By James Hanlon
Leader Staff Writer
Stan Gibson, an Oxford resident, has had a strange set of conditions throughout his life including childhood glaucoma (a condition that causes blindness), skin rashes and tendons that tear easily. He inherited these conditions from his father’s side. His grandfather and some of his father’s siblings had similar symptoms and died young.
Since Stan and his relatives developed symptoms in early childhood, he thought his own seven children were safe until his youngest, Rachel, started holding her eyes and head, complaining of pain and light sensitivity at the age of three.
Rachel had several unsuccessful surgeries that left her eyes further damaged until a surgeon at University of Michigan’s Kellogg Eye Center was able to reconstruct her eyes and save her vision.
Then their son Adam, who was 13 at the time, suddenly said he couldn’t see anything after a family outing. “We thought Adam was in the clear since he was older than six; we had stopped screening our children for the glaucoma,” said Adam’s mother, Eryn Gibson.
He had emergency surgery at Kellogg, where most of his vision was saved, except a small amount of peripheral vision loss. “If it wasn’t for Kellogg Eye Center, both of my kids would be blind,” Eryn said.
That was eight years ago, shortly after the family moved to Lake Orion from California for Stan’s engineering career. But they were always drawn to Oxford, where they found their “forever home” in 2017.
“Maybe the most important thing to know about what it’s like to live with this disease is how incredibly kind our friends and neighbors in Oxford have been,” Stan said. “People we barely know have gone out of their way to make us feel loved and supported. We are constantly meeting with patient, thoughtful people. That truly makes all the difference. It allows our family to move forward with a lot of hope.”
Another set of symptoms they share comes from calcification of soft tissues in the body, causing excruciating pain and can lead to early death. “We deal with the vision loss by using adaptive technology. The calcification is harder as the constant pain causes sleepless nights and emotional exhaustion,” they said.
As Stan’s sight has worsened, he has shifted to contract work from home where he can use aids for the visually impaired. Fortunately, they have been able to take advantage of the flexibility of educating their kids at home with the help of Oxford Virtual Academy. During the last year, Eryn took on a new role directing a hybrid partnership with OVA called Oxford Hybrid Secondary School. “Working with students in our community gives us a chance to give back a bit,” Eryn said.
According to the U-M Health Blog, the family history and strange pattern of emerging symptoms led the Kellogg Eye Center glaucoma genetics team to search for the common genetic cause. Dr. Lev Prasov, a genetic eye disease specialist at Kellogg, led the research in collaboration with the National Eye Institute of the National Institutes of Health (NIH).
The team meticulously interviewed family members to draw a pedigree. The Gibsons even took a trip to Utah to get blood and saliva samples from family members. The researchers determined that this was an autosomal dominant condition, meaning there is a 50 percent risk of it being passed down.
Next, the team sequenced the protein coding DNA from affected and unaffected family members, a process called whole exome sequencing. Looking through the data, they found a misspelling in the DDX58 gene that had never been observed before. This gene encodes for a protein involved in the immune system. Stan, Rachel and Adam all shared this mutant variant.
“With the genetic testing, we were able to conclude this disease was Singleton-Merten syndrome type II – an extremely rare, autosomal, dominant condition with only three families documented in literature,” Dr. Prasov explained.
Another family, far away on the equator in Belém, Brazil, had a similar set of symptoms and the same genetic variant in DDX58. By comparing notes among all of the identified families, Prasov led an international team of researchers from U-M, the NIH, Brazil, and Harvard, to make the first complete molecular and histological assessment of the eye and skin findings in Singleton-Merten syndrome type II. They showed how the mutation triggers inflammation throughout the body. The findings were recently published in the Journal of Medical Genetics.
There’s still a lot left to learn about the condition, especially how to better treat or prevent it, but the progress is reassuring. “Because of the communication between these doctors, more of this condition is now better understood,” said Eryn. “Their curiosity led to answers, but also helped us feel like we were finally being heard and cared about. Finally, after generations of unanswered questions and enormous health challenges someone took this seriously and had access to the resources to find answers about this condition.”
“This is something I want to explore more,” Prasov said. “Rachel and Adam don’t have many of the system effects of this disease, but they could develop them in the future. Understanding all the factors that may provoke more severe illness may help us be able to prevent those developments from occurring.”
Stan takes medication that helps calm the immune system and stop the disease from getting out of control. He says the medication has helped his skin discoloration resolve.
“I’m so grateful to know what this condition is,” Stan said. “Knowing how to treat it would be a miracle, but you have to start somewhere. This research will benefit my own children but also their children when they start families of their own. They know what to look out for.”