Heterochromia is a variation in coloration. The term is most often used to describe color differences of the iris, but can also be applied to color variation of

hair Hair is a protein filament that grows from follicles found in the dermis. Hair is one of the defining characteristics of mammals. The human body, apart from areas of glabrous skin, is covered in follicles which produce thick terminal and f ...

or skin. Heterochromia is determined by the production, delivery, and concentration of melanin (a pigment). It may be inherited, or caused by genetic mosaicism,

chimerism A genetic chimerism or chimera ( ) is a single organism composed of cells with more than one distinct genotype. In animals, this means an individual derived from two or more zygotes, which can include possessing blood cells of different blood ty ...

, disease, or

injury An injury is any physiological damage to living tissue caused by immediate physical stress. An injury can occur intentionally or unintentionally and may be caused by blunt trauma, penetrating trauma, burning, toxic exposure, asphyxiation, o ...

. It occurs in humans and certain breeds of domesticated animals. Heterochromia of the

eye Eyes are organs of the visual system. They provide living organisms with vision, the ability to receive and process visual detail, as well as enabling several photo response functions that are independent of vision. Eyes detect light and conv ...

is called heterochromia iridum or heterochromia iridis. It can be complete or sectoral. 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. In central heterochromia, there is a ring around the pupil or possibly spikes of different colors radiating from the pupil. Though multiple causes have been posited, the scientific consensus is that a lack of

genetic diversity Genetic diversity is the total number of genetic characteristics in the genetic makeup of a species, it ranges widely from the number of species to differences within species and can be attributed to the span of survival for a species. It is dis ...

is the primary reason behind heterochromia, at least in domestic animals. This is due to a mutation of the genes that determine melanin distribution at the 8-HTP pathway, which usually only become corrupted due to chromosomal homogeneity. Though common in some breeds of cats, dogs, cattle and horses due to inbreeding, heterochromia is uncommon in humans, affecting fewer than 200,000 people in the United States, and is not associated with lack of genetic diversity. The affected eye may be hyperpigmented (hyperchromic) or hypopigmented (hypochromic). In humans, an increase of melanin production in the eyes indicates

hyperplasia Hyperplasia (from ancient Greek ὑπέρ ''huper'' 'over' + πλάσις ''plasis'' 'formation'), or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of organic tissue that results from cell proliferati ...

of the iris tissues, whereas a lack of melanin indicates

Background

Eye color, specifically the color of the irises, is determined primarily by the concentration and distribution of melanin. Although the processes determining eye color are not fully understood, it is known that inherited eye color is determined by multiple

genes In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

. Environmental or acquired factors can alter these inherited traits. The color of the mammalian, including human, iris is very variable. However, there are only two pigments present,

eumelanin Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amin ...

and pheomelanin. The overall concentration of these pigments, the ratio between them, variation in the distribution of pigment in the layers of the stroma of the iris and the effects of light scattering all play a part in determining eye color.

Classification

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 A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can ...

) or acquired, with mention as to whether the affected iris or portion of the iris is darker or lighter.Swann P
"Heterochromia."
''Optometry Today.'' January 29, 1999. Retrieved November 1, 2006. Most cases of heterochromia are hereditary, or caused by genetic factors such as chimerism, and are entirely benign and unconnected to any pathology, however, some are associated with certain diseases and syndromes. Sometimes one eye may change color following disease or injury.

Genetic

Abnormal iris darker

* Lisch nodules – iris hamartomas seen in

neurofibromatosis Neurofibromatosis (NF) is a group of three conditions in which tumors grow in the nervous system. The three types are neurofibromatosis type I (NF1), neurofibromatosis type II Neurofibromatosis type II (also known as MISME syndrome – multi ...

. * Ocular melanosis – a condition characterized by increased pigmentation of the uveal tract, episclera, and anterior chamber angle. * Oculodermal melanocytosis (nevus of Ota) * 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.

Abnormal iris lighter

*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 Hypoplasia (from Ancient Greek ὑπo- ''hypo-'' 'under' + πλάσις ''plasis'' 'formation'; adjective form ''hypoplastic'') is underdevelopment or incomplete development of a tissue or organ.Congenital Horner's syndrome Horner's syndrome, also known as oculosympathetic paresis, is a combination of symptoms that arises when a group of nerves known as the sympathetic trunk is damaged. The signs and symptoms occur on the same side (ipsilateral) as it is a lesion ...

– sometimes inherited, although usually acquired. * Waardenburg syndrome – a syndrome in which heterochromia is expressed as a bilateral iris hypochromia in some cases. A Japanese review of 11 children with albinism found that the condition was present. All had sectoral/partial heterochromia. * 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. * Incontinentia pigmenti *

Parry–Romberg syndrome Parry–Romberg syndrome (PRS) is a rare disease characterized by progressive shrinkage and degeneration of the tissues beneath the skin, usually on only one side of the face (hemifacial atrophy) but occasionally extending to other parts of th ...

Acquired

Acquired heterochromia is usually due to injury, inflammation, the use of certain eyedrops that damage the iris, 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. A stimulation of melanin synthesis within iris melanocytes has been postulated. * Neoplasm – Nevi and melanomatous tumors. *Iridocorneal endothelium syndrome *Iris ectropion syndrome

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 with results suggesting that there is more difficulty recognizing iris color changes in dark-eyed individuals. * Acquired Horner's syndrome – usually acquired, as in neuroblastoma, although sometimes inherited. * Neoplasm –

Melanoma Melanoma, also redundantly known as malignant melanoma, is a type of skin cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye ( ...

s can also be very lightly pigmented, and a lighter colored iris may be a rare manifestation of metastatic disease to the eye. *

– due to tissue loss. Heterochromia has also been observed in those with Duane syndrome. *Chronic iritis *Juvenile

xanthogranuloma Juvenile xanthogranuloma is a form of histiocytosis, classified as "non-Langerhans cell histiocytosis", or more specifically, "type 2". It is a rare skin disorder that primarily affects children under one year of age but can also be found in olde ...

* Leukemia and lymphoma

Partial heterochromia – different colors in the same iris

Partial heterochromia is most often a benign trait of genetic origins, but, like complete heterochromia, can be acquired or be related to clinical syndromes. Sectoral heterochromia in left eye

Sectoral

In sectoral heterochromia, areas of the same iris contain two different colors, the contrasting colors being demarcated in a radial, or sectoral, manner. Sectoral heterochromia may affect one or both eyes. It is unknown how rare sectoral heterochromia is in humans, but it is considered to be less common than complete heterochromia.

Central

Central heterochromia is also an eye condition where there are two colors in the same iris; but the arrangement is concentric, rather than sectoral. The central (pupillary) zone of the iris is a different color than the mid-peripheral (ciliary) zone. Central heterochromia is more noticeable in irises containing low amounts of melanin.

In history and culture

Heterochromia of the eye was first described as a human condition by Aristotle, who termed it ''heteroglaucos''. Notable historical figures thought to have heterochromia include the Byzantine emperor Anastasius the First, dubbed ''dikoros'' (Greek for 'having two pupils'). "His right eye was light blue, while the left was black, nevertheless his eyes were most attractive", is the description of the historian

John Malalas John Malalas ( el, , ''Iōánnēs Malálas''; – 578) was a Byzantine chronicler from Antioch (now Antakya, Turkey). Life Malalas was of Syrian descent, and he was a native speaker of Syriac who learned how to write in Greek later in ...

. A more recent example is the German poet, playwright, novelist, scientist, statesman, theatre director, and critic,

Johann Wolfgang Goethe Johann Wolfgang von Goethe (28 August 1749 – 22 March 1832) was a German poet, playwright, novelist, scientist, statesman, theatre director, and critic. His works include plays, poetry, literature, and aesthetic criticism, as well as treatis ...

. The '' Alexander Romance'', an early literary treatment of the life of Alexander the Great, attributes heterochromia to him. In it he is described as having one eye light and one eye dark. However, no ancient historical source mentions this. It is used to emphasise the otherworldly and heroic qualities of Alexander. In the

Ars Amatoria The ''Ars amatoria'' ( en, The Art of Love) is an instructional elegy series in three books by the ancient Roman poet Ovid. It was written in 2 AD. Background Book one of ''Ars amatoria'' was written to show a man how to find a woman. In book two ...

, the Roman poet Ovid describes the witch Dipsas as having 'double pupils'. Kirby Flower Smith suggested that this could be understood as heterochromia, though other scholars have disagreed. The Roman jurist and writer Cicero also mentions the same feature of 'double pupils' as being found in some Italic women. Pliny the Elder related this feature to the concept of 'the evil eye'. The twelfth-century scholar Eustathius, in his commentary on the Iliad, reports a tradition in which the Thracian Thamyris (son of the nymph Argiope), who was famed for his musical abilities, had one eye that was grey, whilst the other was black. W. B. McDaniel suggests that this should be interpreted as heterochromia.

In other animals

Although infrequently seen in humans, complete heterochromia is more frequently observed in species of domesticated mammals. 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 The Turkish Van (pronounced Von) is a naturally occurring breed of domestic cat that originated in the Lake Van area of modern-day Turkey, part of Armenian Highlands. The Van is classified as a semi-long hair, but it has two lengths of hair, de ...

, Turkish Angora, Khao Manee and (rarely)

Japanese Bobtail The Japanese Bobtail is a breed of domestic cat with an unusual bobtail more closely resembling the tail of a rabbit than that of other cats. The variety is native to Japan, though it is now found throughout the world. The breed has been know ...

. These so-called

odd-eyed cat An odd-eyed cat is a cat with one blue eye and one eye either green, yellow, or brown. This is a feline form of complete heterochromia,Foster, Race and Smith, Marty, ( DVMs)Heterochromia, A-Z Health Library, Purina-One. Retrieved February 2007 ...

s 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 Pinto is a Portuguese language, Portuguese, Spanish language, Spanish, Sephardi Jews, Jewish (Sephardic), and Italian language, Italian surname. It is a high-frequency surname in all List of countries and territories where Portuguese is an officia ...

coloring. Complete heterochromia occurs also in cattle and even water buffalo. 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 Merle may refer to: People *Merle (given name), a given name used by both men and women *Merle (surname), a surname of French origin Others *Merle (dog coat), a pattern in dogs’ coats *Merle (grape), another name for the wine grape Merlot *Akaf ...

coats. These breeds include the Australian Shepherd, Border Collie, Collie, Shetland Sheepdog, Welsh Corgi,

Pyrenean Shepherd The Pyrenean Sheepdog, the Chien de Berger des Pyrénées in French, is a small to medium-sized breed of herding dog from the Pyrenees Mountains region of France. It is found herding flocks of sheep throughout the Pyrenees alongside the much larger ...

, Mudi, Beauceron, Catahoula Cur, Dunker, Great Dane,

Dachshund The dachshund ( or ; German: "badger dog"), also known as the wiener dog, badger dog, and sausage dog, is a short-legged, long-bodied, hound-type dog breed. The dog may be smooth-haired, wire-haired, or long-haired, and comes in a variety of c ...

and

Chihuahua Chihuahua may refer to: Places *Chihuahua (state), a Mexican state **Chihuahua (dog), a breed of dog named after the state **Chihuahua cheese, a type of cheese originating in the state **Chihuahua City, the capital city of the state **Chihuahua Mun ...

. It also occurs in certain breeds that do not carry the merle trait, such as the Siberian Husky and rarely, Shih Tzu. There are examples of cat breeds that have the condition such as

Van cat The Van cat ( tr, Van kedisi; ; Eastern ; ku, pisîka Wanê, script=Latn, italic=yes) is a distinctive landrace of the domestic cat found in the Lake Van area of the Armenian Highlands in Turkey. Van cats are relatively large, have a chal ...

Gallery

File:Heterochromia Iridis.jpg, Complete heterochromia in a child. File:Sectoral Heterochromia5600.jpg, A young adult human exhibiting sectoral heterochromia in the form of an orange-brown segment in blue eye. File:Heterochromia Blue Orange.png, Human eye with central heterochromia showing an orange-brown to blue iris. File:Alice Eve, Men in Black 3, 2012 (crop).jpg, Actress Alice Eve has heterochromia: her left eye is blue and right eye is green. File:Shane Warne February 2015.jpg, Australian cricketer Shane Warne had complete heterochromia: his left eye was green and right eye was blue. File:Anouchka Delon 2014.jpg, Actress

Anouchka Delon Anouchka Delon (born 25 November 1990) is a French-Dutch actress. Early life Delon is the daughter of Alain Delon and Rosalie van Breemen. She has a younger brother, Alain-Fabien Delon, and two older half-brothers, Christian Aaron "Ari" Bo ...

: brown and blue File:Nationals pitcher Max Scherzer talks to reporters at 2016 All-Star Game availability. (28232354950).jpg, Professional baseball pitcher Max Scherzer has complete heterochromia: his right eye is blue and his left eye is brown. File:Kate Bosworth Deauville 2011.jpg, Actress Kate Bosworth has complete heterochromia: her left eye is blue and her right eye is hazel. File:Dominic Sherwood (22429006997).jpg, Actor

Dominic Sherwood Dominic Anthony Sherwood (born 6 February 1990) is an English actor and model, best known for his roles as Christian Ozera in the teen vampire film ''Vampire Academy'' (2014), Jace Wayland on the Freeform fantasy series ''Shadowhunters'' (2016- ...

has sectoral heterochromia. File:Henry Cavill-2665842.jpg, Actor Henry Cavill has sectoral heterochromia. File:Heterochromia sled dog.jpg, Complete heterochromia in a female sled dog File:Husky pysk 89.jpg, Complete heterochromia in a Siberian Husky: one eye blue, one eye brown. File:DogEye2color cr wb.jpg, Sectoral hypochromia in a blue merle Border Collie. File:Heterochromia in a mutt dog.jpg, Sectoral heterochromia in a mutt dog. File:Angoraturco.jpg, A Turkish Angora cat with complete heterochromia. File:Central heterochromia cat.jpg, Central heterochromia in a bicolor tabby cat.

Misattribution

English singer David Bowie exhibited

anisocoria Anisocoria is a condition characterized by an unequal size of the eyes' pupils. Affecting up to 20% of the population, anisocoria is often entirely harmless, but can be a sign of more serious medical problems. Causes Anisocoria is a common condit ...

(one pupil was larger than the other), owing to a teenage injury. This was sometimes mistaken for heterochromia iridum.

References

External links

''Photograph of Radial Reddish Sunburst Pattern in Right Eye of Bluish Hazel Eyed Woman''
{{Medicine Disturbances of pigmentation Eye color Eye diseases Genodermatoses Medical signs

Background

Classification

Genetic

Abnormal iris darker

Abnormal iris lighter

Acquired

Abnormal iris darker

Abnormal iris lighter

Partial heterochromia – different colors in the same iris

Sectoral

Central

In history and culture

In other animals

Gallery

Misattribution

See also

References

External links