An eye exam for a 5-year-old boy turned up something striking: sharply outlined patches of ice-gray color set within otherwise normally pigmented irises in both eyes. The rest of his eye exam was normal.
The finding took on added meaning because of the boy's past. Five days after he was born, he developed an intestinal blockage. He was later diagnosed with Hirschsprung disease, a rare birth defect in which nerve cells are missing from part of the intestine.
The case, titled Bilateral Sectoral Iris Heterochromia and Hirschsprung Disease in a 5-Year-Old Child, was published online July 23 in JAMA Ophthalmology. It highlights a rarely reported pairing that links two parts of the body that seem to have nothing in common.
Patches of Color in Both Eyes
Heterochromia means differences in eye color. It can involve two different-colored eyes, a ring of color around the pupil, or, as in this boy, sectoral heterochromia, in which a wedge or patch of the iris differs from the rest.
The National Library of Medicine's MedlinePlus notes that heterochromia is uncommon in people and can be inherited, linked to a disease or syndrome, or caused by injury. It advises a thorough eye exam when a baby has two different-colored eyes or when a person notices a new change in the color of one eye. Some related conditions, such as pigmentary glaucoma, can only be detected through that kind of detailed exam.
According to the published report, this boy's patches were bilateral, meaning they appeared in both eyes, with a distinct ice-gray tint.
A Blocked Bowel in the First Week of Life
The boy's intestinal problems began almost immediately. At 5 days old, he developed an obstruction and underwent an exploratory abdominal operation and a colostomy, the report says. A rectal biopsy later showed missing ganglion cells, the nerve cells that control the bowel, along with enlarged nerve fibers, confirming Hirschsprung disease.
The condition affects about 1 in 5,000 newborns, according to the National Institute of Diabetes and Digestive and Kidney Diseases. Without those nerve cells, the affected stretch of intestine cannot move stool forward, so it becomes blocked. Some infants show signs of obstruction shortly after birth, while older infants and children more often have chronic constipation and a swollen abdomen. Boys are affected more often than girls.
Doctors confirm the diagnosis with tests such as imaging, anorectal manometry, and rectal biopsy. The usual treatment is a pull-through operation, sometimes preceded by ostomy surgery, and most children feel better afterward. Certain genes raise a child's chance of developing the condition.
The authors reported that a detailed systemic examination found no other relevant abnormalities.
The Embryonic Link Between Eye Color and Gut Nerves
The connection between an iris and an intestine traces back to early development. Researchers have long pointed to the neural crest, a population of embryonic cells that migrate throughout the body and give rise to many tissues, including nerve cells in the gut and pigment-related cells.
Hirschsprung disease occurs when neural crest-derived cells fail to fully colonize the lower bowel. Because parts of the iris also have ties to the neural crest, investigators have proposed that a single developmental disturbance could affect both areas.
The idea is not new. A 1983 report described bicolored irises in both eyes of a patient with Hirschsprung disease. A 1992 report from Toronto's Hospital for Sick Children described a 6-month-old girl with biopsy-proven Hirschsprung disease and sector heterochromia. When her eyes were examined under the microscope, the affected areas showed thinner iris tissue, less pigment, and fewer pigment-producing cells. A 1998 study from Hong Kong later compared bilateral iris sector heterochromia in children with and without Hirschsprung disease.
Still, the link remains an association supported by case reports and small studies, not a proven cause-and-effect relationship. Sectoral heterochromia is usually harmless, and the pairing with Hirschsprung disease is rarely reported.
A Syndrome Doctors Look For
Eye color differences and Hirschsprung disease can also appear together as part of Waardenburg syndrome type 4, also called Waardenburg-Shah syndrome. This rare inherited condition can also involve hearing loss and pigment changes in the skin and hair. In one report from China, a 5-month-old boy with the syndrome had gray-blue irises in both eyes, Hirschsprung disease, and hearing loss tied to a change in the SOX10 gene. That overlap is one reason clinicians carefully examine children with unusual iris pigmentation for other signs.
In this boy's case, the report describes no additional relevant systemic findings, which makes the combination of isolated sectoral heterochromia and Hirschsprung disease especially notable.
For parents, the case does not mean that a child with patchy eye color has a hidden bowel condition. It does show how a pediatric eye exam can reveal clues that connect to a child's broader medical history. Families who notice a new change in a child's eye color, or signs such as chronic constipation or a swollen belly, should talk with their child's pediatrician.
Key Questions Answered
What is sectoral iris heterochromia?
It is a patch or wedge of the iris that has a different color from the rest of the iris. In this case, both eyes had ice-gray patches.
What is Hirschsprung disease?
It is a birth defect in which nerve cells are missing from part of the large intestine, so stool cannot move normally and the bowel becomes blocked.
Why would eye color be linked to a bowel disorder?
Gut nerve cells and parts of the iris both have ties to the neural crest, a group of embryonic cells. Researchers suspect a shared developmental disruption may explain some cases.
Does patchy eye color mean a child has Hirschsprung disease?
No. Sectoral heterochromia is usually harmless, and its pairing with Hirschsprung disease is rarely reported.
When should parents seek medical advice?
When they notice a new change in a child's eye color, two different-colored eyes in an infant, or persistent constipation and abdominal swelling.
