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Local researchers help uncover genetic mutation that causes intellectual disability in girls

Originally posted at Lancaster Online

Local researchers at the Clinic for Special Children in Strasburg have helped to make a significant discovery of a genetic mutation that may be the cause of intellectual disabilities in some girls.

The very complex scientific discovery happened in part thanks due to a very human connection, says Karlla Brigatti, a genetic counselor at the clinic.

There’s a hearing specialist from Delaware who sees patients at the Clinic for Special Children, which specializes in diagnosing, treating, studying and discovering genetic disorders, particularly among the Plain community.

The hearing specialist has friends, who have a daughter with an intellectual disability. The couple, who live in Chadds Ford and are not Plain, had been to numerous major medical centers seeking a diagnosis of the disability, but had come up with no answers, the specialist told doctors at the clinic last spring.

Would the clinic see her?

It would and it did, though it’s not its usual type of work, Brigatti notes.

It turned out that friend-of-a-friend connection ultimately helped genetic researchers connect the dots between the girl, now 10, and a group of about 10 other girls across the country who all share the same genetic mutation and similar characteristics.

The mutation, called DDX3X, causes intellectual disabilities that can range from mild to profound, Brigatti said. Many girls with the mutation have abnormalities in the development of their brains. Some have seizures, or behavioral issues such as autism. They may have poor muscle tone, and be slow to walk and develop physically.

The discovery unfolded after the clinic’s physicians had the girl undergo the latest type of genetic screening, via a Maryland company.

The results that came back last November from the company, GeneDx, were significant in two ways.

First, the test showed a genetic mutation, possibly associated with the little girl’s disability, that had not been described in medical literature.

Also, the company searched  its database and found eight or nine other girls who all had mutations on the same gene, and who displayed similar characteristics.

“They said, ‘We think this is the real deal,’ ” Brigatti said.

Researchers from all over the world helped to author a report that DDX3X mutations are a common cause of a previously unexplained intellectual disability, in a paper published this month in the American Journal of Human Genetics.

Brigatti is listed as one of the authors, along with Dr. Kevin Strauss, the clinic’s medical director.

Researchers estimate that 1 to 3 percent of girls with undiagnosed intellectual disabilities may have the mutation, which is a significant number, Brigatti said. It may be found in as many as 1 in 5,000 girls, she said.

On Wednesday, the families of eight of those girls came from as far away as California and Oklahoma to learn more about DDX3X and from each other at an all-day workshop.

The mother of the little girl from Chadds Ford, who helped to jump-start the findings, was in the group.

“I’m mostly relieved that we finally have a name for what was different about her,” said the woman, who asked not to be identified in order to protect her daughter’s anonymity. “It’s good to have an answer but it opens up many more questions.”

Some of those questions include what causes the mutation?

It’s a spontaneous mutation that happens at conception, and is not related to activities during pregnancy, environmental factors or genes carried by the mothers and fathers of these girls. That means parents do not have to worry that future children will also have the mutation.

(However, in rare cases boys can inherit the mutation from their mothers, who do not show any symptoms.)

The biggest question for parents probably is, now that doctors know what the mutation is, is there any treatment for the girls who have it?

More research needs to be done to help identify a drug that may help the children, Brigatti said. In the meantime, the girls also can be treated with known drugs for their seizures or other aspects of the disability.

Wednesday’s family workshop helped to bring parents together, so they could learn more and also share advice on what treatments already have benefited their daughters. It also could lead to an advocacy group, Brigatti said, which could lobby for more research of the mutation.

The mom of the 10-year-old from Chadds Ford is focused on the future of her daughter, who now is learning to read. The mother wants her daughter to go as far as she can in life, and get all of the medical help, therapies and tutoring she needs to succeed.

But the mother also is focused on the here and now.

“One of my favorite pediatricians said, ‘Well she’s here and you love her,’ ” she said. “I try to keep that in my heart every day.

“She’s not suffering. She’s full of joy. Everyone who meets her is a better person because of her.”

(via Lancaster Online)