May I See His Toes?
When the young child and his family first came to Wills Eye, the lengthy search for definitive answers weighed heavily on them. Born with incomplete hearing loss, the child was referred from specialist to specialist over several years, including an ophthalmologist who noted pigment changes in the child’s retinas. Over the next several years, those pigment changes worsened and began to affect the child’s vision. Answers were elusive.
The Pediatric Ophthalmology and Ocular Genetics Service led by Dr. Alex Levin grapples with the rarest of the rare mysteries in ophthalmology. Many of the diagnoses by Dr. Levin and his team affect 10 families or less in the entire world. In medicine, they call these diseases “zebras,” and physicians are taught to discount the possibility of seeing one due to their extreme rarity. However, in the halls of Dr. Levin’s clinic, “zebras” walk every day.
The family and the young patient prepared for yet another exam. Dr. Levin looked at the youth’s retinas. He saw clumps of pigment. Brownish-black. Other physicians believed that the patient may have a genetic condition called Usher Syndrome; however, Dr. Levin, having seen Usher Syndrome many times, knew that the clumps of pigment didn’t look right. In Usher Syndrome, the pigment takes on a honeycomb-like shape. In this patient, the pigment was more round, and cysts were present.
Dr. Levin stepped back and contemplated the rest of the patient’s physical condition. The youth had small teeth with no enamel on them. There was retinal degeneration with hearing loss. Then, Dr. Levin asked a question that seemed very odd for an eye doctor to ask. The parents were taken aback.
“May I see his toes?”
His suspicion was confirmed. The child had characteristic, horizontal lines in his toenails called Beau’s lines. Dr. Levin knew he had the answer the family was so desperate to learn. “Heimler Syndrome,” he said. Heimler Syndrome is a genetic disorder afecting only a handful of patients globally. But no one knew what caused Heimler Syndrome. Not yet. And that wasn’t good enough.
Jenina Capasso, MS, Licensed Certified Genetic Counselor, got to work. She submitted DNA samples for exome testing, where the patient’s DNA is compared against databases of DNA in the hope of Finding the genetic mutation responsible for the patient’s disease. Two labs could not find the mutation. The third, however, found it in a completely unexpected place: a gene that is associated with a number of other diseases that don’t affect the eye.
The gene is called PEX6 and affects cellular structures called peroxizomes. These tiny structures are like bags of enzymes inside of cells that help metabolism. It turns out that these peroxizomes are important in the specialized rod and cone cells found in the retina that turn light into neurological impulses. It was disease in these peroxizomes that was causing the eye disease portion of this young patient’s condition. A new mechanism of disease had been found.
Although there is no treatment today for Heimler Syndrome, knowing the precise genetic mutation and disease process now gives scientists a place to start looking for a treatment or cure. Most importantly, this family now understands what is happening in their child’s body. The uncertainty is gone. It also allows them to connect with the other families in the world that have been touched by this condition. That support and understanding is invaluable.