CDKL5 Deficiency Disorder: Avery's Story

Avery was Kristin and Brian’s third child, so they had a good sense of normal infant behavior and development. In their first few weeks at home with Avery, they noticed a pattern of unusual movements. She would stiffen, turn red in the face and throw her arms out. When Kristin called her pediatrician, she was told not to worry. It was three weeks after Avery’s birth, when she also started to hold her breath until her lips turned blue, that Kristin became worried enough to bring her to the local emergency room.

Treatment for seizures at CHOP

Kristin chose Grand View Health in Bucks County, which, by a fortunate chance, is home to CHOP’s Newborn and Pediatric Care center. A CHOP doctor immediately recognized Avery’s movements as seizures. The baby was quickly transferred to CHOP’s Harriet and Ronald Lassin Newborn/Infant Intensive Care Unit (N/IICU), where, over the next week, her seizures were stabilized with medication.

Avery had a short respite at home, but a few days later the seizures resumed. She was re-admitted to CHOP under the care of Robert Clancy, MD, a pediatric neurologist who specializes in treating children with epilepsy. Over the next three weeks, Avery’s medical team worked to find a combination of medicines that would bring her seizures under control. Genetic testing was also done in an effort to find the cause of Avery’s problems.

The challenge of managing Avery’s seizures over those weeks was the family’s first taste of what would be a long struggle. Avery’s condition has shown a pattern of responding to seizure medications only for a limited time. When one treatment stops working, a new medication must be tried in slowly increasing doses. If the new treatment doesn’t work well enough, the doses have to be gradually decreased before a different medication can be tried. “Even now,” says Kristin, “one of the most frustrating things is how long it can take to switch a medication.”

Diagnosis with CDKL5 deficiency disorder

Avery was able to go home again, where her older sisters doted on her. A few weeks later, when Avery was 4 months old, Dr. Clancy called with a diagnosis. The genetic testing had identified a mutation in the CDKL5 gene, which is responsible for creating a protein necessary for normal brain development and function.

Avery was one of the youngest patients to be diagnosed with CDKL5 deficiency disorder, not because the condition doesn’t occur in newborns, but because it is relatively rare and testing for it was uncommon at the time.

Even with the diagnosis, Avery’s prospects weren’t clear. While there are some similarities among children with CDKL5 deficiency disorder, the presentation varies widely. Each patient has a mutation at a specific spot in the gene. Avery’s point mutation was unique to her; no other case had been documented. “All Dr. Clancy could tell us,” remembers Kristin, “was that it was significant and that it was causing her seizures. He couldn’t say what it would mean for her.”

Therapy and medication

The diagnosis did provide a bit of certainty. It confirmed that the treatment approach was appropriate. Avery would continue to need anti-seizure medication, and, if her case followed the progression of similar cases, each medication would eventually stop working and need to be replaced by another. She would also benefit from early intervention — Avery started physical, occupational, speech and vision therapy.

With the diagnosis, Kristin was able to find out more about Avery’s condition and connect with other parents whose children were affected. Much of what she learned was alarming: most children with CDKL5 deficiency disorder never walk, never talk and remain completely dependent on others. Those forecasts have turned out be true for Avery, but they didn’t tell the story of the lovable, interactive child she would become.

A broad team of specialists

At four months, Avery was being treated by Dr. Clancy in the Division of Neurology and receiving therapy at home for movement, feeding and other skills. Her circle of care was also expanding to other specialties.

CDKL5 deficiency disorder often involves vision problems. Avery’s eyes function properly, but her brain has difficulty making sense of visual information. She has received vision therapy from an early age and has regular appointments with an ophthalmologist at CHOP.

She has also received support and treatment from CHOP nutrition and gastroenterology experts. In coordination with her epilepsy team, Avery was put on a ketogenic diet, which has helped to control her seizures. After a prolonged seizure at the age of 4, she lost some of her ability to swallow and was put on a feeding tube. Avery has recovered her swallowing ability, but she still has a G-tube for supplemental nutrition and medication.

Because she sees so many specialists and receives such frequent treatment, Avery’s care is coordinated through the CHOP Compass Care Program, a service that helps families manage appointments for children with complex conditions. 

Putting It All Together

In the fall of 2019, the multidisciplinary CDKL5 clinic was designated as a Center of Excellence, one of only eight in the U.S. Avery was among the first patients to benefit from the clinic, thanks to her long relationship with CHOP’s CDKL5 experts and her family’s involvement with the larger CDKL5 community (Kristin serves on the board of the International Foundation for CDKL5 Research, the organization that designates the Centers of Excellence).

In her visit to the clinic, Avery was seen by Eric Marsh, MD, PhD, a neurologist with a specialty in developmental epilepsy, as well as experts in physical medicine, gastroenterology, genetics, physical therapy and occupational therapy. These specialists also have developed an expertise in CDKL5 deficiency disorder and have treated other children with the condition, so they are knowledgeable about the unique needs of these patients. Avery’s visit was arranged so that each expert came to her room, which made the multiple appointments much more convenient. The specialists consolidated their recommendations to share with Avery’s regular care providers.

The clinic is also involved in research and is a resource for information about clinical trials. Avery has participated in one clinical trial, which is still ongoing.

“I’m pleased that we have a Center of Excellence at CHOP,” says Kristin. “It’s a way to make CHOP’s CDKL5 expertise easily accessible to families, whether they live nearby or have to travel here. They’ll offer guidance to the children’s regular specialists and the people providing therapies. And they’ll be coordinating research into the condition and treatments.

“I can’t overstate how important it is to move forward with research for this disorder. My husband and I say all the time how lucky we are to have CHOP, with this amazing level of care and expertise. I just don’t know how we would have managed without them.”

An adorable kid

At 6, Avery is fully involved with her family’s active life. “When we go for family bike rides, Avery is with us,” says Kristin. “She’s with us when we go for family walks and when we go skiing.” Avery uses a sit-ski tethered to her father. She loves being outdoors and being active with her family. “She loves playing with her older sisters,” says Kristin. “They sing to her and read to her. She’s vocal; she coos back at them. They like to run with her and swing with her on the swing set. She’s super adorable — a happy, pleasant, easy-going kid.”