By Greg Raver-Lampman
A determined geneticist uncovers extremely rare syndrome.
The first time Dr. Virginia Proud met Ryan Poteet, the five-year-old sat in an exam room full of specialists perplexed by the mystery before them: a small boy with symptoms so unusual they couldn’t put their fingers on a diagnosis.
That first day, Dr. Proud, a medical geneticist, got a sense of Ryan’s intelligence and wit, and his bewildering array of skeletal and physical anomalies. Over five years of Ryan’s life, she learned, none of the specialists could definitely say what caused Ryan’s malformed bones and organs, including kidneys riddled with cysts.
“I’m going to get to the bottom of this,” Dr. Proud quietly assured Ryan’s mom, Diane Graham of Chesapeake. Diane had been waiting for a definitive diagnosis since the day of Ryan’s birth in 1992 and didn’t know what to make of this vow from an unassuming woman who spoke in quiet, comforting tones.
In the years since, Diane’s view of Dr. Proud has changed radically.
“She’s a pit bull in disguise,” Diane said of the determined medical detective who did indeed make good on her promise.
Most lay people, schooled by high-tech medical dramas and crime shows like CSI, assume that a medical geneticist’s role amounts to research or possibly using sophisticated DNA sequencing to magically provide a diagnosis.
Despite enormous advances in genetic testing over the last ten years, there’s still no screen that can identify a genetic condition unless doctors have a good idea in advance what they’re looking for. With prenatal amniocentesis, for instance, geneticists can scan only for specific genetic abnormalities that cause conditions such as Down syndrome.
“You essentially have to know what you’re looking for,” said Dr. Proud.
To find the causes of rare syndromes like Ryan’s requires serious medical detective work. For Dr. Proud, who joined Ryan’s treatment team in 1997, finding the correct diagnosis is critical, she says, because it will usually lead to better clinical treatment.
In Ryan’s case, puzzle pieces were scattered through hundreds of pages of medical documents, X-rays, MRIs and ultrasounds generated over five years.
Virtually every bone in Ryan’s body, from his knuckles to his toes, was misshapen.
One specialist speculated that Ryan suffered from a rare genetic disorder called Melnick Needles syndrome, which alters production of a protein called “filamin A” that acts as both glue and scaffolding for bones and other tissues. That diagnosis seemed reasonable when Ryan was an infant, but as years passed it became clear that Ryan’s condition could not be explained by Melnick Needles syndrome.
“Sometimes you just simply have to start over and take a new look, so that’s what we did with Ryan,” Dr. Proud said.
Dr. Proud plowed through notes cataloguing Ryan’s skeletal anomalies and one term jumped out at her: “serpentine fibula.” One radiologist had noted in Ryan’s records the strange shape of his leg bones. Dr. Proud pulled up the film and could see exactly what the note meant – the fibula, a long, slender leg bone, descends beside the sturdier tibia from the knee to the foot. Ryan’s had a gentle, almost elegant curve.
“I’ve seen a serpentine fibula described only a few times in the medical literature,” Dr. Proud said.
Also, the ultrasound of Ryan’s kidneys showed that they were riddled with cysts, a finding that didn’t fit the earlier diagnosis and provided another key to solving the mystery: Polycystic kidneys, Dr. Proud knew, occur rarely in genetic disorders.
Armed with these two findings, Dr. Proud came up with a strategy – narrow down the possibilities by searching for genetic syndromes that cause both serpentine fibula and polycystic kidneys. Dr. Proud plugged the criteria into a database of genetic disorders catalogued by the anomalies they cause. Only one genetic disorder produced both symptoms, Hajdu-Cheney syndrome, a genetic condition so rare that only 70 cases have been reported worldwide since the 1950s, when it was first discovered. Dr. Proud combed through the list of skeletal and physical deformities caused by the rare condition.
They fit Ryan like a glove.
Dr. Proud discovered a journal article on a child with Hajdu-Cheney that included a picture. The resemblance to Ryan was striking.
Soon after Dr. Proud delivered the news to Ryan’s mother, Diane saw an article on a little girl with Hadju-Cheney syndrome and a picture of the girl. Her resemblance to Ryan was unmistakable. Diane e-mailed the mother of the girl in the article and they eventually met.
“It was so nice to talk to somebody who understood what we were going through,” Diane said. She has made it a crusade to find other Hadju-Cheney patients, and has come across 12, including one who is a college student.
While Dr. Proud’s diagnosis of Ryan’s condition earned her a featured role in a recent episode of the Discovery Channel’s Mystery Diagnosis, filmed at CHKD in 2008, she considers making the diagnosis the beginning, not the end. Today, Dr. Proud remains on the hunt to identify the precise problem in genetic coding that causes Hadju-Cheney, a step toward finding a possible cure.
In the years since his diagnosis, Ryan continues to be seen by many specialists, including CHKD physicians, for scores of medical and skeletal complications related to Hadju-Cheney, but he’s never allowed that to affect his spirit. Now a junior in high school, Ryan is witty, intelligent and popular. His favorite hobbies are break dancing and golfing, which he does in charity tournaments.
His success in navigating a world in which his limitations are many can be summed up in his personal motto.
“I may be small,” Ryan says, “but my heart is large.”
Dr. Proud practices with Children’s Specialty Group PLLC at CHKD.
This story was featured in the fourth quarter 2009 issue of KidStuff, a publication of Children's Hospital of The King's Daughters.