Avery’s Family Finds Answers in Her Genes

A diagnosis of Coffin-Lowry syndrome and monitoring by a team of experts puts a family at ease.

Stanford Medicine Children's Health Coffin-Lowry syndrome patient Avery in pink dress

Avery Medina was barely a year old when she began to show signs that something was very wrong. After a festive Thanksgiving with her family, she suddenly became violently ill, throwing up and refusing to eat.

Her parents took her to urgent care near their home in Novato, California, where tests showed her to be severely dehydrated, with calcium levels that were sky-high. It was the start of an eight-month medical odyssey in which Avery was hospitalized three times at Lucile Packard Children’s Hospital Stanford and underwent a battery of tests and exams by a multidisciplinary team of specialists.

In August 2020, clinicians gave Avery’s parents an explanation for their little girl’s unusual problems: She was born with the genetic change for a rare condition known as Coffin-Lowry syndrome, which can impact multiple organ systems in the body.

“We were relieved. At least now we know,” said her mother, Carli Medina. “We had just been taking it day by day. We knew she had the best team possible.”

An estimated 1 in 50,000 people have Coffin-Lowry syndrome, which is caused by a genetic change that leads to dysfunction of a protein that affects many processes in the body, including growth factors, hormones, cell survival, and signal transmission in the brain, said Dena Matalon, MD, a medical geneticist at Stanford Medicine Children’s Health and one of Avery’s physicians.

Stanford Medicine Children's Health Coffin-Lowry syndrome patient Avery sitting on floor

The gene is located on the X chromosome and can cause severe symptoms in boys, who only have one X chromosome. Affected boys may suffer muscle spasticity, stimulus-induced drop attacks, cognitive disabilities, and bony abnormalities, among other difficulties. Girls have two X chromosomes, so they are less impacted, and their symptoms can vary widely, said Dr. Matalon, who had never treated a girl with the condition until she met Avery.

Avery, now 2½, was first hospitalized at Packard Children’s in December 2019, but tests provided no clear diagnosis. She was given infusions of the drug bisphosphonate to lower her calcium levels and went home for Christmas. But after the turn of the year, her condition worsened, her mother said. She continued to throw up and wouldn’t eat. She developed a fever and an infection and was hospitalized again. Because of her persistent high calcium levels, clinicians investigated the possibility of an endocrine tumor but ultimately ruled that out, much to the family’s relief.

Christy Tise, MD, PhD, a medical genetics resident at Stanford who treated Avery early on, began to suspect that a genetic change was the source of Avery’s problems. There were a few early clues, she said. Avery was very tiny at birth—only 5 pounds—and grew slowly in her first year. She is still quite small for a 2½-year-old—only about 25 pounds. She also was slow to sit up and didn’t begin to walk until she was about 18 months old, her mother said.

Stanford Medicine Children's Health Coffin-Lowry syndrome patient Avery smiling

In addition to her developmental delays, Dr. Tise noticed Avery’s unusual facial features: a broad forehead, wide-set eyes, and a tiny nose, as well as small, soft hands with short, tapered fingers.

Dr. Tise ordered two rounds of different genetic tests, but they were not conclusive. She then recommended that Avery have a more comprehensive test known as exome sequencing, which looks at all the genes that make proteins. But these tests are expensive—between $2,000 and $5,000—and weren’t covered by insurance.

Fortunately, Stanford had a connection to a nonprofit called the Little Zebra Fund, founded by two Stanford Medical Genetics graduates frustrated by financial obstacles to genetic testing. The Little Zebra Fund paid for full testing of blood samples from Avery and her parents, which helped the medical genetics team make a diagnosis of Coffin-Lowry syndrome in a matter of weeks, Dr. Tise said.

“It’s lucky that we had a way to cover the cost of the test,” Dr. Matalon said. “Otherwise we might not have figured this out.”

Dr. Tise said the results showed that Avery’s mother also has the genetic change in the Coffin-Lowry syndrome gene, though she has few symptoms other than being shorter than other female family members. “I’m only 5-foot-1. It’s always been a joke,” Carli Medina said, laughing. “My mom is 5-foot-8 and my dad is 6-foot-3.”

She said that having the genetic results and a diagnosis was enormously helpful, as she and her husband, Rieber, had planned to have another child.

“It really helps us with a future pregnancy, so we can test early,” Carli Medina said. “That was the biggest relief. We would never have found out if we hadn’t gotten that testing. We could have had a boy and we wouldn’t have known. I think that is huge.”

She said that the test results also alerted her two sisters, who underwent genetic testing as well but were not found to have the genetic change.

With a diagnosis in hand, clinicians now can carefully monitor Avery and intervene early, if necessary, Dr. Matalon said.

“We watch for all the things that could be associated with the condition,” she said. “We try to advocate for as many therapies as early as possible to maximize Avery’s developmental potential.”

Stanford Medicine Children's Health Coffin-Lowry syndrome patient Avery roaring

For instance, children with Coffin-Lowry syndrome may develop scoliosis, a curvature of the spine. Avery is now being monitored by orthopedics, which could provide her with a brace, if needed. She’s been tested for eye problems, which are a common symptom, and is being monitored by a pediatric cardiologist, as well as developmental and behavioral therapists. Carli Medina said the family has benefited from having a huge array of specialists at Stanford Medicine Children’s Health to scrutinize and monitor Avery’s condition.

“The number of doctors we saw from all the care teams has been amazing. They have all been great,” she said. “That is why we drive from Novato to take Avery there.”

Avery’s calcium levels still remain a mystery. It has never been reported before that children with the syndrome have calcium issues, so it was a bit of a surprise, said Monica Grover, MD, a pediatric endocrinologist at Stanford Medicine Children’s Health. Dr. Grover said it may be that Avery’s specific genetic change causes bone cells involved in calcium metabolism to be abnormal. She and Dr. Tise are planning to write a case report to alert other clinicians of this possibility. Avery’s calcium levels have been steadily decreasing and are now approaching normal range, she said.

“I am hopeful this is one of the diseases where we see calcium abnormalities in the first year of life and then it resolves,” Dr. Grover said.

Avery, meanwhile, behaves like a normal, willful toddler. She cheerfully runs through the house and loves to cuddle and dress her dolls in girly outfits, her mother said. She still has to be coaxed into eating, which is not unusual for children with Coffin-Lowry syndrome.

“She’s just the sweetest toddler I’ve ever met,” her mother said. “In my mind, Avery is the perfect little girl.”

Learn more at https://genetics.stanfordchildrens.org >


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