Heterochromia iridum

Heterochromia
Complete heterochromia in human eyes: one brown and one green/hazel
Classification and external resources
Specialty	ophthalmology
ICD-10	Q13.2, H20.8, L67.1
ICD-9-CM	364.53
OMIM	142500
DiseasesDB	31289
MedlinePlus	003319
MeSH	C538115

In anatomy, heterochromia (ancient Greek: ἕτερος, héteros, different + χρώμα, chróma, color^[1]) is a difference in coloration, usually of the iris but also of hair or skin. Heterochromia is a result of the relative excess or lack of melanin (a pigment). It may be inherited, or caused by genetic mosaicism, chimerism, disease, or injury.^[2]

Heterochromia of the eye (heterochromia iridis or heterochromia iridum) is of three kinds. In complete heterochromia, one iris is a different color from the other. In sectoral heterochromia, part of one iris is a different color from its remainder and finally in "central heterochromia" there are spikes of different colours radiating from the pupil.

Though multiple causes have been posited, the scientific consensus is that inbreeding is the primary reason behind heterochromia. This is due to mutation of the genes that determine melanin distribution at the 8-HTP pathway, which usually only become corrupted due to chromosomal homogeneity.^[3]

Eye color, specifically the color of the irises, is determined primarily by the concentration and distribution of melanin.^[4][5] The affected eye may be hyperpigmented (hyperchromic) or hypopigmented (hypochromic).^[3] In humans, usually, an excess of melanin indicates hyperplasia of the iris tissues, whereas a lack of melanin indicates hypoplasia.

Classification

Congenital heterochromia: inherited in autosomal dominant fashion (from men or women)

Heterochromia is classified primarily by onset: as either genetic or acquired. Although a distinction is frequently made between heterochromia that affects an eye completely or only partially (sectoral heterochromia), it is often classified as either genetic (due to mosaicism or congenital) or acquired, with mention as to whether the affected iris or portion of the iris is darker or lighter.^[6] Most cases of heterochromia are hereditary, caused by a disease or syndrome, or due to an injury. Sometimes one eye may change color following certain diseases or injuries.^[7]

Congenital heterochromia

Heterochromia that is congenital is usually inherited as an autosomal dominant trait.

Sectoral heterochromia

In sectoral heterochromia, the iris contains two completely different colors in the same area. Sectoral heterochromia looks like an irregular spot that is a different color than the eye color and does not form a complete ring around the pupil like central heterochromia.

Heterochromia is most prevalent in cats and dogs. Sectoral heterochromia is extremely rare in humans; only about 1% of the population has it.

Abnormal iris darker

• Lisch nodules – iris hamartomas seen in neurofibromatosis.
• Ocular melanosis – a condition characterized by increased pigmentation of the uveal tract, episclera, and anterior chamber angle.
• Oculodermal melanocytosis (nevus of Ota)^[3]
• Pigment dispersion syndrome – a condition characterized by loss of pigmentation from the posterior iris surface which is disseminated intraocularly and deposited on various intraocular structures, including the anterior surface of the iris.
• Sturge-Weber syndrome – a syndrome characterized by a port-wine stain nevus in the distribution of the trigeminal nerve, ipsilateral leptomeningeal angiomas with intracranial calcification and neurologic signs, and angioma of the choroid, often with secondary glaucoma.^[8][9]

Abnormal iris lighter

Individual with Waardenburg Syndrome Type II exhibiting complete heterochromia iridum

• Simple heterochromia – a rare condition characterized by the absence of other ocular or systemic problems. The lighter eye is typically regarded as the affected eye as it usually shows iris hypoplasia. It may affect an iris completely or only partially.
• Congenital Horner's syndrome^[10] – sometimes inherited, although usually acquired
• Waardenburg syndrome^[10] – a syndrome in which heterochromia is expressed as a bilateral iris hypochromia in some cases. A Japanese review of 11 albino children with the disorder found that all had sectoral/partial heterochromia.^[11]
• Piebaldism – similar to Waardenburg's syndrome, a rare disorder of melanocyte development characterized by a white forelock and multiple symmetrical hypopigmented or depigmented macules.
• Hirschsprung's disease – a bowel disorder associated with heterochromia in the form of a sector hypochromia. The affected sectors have been shown to have reduced numbers of melanocytes and decreased stromal pigmentation.^[12]
• Incontinentia pigmenti^[3]
• Parry-Romberg syndrome^[3]

Acquired heterochromia

Heterochromia that is acquired is usually due to injury, inflammation, the use of certain eyedrops that damages the iris,^[13] or tumors.

Abnormal iris darker

• Deposition of material
  • Siderosis – iron deposition within ocular tissues due to a penetrating injury and a retained iron-containing, intraocular foreign body.
  • Hemosiderosis – long standing hyphema (blood in the anterior chamber) following blunt trauma to the eye may lead to iron deposition from blood products
• Certain eyedrops – prostaglandin analogues (latanoprost, isopropyl unoprostone, travoprost, and bimatoprost) are used topically to lower intraocular pressure in glaucoma patients. A concentric heterochromia has developed in some patients applying these drugs. The stroma around the iris sphincter muscle becomes darker than the peripheral stroma. A stimulation of melanin synthesis within iris melanocytes has been postulated.
• Neoplasm – Nevi and melanomatous tumors.
• Iridocorneal endothelium syndrome^[3]
• Iris ectropion syndrome^[3]

Abnormal iris lighter

• Fuchs heterochromic iridocyclitis – a condition characterized by a low grade, asymptomatic uveitis in which the iris in the affected eye becomes hypochromic and has a washed-out, somewhat moth eaten appearance. The heterochromia can be very subtle, especially in patients with lighter colored irides. It is often most easily seen in daylight. The prevalence of heterochromia associated with Fuchs has been estimated in various studies^[14][15][16] with results suggesting that there is more difficulty recognizing iris color changes in dark-eyed individuals.^[16][17]
• Acquired Horner's syndrome – usually acquired, as in neuroblastoma,^[18] although sometimes inherited.
• Neoplasm – Melanomas can also be very lightly pigmented, and a lighter colored iris may be a rare manifestation of metastatic disease to the eye.

Heterochromia has also been observed in those with Duane syndrome.^[19][20]

• Chronic iritis^[3]
• Juvenile xanthogranuloma^[3]
• Leukemia and lymphoma^[3]

Central heterochromia

Example of central heterochromia showing a gold to blue iris

Central heterochromia example

Central heterochromia is an eye condition where there are two colors in the same iris; the central (pupillary) zone of the iris is a different color than the mid-peripheral (ciliary) zone, with the true iris color being the outer color. ^[21]

Eye color is determined primarily by the concentration and distribution of melanin within the iris tissues. Although the processes determining eye color are not fully understood, it is known that inherited eye color is determined by multiple genes. Environmental or acquired factors can alter these inherited traits.^[4]

The human iris can be seen in a number of various colors. There are three true colors in human eyes that determine the outward appearance: brown, yellow, and grey. The amount of each color an individual has determines the appearance of the eye color.^[22]

Eyes displaying central heterochromia are often referred to as "cat eyes" because of their multi-colored iris. Central heterochromia appears to be prevalent in irises containing low amounts of melanin.^[23]

A famous case of a person with central heterochromia was Baroness Rozsika Edle von Wertheimstein, whose daughter wrote: "She was a very beautiful woman... She had dark, dark brown eyes, but each eye had a purple ring to it, about a quarter of an inch of purple around these dark brown eyes."^[24]

In other organisms

Although infrequently seen in humans, complete heterochromia is more frequently observed in other species, where it almost always involves one blue eye. The blue eye occurs within a white spot, where melanin is absent from the skin and hair (see Leucism). These species include the cat, particularly breeds such as Turkish Van, Turkish Angora, Khao Manee and (rarely) Japanese Bobtail. These so-called odd-eyed cats are white, or mostly white, with one normal eye (copper, orange, yellow, green), and one blue eye. Among dogs, complete heterochromia is seen often in the Siberian Husky and few other breeds, usually Australian Shepherd and Catahoula Leopard Dog and rarely in Shih Tzu. Horses with complete heterochromia have one brown and one white, gray, or blue eye—complete heterochromia is more common in horses with pinto coloring. Complete heterochromia occurs also in cattle and even water buffalo.^[25] It can also be seen in ferrets with Waardenburg Syndrome, although it can be very hard to tell at times as the eye color is often a midnight blue.

Sectoral heterochromia, usually sectoral hypochromia, is often seen in dogs, specifically in breeds with merle coats. These breeds include the Australian Shepherd, Border Collie, Collie, Shetland Sheepdog, Welsh Corgi, Pyrenean Shepherd, Mudi, Beauceron, Catahoula Cur, Dunker, Great Dane, Dachshund and Chihuahua. It also occurs in certain breeds that do not carry the merle trait, such as the Siberian Husky and rarely, Shih Tzu. There are example of cat breeds that have the condition such as Van cat.

Gallery

• 

  Complete heterochromia in a teenager who also has anisocoria.

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  A young adult exhibiting sectoral heterochromia in the form of an orange segment in her right, blue eye. The individual's mother exhibited a similar orange segment in her left eye, although her iris color was green.

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  Heterochromia in a child.

• 

  Norwegian forest cat with heterochromia. One blue, and one green. The blue one has sectoral heterochromia, as there is a bit of green in the top of the iris.

• 

  Complete heterochromia in a cat: one eye blue, one yellow. The yellow eye has what looks like central heterochromia, as the outside of the eye is yellow, and the iris is green.

• 

  Complete heterochromia in a Siberian Husky: one eye blue, one eye brown.

• 

  Sectoral hypochromia in a blue merle Border Collie.

• 

  A cat with complete heterochromia.

• 

  Example of central heterochromia showing an orange to blue iris.

• 

  An example of a hazel eye with a brown section.

See also

References

External links

Wikimedia Commons has media related to Heterochromia.

• Photograph of Radial Reddish Sunburst Pattern in Right Eye of Bluish Hazel Eyed Woman