Rare Disease Turning Little Girl to Bone

F O R T   L E E, N.J., Dec. 10 -- Sophia Forshtay wakes up on a Sunday morning, a 4-year-old singing happily to herself in bed. Her tiny melody floats through the house, mixing with the aroma of breakfast coffee.

There’s a sad note: Lying on her back, she can’t turn her head.She can’t lift her arms.

Sophia’s body is slowly, inexorably turning to bone.

She is one of about 2,500 people around the world withfibrodysplasia ossificans progressiva, or FOP.

“It’s like a terrorist setting off a bomb inside thesechildren, a supreme sabotage. But we can’t predict where and whenit’ll strike,” says Dr. Fred Kaplan, an orthopedist who hasdevoted his life to solving the mysterious genetic disorder.

Like detectives in a medical thriller, he and other scientistsare racing to identify the strange force in Sophia’s limbs. Andthey’re finding clues in the unlikeliest places—a shark, a fruitfly, a tadpole.

Daily Courage

Oblivious to the genetic time bomb ticking in her, the littlegirl skips through the kitchen hugging her stuffed rabbit. Sheloses her balance and falls backwards, landing in her sister’sarms. The impish grin disappears. Fear shines in her eyes. Sherights herself, puts on a smile—and runs off.

“It takes a lot of courage to live like this,” says ConstanceGreen, Sophia’s mother. “It’s got to be terrifying not to be able to stop yourself when you’re about to fall.”

In vain, Sophia struggles to put a peanut in her mouth, pushingher arm to its limit. Her hand gets stuck in a coat sleeve, but shewiggles out, exclaiming, “Hey, I found my fingers!”

And she reassures a concerned friend holding on to her as shemounts the stairs, “Don’t be scared! I’m here.”

FOP Riddle

In a Philadelphia laboratory, Kaplan and molecular biologistEileen Shore, the lab’s director, are working with a dozenresearchers to solve the riddle that began at conception for Sophiaand the other “FOPers,” as they’ve dubbed themselves.

A spontaneously mutant gene enters the fetus, carried either bysperm or egg. Sometime during childhood, this unknown gene triggerspainful swellings in muscles and tissue that then turn intorenegade bone cells. Eventually, the body is imprisoned in a“second skeleton”—quite literally, a life sentence. A joint can lock overnight, never to move again.

Exactly where in the vast library of human genes is the errantcode that spurs the wild bone growths? How can this master switchbe turned off?

“I wanted to tackle something big. I wanted a mountain toclimb,” says Kaplan, who is leading the work at the University ofPennsylvania Medical Center.

Examination

One recent afternoon, Kaplan examines Sophia, gently touching areddish bump that signals newly forming bone.

“Don’t hurt me! Stop that!” she pleads.

Minutes later, the doctor is sitting cross-legged on the floorof the hospital waiting room, a slight 47-year-old man bouncing onthe carpet, giggling and chatting.

“I need a hug!” he tells Sophia. With peals of laughter, shegrabs his hands, glee bursting from every part of her that is stillagile. He pretends to be asleep, and she nudges him: “Get UP!”

This isn’t just play. It’s how the doctor examines the girl,watching her every motion. What inroads has the bone made since helast saw her several months earlier?