Difficult Diagnosis: Cracking the Code
How a tiny piece of missing genetic material can have a huge impact.
Fair-skinned with a slight build, Dr. Matthew Taylor smiles a wry grin as he remembers Roger Evans’ first day at the clinic. “He came to us from an endocrinologist who wanted us to do some testing,” says the doctor, who is a genetics physician at the Adult Medical Genetics Clinic at the University of Colorado Hospital. “Roger was definitely a mystery.”
“I had a perfectly normal childhood,” Roger Evans says today. “I grew up in Southern California, went to school, and graduated on time.” Evans says he was rarely sick as a child, and except for some muscle spasms in his early teens—which his father chalked up to growing pains—he says he doesn’t remember being anything but healthy.
That began to change when Evans, now 51, matriculated into his later years of high school. “I guess I was old enough to notice that I didn’t look like my younger siblings,” he says. “My eyes were different; I had a round face; my ears were short. I actually asked my parents if I was adopted at one point.” Satisfied that he was a blood member of the family once his parents showed him his birth certificate, Evans forgot all about the differences he saw in himself and got on with planning his young life. He got a few odd jobs after graduating high school, but ultimately decided to enlist in the Army in his early 20s.
Although he was still experiencing some mild muscle cramps, he passed the Army’s physical exams. “It wasn’t until I got into basic training that I noticed I wasn’t really able to keep up with the other soldiers,” Evans says. “I was short-winded and fatigued.” He made it through eight weeks of basic before, during a 10-mile marching stint, he collapsed. Evans took a medical discharge from the Army weeks later.
During the years after the Army, Evans remembers feeling sick a few times and having general weakness, but he didn’t seek medical care. At least, not until he had his first seizure in 1984 at 24 years old. “The doctors diagnosed me with low blood calcium levels,” he says. Doctors prescribed calcium tablets. For the better part of a decade, Evans lived with low calcium–induced muscle spasms and weakness but nothing that stopped him from moving to Denver for a job with Continental Airlines. Then, in 1995, the seizures returned.
Tests for epilepsy came back negative. But, once again, doctors found his blood calcium levels were dangerously low. Calcium tablets just weren’t strong enough. They prescribed Rocaltrol, and surmised that his parathyroid glands, which control calcium levels, were not functioning properly. Evans remembers asking the doctors what might be causing the glands to malfunction—but no one seemed to know.
It wasn’t until three years later, at a Christmas Eve church service, that a particularly scary seizure prompted Evans to seek a solid diagnosis. “I had recently quit my job so I had decided to go back to school,” Evans says. “I realized that I needed to get a job and get medical insurance so that I could figure out what was wrong with me. I was almost 40 years old.”
But finding a doctor—and a diagnosis—was more difficult than he’d imagined. Evans went to an endocrinologist, who eventually told him his case was too complicated for her. He tried a primary care doc, who Evans says wasn’t able to control his blood calcium levels well enough to allow him to walk. Finally, years after he’d made the decision to find out what was ailing him, Evans opened the phone book and picked the first endocrinologist on the list. He had an appointment set for February 2003 with Dr. Margaret Eagan at Rose Medical Center.
“Dr. Eagan was the first doctor I’d had that tried to help me,” Evans says. “She took an interest in me. She started from scratch.” She diagnosed Evans with rickets, a softening of the bones typically due to a vitamin D or calcium deficiency. But Dr. Eagan then sent Evans to her mentor, Dr. Michael McDermott, at the University of Colorado Denver School of Medicine. McDermott disagreed with his former colleague, and diagnosed hypoparathyroidism leading to hypocalcemia, which essentially meant Evans’ parathyroid glands weren’t functioning. But Evans already knew that. He’d been on calcium pills—and then thrice weekly, three-gram IV infusions—for years. He wanted to know why his parathyroid glands weren’t functioning.
“I remember sitting back in Dr. Eagan’s office and asking her how we go about figuring things out,” he says. The doctor looked him over again; she examined his hands and ears and nose and eyes. Evans remembers Eagan, almost under her breath, saying that it could be something called DiGeorge syndrome, a disorder she’d only once heard about in medical school. Eagan then sent Evans to Dr. Matthew Taylor.
Taylor thought there were two possible genetic issues: one, a potential genetic mutation on Evans’ calcium-sensing receptor gene (CASR). The other, which Taylor believed was a more remote possibility, was for 22q11.2 deletion syndrome, more commonly called DiGeorge syndrome, which is a defect in which certain genes get deleted from an area along the larger arm of the 22nd chromosome.
“Roger didn’t have the classic presentation of 22q deletion syndrome,” the doctor explains. “Patients with that syndrome typically have cardiac defects, immune problems, feeding problems, and developmental problems.” Evans exhibited some of the typical facial features (low ears and wide-set eyes) associated with the disorder as well as the low blood calcium levels, but 22q11.2 deletion syndrome is almost always diagnosed early in life. Evans was 43 years old.
Taylor ordered a test for the CASR mutation, which six to eight weeks later came back negative. The doctor then sent off labs for 22q11.2 deletion syndrome. Nearly 30 years after Evans’ dad told him his muscle spasms were normal for a teenage boy, Dr. Taylor told him otherwise: Evans was positively diagnosed with 22q11.2 deletion syndrome.
“It was a long, hard road, but I was thrilled to have a diagnosis,” Evans says. “I had to be my own advocate sometimes, but I had so many little angels helping me. And I did learn that just because you get an incorrect diagnosis at first doesn’t mean you should give up—sometimes you just have to work through things with your doctor.”
Although he has his diagnosis, Evans does not have a cure. Since the positive lab results, he has learned he has other characteristics associated with the syndrome: specifically, three different heart defects. And because of his need for so much calcium, his kidneys have begun to fail. But he remains optimistic—and thankful. “I’m grateful for the good doctors, like Dr. Taylor, that I ultimately found,” he says. “So many people never know what’s wrong with them. At least I know.”