Researchers Identify Previously Unknown Condition That Affects Children, Find Possible Treatment

An international team of researchers has identified the previously unknown genetic condition that affects children and even found a possible way to prevent it.

Doctors have been baffled by a condition that occurs in children. It affects the prenatal development of organs including the brain, hands, eyes, kidneys and heart, the University of California (UC) San Diego noted in a news release. Kids afflicted by the condition tend to "suffer from lifelong disabilities."

"We have been perplexed by children with this condition for many years," Joseph G. Gleeson, MD of UC San Diego and Rady Children's Institute for Genomic Medicine, senior author of the study that was published in The New England Journal of Medicine, said.

Zaki Syndrome

Through whole-genome sequencing of samples obtained from the children, their parents or both, the researchers identified mutations in the WLS gene, which regulates the signaling levels for Wnt, a hormone-like protein that's involved in embryonic development, UC San Diego noted.

"Patients had multiorgan defects, including microcephaly and facial dysmorphism as well as foot syndactyly, renal agenesis, alopecia, iris coloboma, and heart defects," the researchers wrote. "The mutations affected WLS protein stability and Wnt signaling."

"We had observed children around the world with DNA mutations in the Wnt-less (WLS) gene, but did not recognize that they all had the same disease until doctors compared clinical notes," Gleeson said. "We realized we were dealing with a new syndrome that can be recognized by clinicians, and potentially prevented."

The researchers dubbed the condition Zaki Syndrome, after study co-author Maha S. Zaki, MD, PhD of the National Research Center in Cairo, Egypt, who was actually the one who first spotted it, UC San Diego noted.

Potentially Preventable Disorder

Apart from identifying the condition, the researchers also tested candidate treatments for it. Using mouse models with the pathogenic variant "knocked in," the researchers administered the Wnt antagonist to pregnant animals and looked at their offspring.

They found that using the drug known as CHIR99021 boosted the Wnt signals and "restored development." It even led the mouse embryos to grow the missing body parts and continue the normal growth of organs, the university noted.

"Administration of a pharmacologic Wnt agonist partially restored embryonic development," the researchers wrote. "Results from mouse models suggest that what we have named Zaki syndrome is a potentially preventable disorder."

The idea is by administering the drug during the mother's pregnancy, perhaps it would be possible to prevent the gene mutation, UC San Diego noted.

"The results were very surprising because it was assumed that structural birth defects like Zaki syndrome could not be prevented with a drug," study first author Guoliang Chai, PhD, who is now affiliated with the Capital Medical University in Beijing, China, said in the university news release. "We can see this drug, or drugs like it, eventually being used to prevent birth defects, if the babies can be diagnosed early enough."