Overcoming the Odds of Familial Monosomy 7

Imagine winning the Powerball jackpot — more than once.

To Danni and Brent Treu, that scenario may actually sound plausible. After all, their three children have a condition so rare that doctors have compared its odds of occurrence to that of winning the lottery.

Several years ago, the couple learned their 5-year-old son, Brady, had a bone marrow disorder called monosomy 7 syndrome. The condition occurs when a child’s bone marrow cells have only one copy of chromosome 7, instead of the usual two.

“The doctor told us, ‘There’s one of two things that will happen. It’s either going to turn into leukemia, which will be really hard to get rid of with monosomy 7, or Brady’s going to go into full-blown marrow failure and quit making blood,’” Danni recalls. “The only cure was a bone marrow transplant.”

Sobering surprises

Brady’s younger siblings underwent tests to see which one might be a bone marrow donor.

The answer was “neither.”

All three children had both monosomy 7 and myelodysplastic syndrome (MDS). In MDS, bone marrow cells don’t produce the normal blood cells that transport oxygen, clot the blood or fight infections. Children with familial monosomy 7 syndrome and MDS are also apt to develop an aggressive form of acute myeloid leukemia (AML).

“It’s really rare for one kid to have MDS, or for one kid to have monosomy 7,” Danni says, “but when you hit all three of them in the same family, basically it’s unheard of.”

It’s a lottery no one would choose to enter. But St. Jude Children’s Research Hospital has helped this family overcome the odds.

Now, new research may help other children born with the condition.

Two genes, many possibilities

Jeffery Klco, MD, PhD, of St. Jude Pathology and his colleagues recently made important discoveries about the disorders that affect the Treu family. The findings may help some patients avoid the risk, stress and expense of bone marrow transplantation.

For decades, researchers searched for the origin of familial monosomy 7 syndrome. Then Klco and his team, as well as investigators in Europe, discovered the condition is caused by germline mutations in the genes SAMD9 or SAMD9L. Usually inherited, germline mutations occur in the DNA of every cell.

Scientists from St. Jude and the University of California, San Francisco, led by Kevin Shannon, MD, studied 16 patients from five families with SAMD9 or SAMD9L mutations. Some of the children had monosomy 7, a few developed MDS and even a couple got AML. But the scientists were astounded that some of the children regained normal bone marrow function without therapy.

“Historically, these kids usually get bone marrow transplants,” Klco says. “Now we know that in children with these mutations, sometimes the monosomy 7 cells go away.”

As a result, scientists are developing guidelines to pinpoint which children require transplants and which can avoid them.

Three success stories

The Treu children were not a part of Klco’s recent study, but their experience mirrored that of the participants. To head off AML development, Brady and his younger sister, Charlee, underwent bone marrow transplants from unrelated donors. But the symptoms of their little brother, Bentley, simply melted away like snow in the sunshine.

SAMD9 and SAMD9L have now been identified as cancer predisposition genes, so St. Jude includes them in genetic screenings for patients who have bone marrow abnormalities or leukemia. Klco’s team also identified other mutations that, when paired with SAMD9 or SAMD9L alterations, cause AML.

He predicts many more exciting advancements in the future, as the hospital opens a new clinic for patients with bone marrow failure disorders such as MDS.

The search continues

To answer even more questions, Klco is dedicated to working with researchers worldwide, including St. Jude colleagues Jason Schwartz, MD, PhD, and Marcin Wlodarski, MD, PhD, of Hematology.

“Now we’re trying to figure out how the mutations ultimately lead to monosomy 7 and MDS,” Klco says. “What are the triggers? Why do some children have spontaneous recoveries? There’s still a lot to do.”

Danni says she’s thankful Klco and other researchers continue their quest.

 “It’s so important to do research on rare disorders like this one,” she says. “If you don’t do research, how can you ever detect the disease or develop better treatment plans for it?”