V. Kockler, MD


 A 6-month-old boy with different colored eyes since   birth. The parents are concerned that the eye anomaly   may be associated with an underlying condition after   reading about eye disorders online. They think the color   of the eyes may have darkened slightly but have not noticed   an unequal appearance to the pupils or drooping of   either upper eyelid. No family members, including an   older brother, have similar eye discoloration. There is no   history of consanguinity. Otherwise healthy infant with   normal stools and no chronic diarrhea. Prenatal and   postnatal histories uneventful, developmental milestones   appropriate. No history of prenatal maternal infections or   perinatal trauma. Results of newborn hearing screen normal,   no hearing problems subsequently reported.


 Happy infant with stable vital signs. Physical findings   and growth parameters essentially within normal   limits for age. Ocular examination reveals normal lids   and lashes, with no ptosis, bruising, or port-wine stains.   Conjunctiva is white, with no corkscrew vessels. Cornea   is clear; anterior chamber is deep and appears quiet.   Right iris has dark brown pigmentation except for the   area between the 6 and 8 o’clock position, which is bluegray   and sharply demarcated. Iris architecture appears   normal, although the iris crypts are less visible in the   darker brown area of the right eye on close examination.   Left iris is blue-gray at the periphery and hazelbrown   centrally near the pupil. Remaining ocular findings   normal. Extraocular movements intact in all directions.   Both pupils dilate equally in the dark and constrict   equally in response to light.

Heterochromia of the iris is relatively uncommon and may be congenital or acquired. This child has congenital heterochromia, which is usually inherited as an autosomal dominant trait but may be seen in mosaicism, or rarely in chimerism. In isolated cases, it has no medical significance, and otherwise healthy patients can be reassured of its benign prognosis.


 Heterochromia iridis can be described as complete   or partial.1 Partial heterochromia may be further classified   as central or sectoral. In complete heterochromia,   one eye is lighter than the other because of a decreased   number of pigment granules in the iris stroma. In partial   heterochromia, one portion of the iris is a different   color from the rest of the iris. In central heterochromia   (this patient’s left eye), the peripheral portion of the iris   is lightly pigmented while the central area around the   pupil is darker. In sectoral heterochromia (this patient’s   right eye), one section of the iris is darker than the rest.

  
 Although heterochromia is normally a benign finding   on physical examination, it may be associated with   multiple congenital syndromes and acquired diseases.

  Unilateral heterochromia that manifests as lighter   pigmentation of one iris is associated with Waardenburg   syndrome and Parry-Romberg syndrome and less commonly   with Hirschsprung disease. Waardenburg syndrome,   an autosomal dominant inherited disorder, is   characterized by a white forelock, cutaneous hypopigmentation,   wide-set eyes (telecanthus), prominence of   the nasal root, and hearing loss. Parry-Romberg syndrome   is a craniofacial disorder characterized by slow   development of hemifacial atrophy as well as seizures   and severe facial pain. Hirshsprung disease, or congenital   aganglionic megacolon, results from an absence of   ganglion cells in the submucosal (Meissner) and the   myenteric (Auerbach) plexuses in 1 or more segments   of the colon. The aganglionic segment is limited to the   rectosigmoid colon in 75% of patients and the entire   colon in 10% of cases. In short-segment Hirshsprung disease,   only the region of the internal sphincter is affected.

Unilateral heterochromia that manifests as darker   pigmentation of the iris is associated with ocular or oculodermal   melanosis and Sturge-Weber syndrome. Ocular   melanosis is caused by an increase of melanocytes in   the iris and choroid. When the skin supplied by the ophthalmic   and maxillary divisions of the trigeminal nerve   is also involved, the condition is called oculodermal   melanosis, or nevus of Ota. Ocular melanosis may cause   glaucoma and is associated with a higher than normal   risk of malignant transformation to melanoma. Sturge-   Weber syndrome is a phakomatosis that is characterized   by a port-wine stain of the face (generally in the ophthalmic   division of the trigeminal nerve), glaucoma,   seizures, mental retardation, intracranial calcifications   that are typically paired (often referred to as trolley   tracks), and ipsilateral leptomeningeal angiomatosis.

Heterochromia as a manifestation of Horner syndrome   is a result of interrupted sympathetic innervation   of the eye.

Patients with Horner syndrome have mild to   moderate ptosis, slight elevation of the lower lid, miosis,   and dilation lag with removal of light stimuli-regardless   of the level of sympathetic interruption. The affected iris   is generally lighter because of the role sympathetics play   in melanin production in the superficial stroma. In children   who have Horner syndrome with heterochromia,   especially those with increasing iris hypopigmentation,   imaging must be performed to rule out neuroblastoma.

Acquired heterochromia may be caused by injury   (eg, a retained iron-containing foreign body can cause   siderosis and darkening of the iris), inflammation   (Fuchs heterochromic iridocyclitis),

 medications (certain   glaucoma medications, specifically prostaglandin   analogues),


 This boy’s parents were most concerned about   Horner syndrome, of all the associated conditions, because   they thought his iris may have changed color.   The parents were reassured that the child’s heterochromia   was a benign variation in iris color that was   probably inherited. On examination of the father’s eyes,   the central aspect of his iris appeared darker than the   periphery, consistent with central heterochromia.

 Swann PG. Heterochromia signs & symptoms. 

 Renard D, Jeanjean L, Labauge P. Heterochromia iridis in congenital Horner’s  syndrome. 

 Beynat J, Soichot P, Bidot S, et al. Iris heterochromia in acquired Horner’s  syndrome [in French]. 

 Jones NP. Fuchs’ Heterochromic uveitis: a reappraisal of the clinical spectrum.  

Camras CB. Comparison of latanoprost and timolol in patients with ocular  hypertension and glaucoma: a six-month masked, multicenter trial in the United  States. The United States Latanoprost Study Group. 

 Skalicky SE, Giblin M, Conway RM. Diffuse iris melanoma: report of a case  with review of the literature. Clin Ophthalmol. 2007;1:339-342.  8. Demirci H, Shields CL, Shields JA, et al. Diffuse iris melanoma: a report of  25 cases. 

Articles

A 6-month-old boy with different colored eyes since birth. The parents are concerned that the eye anomaly may be associated with an underlying condition after reading about eye disorders online.

V. Kockler, MD

Articles

Young Boy With Different Colored Eyes