CHICORA — Most, if not all, parents think of their child as a one in a billion individual, but Elizabeth Hackwelder, born in 2013, was scientifically one-in-a-billion.

Her mother, Tara Hackwelder, said Elizabeth was born with a number of medical issues, which were found though genetic testing to be caused by a mutation of the SON gene that had only been found in four other people in the world. She suffered from neurological problems, poor growth and immune deficiencies since birth.

A genetic test confirmed that neither Tara Hackwelder or Jason Hackwelder was carrying a mutated gene that could have been passed on to Elizabeth, so she was diagnosed with the de novo mutation, a genetic alteration that is present for the first time in one family member, according to the National Cancer Institute.

The disease is now known as Zhu-Tokita-Takenouchi-Kim syndrome. It took months before Elizabeth was found to be an official case of ZTTK syndrome.

“This is new and rare, so there is no center for this, there is no one medical hospital or program or doctor you can see that specializes in treatment or care of the syndrome,” Hackwelder said. “We were actually contacted that, after further testing, they found a mutation they had that is newly discovered, and would we allow Baylor (University) to use her medical records as part of a research study they were about to publish. She was one of only five known cases in the world.”

On Aug. 6, 2021, Elizabeth died from the effects of ZTTK syndrome at the age of 8.

In the time Elizabeth’s medical records were being studied, Hackwelder met with two families in Texas that each had a child with ZTTK syndrome and formed a support group to connect with people familiar with the genetic disease.

The group started a foundation last year, the ZTTK SON-Shine Foundation, which aims to connect patients diagnosed with the disease to one another, and also advocate for research of the SON gene to potentially find a cure.

“One of the reasons we started the group, and last year started a foundation for the syndrome, is because we don't want anyone who is newly diagnosed to feel alone,” Hackwelder said. “We want them to have a safe place to learn about the syndrome; where they feel like they have a sense of community, because we all have a common thread, and that is that we all have a child who has an extremely rare syndrome that they didn't inherit from their parents.”

Erin Eun-Young Ahn, the primary researcher for the ZTTK SON-Shine Foundation, has been studying the SON protein since 2005. She said human bodies need two functional copies of the SON gene to make a protein, also called SON, that is required for the body to develop and grow normally.

Ahn said ZTTK syndrome affects so many aspects of bodily development because the loss of protein production means the same RNA is not copied across all cells.

“A lot of it is a splicing problem — that's why it affects many different body processes,” Ahn said. “Individuals with ZTTK have many other symptoms. That includes neurological problems, sleep disorder, very frequent infections, they have a hard time dealing with viral infections, common cold and other organ problems.”

Hackwelder said the syndrome affected “nearly every single body system” in Elizabeth since birth. Before she even knew about ZTTK, Hackwelder and her family looked for specialists who could help with some of the specific health problems Elizabeth was going through.

“Seizures, poor growth, immune deficiency — we had to travel to places with those specialties to find the help,” Hackwelder said. “We saw over 20 different pediatric specialties and five different children's hospital nationwide.”

Ahn said the science community has recently made significant advancements in genome sequencing, which could lead to easing the symptoms of ZTTK. Although gene research takes years because of the complexity of breaking down DNA, Ahn said researchers could find specific parts of SON malfunctions and how they affect the body.

“The best way, at this point, is to understand the mechanism of the most serious problem, and then figure out anything we can do to alleviate the symptoms,” Ahn said. “For example, which pathways are affected in the cell, which proteins are affected by the SON gene variants.”

Hackwelder said merely getting a rare disease diagnosed is difficult, first because the cause of symptoms is hard to find, but also because genetic testing is exceedingly expensive.

Some diseases remain unknown because patients cannot find the right place to get tested.

“Genetic testing is still considered experimental, so you have to provide burden of proof to the insurance company that it is worth paying for, because that testing is thousands of dollars,” Hackwelder said. “Many parents whose insurance companies will not cover it, obviously due to the extreme expense, can't afford to pay for that out-of-pocket, some people have to give up.”

The foundation raises money to fund research with hope for future treatments and a cure, and to provide programming, events and outreach to families and patients, and to educate and advocate to the world information about ZTTK syndrome

Hackwelder said she does not want other families to have to go through what her family went through in searching for answers to Elizabeth’s ailments.

“I feel the older families give younger families hope,” Hackwelder said. “Especially to newly diagnosed and parents of younger kids, where sometimes that information is very overwhelming, but at the same time, it’s nice because we can’t go into a doctor and have them tell us what it’s like to live with it as an adult.”

February is Rare Disease Month, and Feb. 28 is Rare Disease Day, and Hackwelder said the ZTTK foundation aims to promote its message throughout the month.

Elizabeth is one of four people diagnosed with ZTTK syndrome who has died from the syndrome, according to Hackwelder.

She said literature did not initially describe the syndrome as fatal, and there are some patients with ZTTK living as adults, the oldest patient being in his 40s.

Ahn also said research of ZTTK now is about finding ways to keep a patient living comfortably, because a full-fledged cure could take years.

“This information can help any family patient, clinician, patient care management in understanding their care,” Ahn said. “It is very hard to correct a DNA sequence in every single cell.”

Hackwelder is still meeting with researchers around the world who are studying genetics and genetic mutations.

In just five years, research on ZTTK syndrome has advanced significantly, Ahn and Hackwelder said, and Hackwelder said she has no intention of stopping soon.

“My knowledge of the syndrome was really a mother who was determined to learn every single thing about this rare, unknown syndrome to help her child in the best way possible,” Hackwelder said. “It’s crazy for me to think that prior to my daughter’s birth and being thrown into this world of rare, unknown disease that was complex, that I now have meetings with prominent medical departments that are well-published from around the world.”

To donate to the ZTTK SON-Shine Foundation, visit its website at www.zttksonshinefoundation.org.