5 months and the ability to walk independently typically occurring around 21 months rather than 14 months.

Most individuals with Down syndrome have mild (IQ: 50–69) or moderate (IQ: 35–50) intellectual disability with some cases having severe (IQ: 20–35) difficulties. Those with mosaic Down syndrome typically have IQ scores 10–30 points higher. As they age, people with Down syndrome typically perform worse than their same-age peers.

Commonly, individuals with Down syndrome have better language understanding than ability to speak. Between 10 and 45% have either a stutter or rapid and irregular speech, making it difficult to understand them. Some after 30 years of age may lose their ability to speak.

They typically do fairly well with social skills. Behavior problems are not generally as great an issue as in other syndromes associated with intellectual disability. In children with Down syndrome, mental illness occurs in nearly 30% with autism occurring in 5–10%. People with Down syndrome experience a wide range of emotions. While people with Down syndrome are generally happy, symptoms of depression and anxiety may develop in early adulthood.

Children and adults with Down syndrome are at increased risk of epileptic seizures, which occur in 5–10% of children and up to 50% of adults. This includes an increased risk of a specific type of seizure called infantile spasms. Many (15%) who live 40 years or longer develop Alzheimer disease. In those who reach 60 years of age, 50–70% have the disease.

Senses

Brushfield spots, visible in the irises of a baby with Down syndrome

Hearing and vision disorders occur in more than half of people with Down syndrome. Vision problems occur in 38 to 80%. Between 20 and 50% have strabismus, in which the two eyes do not move together. Cataracts (cloudiness of the lens of the eye) occur in 15%, and may be present at birth. Keratoconus (a thin, cone-shaped cornea) and glaucoma (increased eye pressure) are also more common, as are refractive errors requiring glasses or contacts. Brushfield spots (small white or grayish/brown spots on the outer part of the iris) are present in 38 to 85% of individuals.

Hearing problems are found in 50–90% of children with Down syndrome. This is often the result of otitis media with effusion which occurs in 50–70% and chronic ear infections which occur in 40 to 60%. Ear infections often begin in the first year of life and are partly due to poor eustachian tube function. Excessive ear wax can also cause hearing loss due to obstruction of the outer ear canal. Even a mild degree of hearing loss can have negative consequences for speech, language understanding, and academics. Additionally, it is important to rule out hearing loss as a factor in social and cognitive deterioration. Age-related hearing loss of the sensorineural type occurs at a much earlier age and affects 10–70% of people with Down syndrome.

Heart

The rate of congenital heart disease in newborns with Down syndrome is around 40%. Of those with heart disease, about 80% have an atrioventricular septal defect or ventricular septal defect with the former being more common. Mitral valve problems become common as people age, even in those without heart problems at birth. Other problems that may occur include tetralogy of Fallot and patent ductus arteriosus. People with Down syndrome have a lower risk of hardening of the arteries.

Cancer

Although the overall risk of cancer in DS is not changed, the risk of testicular cancer and certain blood cancers, including acute lymphoblastic leukemia (ALL) and acute megakaryoblastic leukemia (AMKL) is increased while the risk of other non blood cancers are decreased. People with DS are believed to have an increased risk of developing cancers derived from germ cells whether these cancers are blood or non-blood related.

Blood cancers

Cancers of the blood are 10 to 15 times more common in children with Down syndrome. In particular, acute lymphoblastic leukemia is 20 times more common and the megakaryoblastic form of acute myeloid leukemia (acute megakaryoblastic leukemia), is 500 times more common. Acute megakaryoblastic leukemia (AMKL) is a leukemia of megakaryoblasts, the precursors cells to megakaryocytes which form blood platelets. Acute lymphoblastic leukemia in Down syndrome accounts for 1-3% of all childhood cases of ALL. It occurs most often in those older than 9 years or having a white blood cell count greater than 50,000 per microliter and is rare in those younger than 1 year old. ALL in DS tends to have poorer outcomes than other cases of ALL in people without DS.

In Down syndrome, AMKL is typically preceded by transient myeloproliferative disease (TMD), a disorder of blood cell production in which non-cancerous megakaryoblasts with a mutation in the GATA1 gene rapidly divide during the later period of pregnancy. The condition affects 3–10% of babies with Down. While it often spontaneously resolves within 3 months of birth, it can cause serious blood, liver, or other complications. In about 10% of cases, TMD progresses to AMKL during the 3 months to 5 years following its resolution.

Non-blood cancers

People with DS have a lower risk of all major solid cancers including those of lung, breast, cervix, with the lowest relative rates occurring in those aged 50 years or older. This low risk is thought due to an increase in the expression of tumor suppressor genes present on chromosome 21. One exception is testicular germ cell cancer which occurs at a higher rate in DS.

Endocrine

Problems of the thyroid gland occur in 20–50% of individuals with Down syndrome. Low thyroid is the most common form, occurring in almost half of all individuals. Thyroid problems can be due to a poorly or nonfunctioning thyroid at birth (known as congenital hypothyroidism) which occurs in 1% or can develop later due to an attack on the thyroid by the immune system resulting in Graves' disease or autoimmune hypothyroidism. Type 1 diabetes mellitus is also more common.

Gastrointestinal

Constipation occurs in nearly half of people with Down syndrome and may result in changes in behavior. One potential cause is Hirschsprung's disease, occurring in 2–15%, which is due to a lack of nerve cells controlling the colon. Other frequent congenital problems include duodenal atresia, pyloric stenosis, Meckel diverticulum, and imperforate anus. Celiac disease affects about 7–20% and gastroesophageal reflux disease is also more common.

Teeth

Individuals with Down syndrome tend to be more susceptible to gingivitis as well as early, severe periodontal disease, necrotising ulcerative gingivitis, and early tooth loss, especially in the lower front teeth. While plaque and poor oral hygiene are contributing factors, the severity of these periodontal diseases cannot be explained solely by external factors. Research suggests that the severity is likely a result of a weakened immune system. The weakened immune system also contributes to increased incidence of yeast infections in the mouth (from Candida albicans).

Individuals with Down syndrome also tend to have a more alkaline saliva resulting in a greater resistance to tooth decay, despite decreased quantities of saliva, less effective oral hygiene habits, and higher plaque indexes.

Higher rates of tooth wear and bruxism are also common. Other common oral manifestations of Down syndrome include enlarged hypotonic tongue, crusted and hypotonic lips, mouth breathing, narrow palate with crowded teeth, class III malocclusion with an underdeveloped maxilla and posterior crossbite, delayed exfoliation of baby teeth and delayed eruption of adult teeth, shorter roots on teeth, and often missing and malformed (usually smaller) teeth. Less common manifestations include cleft lip and palate and enamel hypocalcification (20% prevalence).

Fertility

Males with Down syndrome usually do not father children, while females have lower rates of fertility relative to those who are unaffected. Fertility is estimated to be present in 30–50% of females. Menopause typically occurs at an earlier age. The poor fertility in males is thought to be due to problems with sperm development; however, it may also be related to not being sexually active. As of 2006, three instances of males with Down syndrome fathering children and 26 cases of females having children have been reported. Without assisted reproductive technologies, around half of the children of someone with Down syndrome will also have the syndrome.

Genetics

Karyotype for trisomy Down syndrome: notice the three copies of chromosome 21

Down syndrome is caused by having three copies of the genes on chromosome 21, rather than the usual two. The parents of the affected individual are typically genetically normal. Those who have one child with Down syndrome have about a 1% risk of having a second child with the syndrome, if both parents are found to have normal karyotypes.

The extra chromosome content can arise through several different ways. The most common cause (about 92–95% of cases) is a complete extra copy of chromosome 21, resulting in trisomy 21.In 1.0 to 2.5% of cases, some of the cells in the body are normal and others have trisomy 21, known as mosaic Down syndrome. The other common mechanisms that can give rise to Down syndrome include: a Robertsonian translocation, isochromosome, or ring chromosome. These contain additional material from chromosome 21 and occur in about 2.5% of cases. An isochromosome results when the two long arms of a chromosome separate together rather than the long and short arm separating together during egg or sperm development.

Trisomy 21

Trisomy 21 (also known by the karyotype 47,XX,+21 for females and 47,XY,+21 for males) is caused by a failure of the 21st chromosome to separate during egg or sperm development (nondisjunction). As a result, a sperm or egg cell is produced with an extra copy of chromosome 21; this cell thus has 24 chromosomes. When combined with a normal cell from the other parent, the baby has 47 chromosomes, with three copies of chromosome 21. About 88% of cases of trisomy 21 result from nonseparation of the chromosomes in the mother, 8% from nonseparation in the father, and 3% after the egg and sperm have merged.

Translocation

The extra chromosome 21 material may also occur due to a Robertsonian translocation in 2–4% of cases. In this situation, the long arm of chromosome 21 is attached to another chromosome, often chromosome 14. In a male affected with Down syndrome, it results in a karyotype of 46XY,t(14q21q). This may be a new mutation or previously present in one of the parents. The parent with such a translocation is usually normal physically and mentally; however, during production of egg or sperm cells, a higher chance of creating reproductive cells with extra chromosome 21 material exists. This results in a 15% chance of having a child with Down syndrome when the mother is affected and a less than 5% probability if the father is affected. The probability of this type of Down syndrome is not related to the mother's age. Some children without Down syndrome may inherit the translocation and have a higher probability of having children of their own with Down syndrome. In this case it is sometimes known as familial Down syndrome.

Mechanism

The extra genetic material present in DS results in overexpression of a portion of the 310 genes located on chromosome 21. This overexpression has been estimated at around 50%. Some research has suggested the Down syndrome critical region is located at bands 21q22.1–q22.3, with this area including genes for amyloid, superoxide dismutase, and likely the ETS2 proto oncogene. Other research, however, has not confirmed these findings. microRNAs are also proposed to be involved.

The dementia which occurs in Down syndrome is due to an excess of amyloid beta peptide produced in the brain and is similar to Alzheimer's disease. This peptide is processed from amyloid precursor protein, the gene for which is located on chromosome 21. Senile plaques and neurofibrillary tangles are present in nearly all by 35 years of age, though dementia may not be present.^[11] Those with DS also lack a normal number of lymphocytes and produce less antibodies which contributes to their increased risk of infection.

Epigenetics

Down syndrome is associated with an increased risk of many chronic diseases that are typically associated with older age such as Alzheimer's disease. The accelerated aging suggest that trisomy 21 increases the biological age of tissues, but molecular evidence for this hypothesis is sparse. According to a biomarker of tissue age known as epigenetic clock, trisomy 21 increases the age of blood and brain tissue (on average by 6.6 years).

Diagnosis

Before birth

When screening tests predict a high risk of Down syndrome, a more invasive diagnostic test (amniocentesis or chorionic villus sampling) is needed to confirm the diagnosis. If Down syndrome occurs in one in 500 pregnancies and the test used has a 5% false-positive rate, this means, of 26 women who test positive on screening, only one will have Down syndrome confirmed. If the screening test has a 2% false-positive rate, this means one of eleven who test positive on screening have a fetus with DS. Amniocentesis and chorionic villus sampling are more reliable tests, but they increase the risk of miscarriage between 0.5 and 1%. The risk of limb problems is increased in the offspring due to the procedure. The risk from the procedure is greater the earlier it is performed, thus amniocentesis is not recommended before 15 weeks gestational age and chorionic villus sampling before 10 weeks gestational age.

Abortion rates

About 92% of pregnancies in Europe with a diagnosis of Down syndrome are terminated. In the United States, termination rates are around 67%, but this rate varied from 61% to 93% among different populations. Rates are lower among women who are younger and have decreased over time. When nonpregnant people are asked if they would have a termination if their fetus tested positive, 23–33% said yes, when high-risk pregnant women were asked, 46–86% said yes, and when women who screened positive are asked, 89–97% say yes.

After birth

The diagnosis can often be suspected based on the child's physical appearance at birth. An analysis of the child's chromosomes is needed to confirm the diagnosis, and to determine if a translocation is present, as this may help determine the risk of the child's parents having further children with Down syndrome. Parents generally wish to know the possible diagnosis once it is suspected and do not wish pity.

Screening

Guidelines recommend screening for Down syndrome to be offered to all pregnant women, regardless of age. A number of tests are used, with varying levels of accuracy. They are typically used in combination to increase the detection rate. None can be definitive, thus if screening is positive, either amniocentesis or chorionic villus sampling is required to confirm the diagnosis. Screening in both the first and second trimesters is better than just screening in the first trimester. The different screening techniques in use are able to pick up 90 to 95% of cases with a false-positive rate of 2 to 5%.

First- and second-trimester screening

Screen	Week of pregnancy when performed	Detection rate	False positive	Description
Combined test	10–13.5 wks	82–87%	5%	Uses ultrasound to measure nuchal translucency in addition to blood tests for free or total beta-hCG and PAPP-A
Quad screen	15–20 wks	81%	5%	Measures the maternal serum alpha-fetoprotein, unconjugated estriol, hCG, and inhibin-A
Integrated test	15–20 wks	94–96%	5%	Is a combination of the quad screen, PAPP-A, and NT
Cell-free fetal DNA	From 10 wks	96–100%	0.3%	A blood sample is taken from the mother by venipuncture and is sent for DNA analysis.

Ultrasound

Ultrasound of fetus with Down syndrome showing a large bladder

 

Enlarged NT and absent nasal bone in a fetus at 11 weeks with Down syndrome

Ultrasound imaging can be used to screen for Down syndrome. Findings that indicate increased risk when seen at 14 to 24 weeks of gestation include a small or no nasal bone, large ventricles, nuchal fold thickness, and an abnormal right subclavian artery, among others. The presence or absence of many markers is more accurate. Increased fetal nuchal translucency (NT) indicates an increased risk of Down syndrome picking up 75–80% of cases and being falsely positive in 6%.

Blood tests

Several blood markers can be measured to predict the risk of Down syndrome during the first or second trimester. Testing in both trimesters is sometimes recommended and test results are often combined with ultrasound results. In the second trimester, often two or three tests are used in combination with two or three of: α-fetoprotein, unconjugated estriol, total hCG, and free βhCG detecting about 60–70% of cases.

Testing of the mother's blood for fetal DNA is being studied and appears promising in the first trimester. The International Society for Prenatal Diagnosis considers it a reasonable screening option for those women whose pregnancies are at a high risk for trisomy 21. Accuracy has been reported at 98.6% in the first trimester of pregnancy. Confirmatory testing by invasive techniques (amniocentesis, CVS) is still required to confirm the screening result.

Management

Efforts such as early childhood intervention, screening for common problems, medical treatment where indicated, a good family environment, and work-related training can improve the development of children with Down syndrome. Education and proper care can improve quality of life. Raising a child with Down syndrome is more work for parents than raising an unaffected child. Typical childhood vaccinations are recommended.

Health screening

Recommended screening

Testing	Children	Adults
Hearing	6 months, 12 months, then yearly	3–5 years
T4 and TSH	6 months, then yearly
Eyes	6 months, then yearly	3–5 years
Teeth	2 years, then every 6 months
Coeliac disease	Between 2 and 3 years of age, or earlier if symptoms occur
Sleep study	3 to 4 years, or earlier if symptoms of obstructive sleep apnea occur
Neck X-rays	Between 3 and 5 years of age

A number of health organizations have issued recommendations for screening those with Down syndrome for particular diseases. This is recommended to be done systematically.

At birth, all children should get an electrocardiogram and ultrasound of the heart. Surgical repair of heart problems may be required as early as three months of age. Heart valve problems may occur in young adults, and further ultrasound evaluation may be needed in adolescents and in early adulthood. Due to the elevated risk of testicular cancer, some recommend checking the person's testicles yearly.

Cognitive development

Hearing aids or other amplification devices can be useful for language learning in those with hearing loss. Speech therapy may be useful and is recommended to be started around 9 months of age. As those with Down syndrome typically have good hand-eye coordination, learning sign language may be possible. Augmentative and alternative communication methods, such as pointing, body language, objects, or pictures, are often used to help with communication. Behavioral issues and mental illness are typically managed with counseling or medications.

Education programs before reaching school age may be useful. School-age children with Down syndrome may benefit from inclusive education (whereby students of differing abilities are placed in classes with their peers of the same age), provided some adjustments are made to the curriculum. Evidence to support this, however, is not very strong. In the United States, the Individuals with Disabilities Education Act of 1975 requires public schools generally to allow attendance by students with Down syndrome.

Individuals with Down syndrome may learn better visually. Drawing may help with language, speech, and reading skills. Children with Down syndrome still often have difficulty with sentence structure and grammar, as well as developing the ability to speak clearly. Several types of early intervention can help with cognitive development. Efforts to develop motor skills include physical therapy, speech and language therapy, and occupational therapy. Physical therapy focuses specifically on motor development and teaching children to interact with their environment. Speech and language therapy can help prepare for later language. Lastly, occupational therapy can help with skills needed for later independence.

Other

Tympanostomy tubes are often needed and often more than one set during the person's childhood. Tonsillectomy is also often done to help with sleep apnea and throat infections. Surgery, however, does not always address the sleep apnea and a continuous positive airway pressure (CPAP) machine may be useful. Physical therapy and participation in physical education may improve motor skills. Evidence to support this in adults, however, is not very good.

Efforts to prevent respiratory syncytial virus (RSV) infection with human monoclonal antibodies should be considered, especially in those with heart problems. In those who develop dementia there is no evidence for memantine, donepezil, rivastigmine, or galantamine.

Plastic surgery has been suggested as a method of improving the appearance and thus the acceptance of people with Down syndrome. It has also been proposed as a way to improve speech. Evidence, however, does not support a meaningful difference in either of these outcomes. Plastic surgery on children with Down syndrome is uncommon, and continues to be controversial. The U.S. National Down Syndrome Society views the goal as one of mutual respect and acceptance, not appearance.

Many alternative medical techniques are used in Down syndrome; however, they are poorly supported by evidence. These include: dietary changes, massage, animal therapy, chiropractic and naturopathy, among others. Some proposed treatments may also be harmful.

Prognosis

Deaths due to Down syndrome per million persons in 2012 

 

  0–0

  1–1

  2–2

  3–3

  4–4

  5–5

  6–6

  7–8

  9–16

Between 5 and 15% of children with Down syndrome in Sweden attend regular school. Some graduate from high school; however, most do not. Of those with intellectual disability in the United States who attended high school about 40% graduated. Many learn to read and write and some are able to do paid work. In adulthood about 20% in the United States do paid work in some capacity. In Sweden, however, less than 1% have regular jobs. Many are able to live semi-independently, but they often require help with financial, medical, and legal matters. Those with mosaic Down syndrome usually have better outcomes.

Individuals with Down syndrome have a higher risk of early death than the general population. This is most often from heart problems or infections. Following improved medical care, particularly for heart and gastrointestinal problems, the life expectancy has increased. This increase has been from 12 years in 1912, to 25 years in the 1980s, to 50 to 60 years in the developed world in the 2000s. Currently between 4 and 12% die in the first year of life. The probability of long-term survival is partly determined by the presence of heart problems. In those with congenital heart problems 60% survive to 10 years and 50% survive to 30 years of age. In those without heart problems 85% survive to 10 years and 80% survive to 30 years of age. About 10% live to 70 years of age. The National Down Syndrome Society have developed information regarding the positive aspects of life with Down syndrome.

Epidemiology

The risk of having a Down syndrome pregnancy in relation to a mother's age

Globally, as of 2010, Down syndrome occurs in about 1 per 1000 births and results in about 17,000 deaths. More children are born with Down syndrome in countries where abortion is not allowed and in countries where pregnancy more commonly occurs at a later age. About 1.4 per 1000 live births in the United States and 1.1 per 1000 live births in Norway are affected. In the 1950s, in the United States, it occurred in 2 per 1000 live births with the decrease since then due to prenatal screening and abortions. The number of pregnancies with Down syndrome is more than two times greater with many spontaneously aborting. It is the cause of 8% of all congenital disorders.

Maternal age affects the chances of having a pregnancy with Down syndrome. At age 20, the chance is one in 1441; at age 30, it is one in 959; at age 40, it is one in 84; and at age 50 it is one in 44. Although the probability increases with maternal age, 70% of children with Down syndrome are born to women 35 years of age and younger, because younger people have more children. The father's older age is also a risk factor in women older than 35, but not in women younger than 35, and may partly explain the increase in risk as women age.

History

It has been suggested that this Early Netherlandish painting depicts a person with Down syndrome as one of the angels.

English physician John Langdon Down first described Down syndrome in 1862, recognizing it as a distinct type of mental disability, and again in a more widely published report in 1866. Édouard Séguin described it as separate from cretinism in 1844. By the 20th century, Down syndrome had become the most recognizable form of mental disability.

In antiquity, many infants with disabilities were either killed or abandoned. A number of historical pieces of art are believed to portray Down syndrome, including pottery from the pre-Columbian Tumaco-La Tolita culture in present-day Colombia and Ecuador, and the 16th-century painting The Adoration of the Christ Child.

In the 20th century, many individuals with Down syndrome were institutionalized, few of the associated medical problems were treated, and most died in infancy or early adult life. With the rise of the eugenics movement, 33 of the then 48 U.S. states and several countries began programs of forced sterilization of individuals with Down syndrome and comparable degrees of disability. Action T4 in Nazi Germany made public policy of a program of systematic involuntary euthanization.

With the discovery of karyotype techniques in the 1950s, it became possible to identify abnormalities of chromosomal number or shape. In 1959, Jérôme Lejeune reported the discovery that Down syndrome resulted from an extra chromosome. However, Lejeune's claim to the discovery has been disputed, and in 2014, the Scientific Council of the French Federation of Human Genetics unanimously awarded its Grand Prize to his colleague Marthe Gautier for her role in this discovery. The discovery was in the laboratory of Raymond Turpin at the Hôpital Trousseau in Paris, France. Jérôme Lejeune and Marthe Gautier were both his students.

As a result of this discovery, the condition became known as trisomy 21. Even before the discovery of its cause, the presence of the syndrome in all races, its association with older maternal age, and its rarity of recurrence had been noticed. Medical texts had assumed it was caused by a combination of inheritable factors that had not been identified. Other theories had focused on injuries sustained during birth.

Society and culture

Name

Due to his perception that children with Down syndrome shared facial similarities with those of Blumenbach's Mongolian race, John Langdon Down used the term "mongoloid". He felt that the existence of Down syndrome confirmed that all peoples were genetically related. In the 1950s with discovery of the underlying cause as being related to chromosomes, concerns about the race-based nature of the name increased.

In 1961, 19 scientists suggested that "mongolism" had "misleading connotations" and had become "an embarrassing term". The World Health Organization (WHO) dropped the term in 1965 after a request by the delegation from the Mongolian People's Republic. While the term mongoloid (also mongolism, Mongolian imbecility or idiocy) continued to be used until the early 1980s, it is now considered unacceptable and is no longer in common use.

In 1975, the United States National Institutes of Health (NIH) convened a conference to standardize the naming and recommended replacing the possessive form, "Down's syndrome" with "Down syndrome". However, both the possessive and nonpossessive forms remain in use by the general population. The term "trisomy 21" is also commonly used.

Ethics

Father with son who has Down syndrome

Some obstetricians argue that not offering screening for Down syndrome is unethical. As it is a medically reasonable procedure, per informed consent, people should at least be given information about it. It will then be the woman's choice, based on her personal beliefs, how much or how little screening she wishes. When results from testing become available, it is also considered unethical not to give the results to the person in question.

Some bioethicists deem it reasonable for parents to select a child who would have the highest well-being. One criticism of this reasoning is that it often values those with disabilities less. Some parents argue that Down syndrome shouldn't be prevented or cured and that eliminating Down syndrome amounts to genocide. The disability rights movement does not have a position on screening, although some members consider testing and abortion discriminatory. Some in the United States who are pro-life support abortion if the fetus is disabled, while others do not. Of a group of 40 mothers in the United States who have had one child with Down syndrome, half agreed to screening in the next pregnancy.

Within the US, some Protestant denominations see abortion as acceptable when a fetus has Down syndrome, while Orthodox Christians and Roman Catholics often do not. Some of those against screening refer to it as a form of "eugenics". Disagreement exists within Islam regarding the acceptability of abortion in those carrying a fetus with Down syndrome. Some Islamic countries allow abortion, while others do not. Women may face stigmatization whichever decision they make.

Advocacy groups

Advocacy groups for individuals with Down syndrome began to be formed after the Second World War. These were organizations advocating for the inclusion of people with Down syndrome into the general school system and for a greater understanding of the condition among the general population, as well as groups providing support for families with children living with Down syndrome. Before this individuals with Down syndrome were often placed in mental hospitals or asylums. Organizations included the Royal Society for Handicapped Children and Adults founded in the UK in 1946 by Judy Fryd, Kobato Kai founded in Japan in 1964, the National Down Syndrome Congress founded in the United States in 1973 by Kathryn McGee and others, and the National Down Syndrome Society founded in 1979 in the United States.

The first World Down Syndrome Day was held on 21 March 2006. The day and month were chosen to correspond with 21 and trisomy, respectively. It was recognized by the United Nations General Assembly in 2011.

Research

Efforts are underway to determine how the extra chromosome 21 material causes Down syndrome, as currently this is unknown, and to develop treatments to improve intelligence in those with the syndrome. One hope is to use stem cells. Other methods being studied include the use of antioxidants, gamma secretase inhibition, adrenergic agonists, and memantine. Research is often carried out on an animal model, the Ts65Dn mouse.