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.
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.
WHAT’S YOUR DIAGNOSIS?
ANSWER: HETEROCHROMIA IRIDIS
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.1,2 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.3,4 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),5 medications (certain glaucoma medications, specifically prostaglandin analogues),6 and neoplasm (iris melanomas).7,8
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.
1. Swann PG. Heterochromia signs & symptoms. Optometry Today. January 29, 1999:30-32.
2. Ur Rehman H. Heterochromia. CMAJ. 2008;179:447-448.
3. Renard D, Jeanjean L, Labauge P. Heterochromia iridis in congenital Horner’s syndrome. Eur Neurol. 2010;63:253.
4. Beynat J, Soichot P, Bidot S, et al. Iris heterochromia in acquired Horner’s syndrome [in French]. J Fr Ophtalmol. 2007;30:e19.
5. Jones NP. Fuchs’ Heterochromic uveitis: a reappraisal of the clinical spectrum. Eye (Lond). 1991;5(pt 6):649-661.
6. 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. Ophthalmology. 1996;103: 138-147.
7. 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. Ophthalmology. 2002;109:1553-1560.