Kabuki Syndrome: Rosalie's Story

The signs were so subtle that many doctors over several months had missed them: a slight thickening of the fingertips and toe pads, one ear that was sticking out a little more than the other, almond-shaped eyes, arched eyebrows, a high palate.

Elaine Zackai, MD, a clinical geneticist at CHOP, needed to spend only a few minutes examining then 4-month-old Rosalie August, pulling out her trusty jewelers’ loupe for close inspection, before pronouncing, “We should test for Kabuki syndrome. I’m 100% sure she has it.”

Kabuki syndrome, so named because children with it tend to have facial characteristics similar to a Japanese Kabuki mask, is a rare genetic condition affecting multiple body systems. Its presentation varies greatly across the population, both in symptoms and severity. And some issues don’t present until the child gets older.

Genetic tests through the Roberts Individualized Medical Genetics Center confirmed Zackai’s opinion, built on decades of experience, and everything fell into place. The elusive diagnosis helped explain not only the visible signs, but the many medical difficulties Rosalie was experiencing.

“As Dr. Zackai was leaving she told me, ‘Don’t Google it,’ but I did,” says Rosalie’s mother, Dara. “At first I thought, ‘No way.’”

Because Rosalie’s father is half Japanese, Dara had another explanation for Rosalie’s eyes. But the more Dara read about the full range of symptoms, the more she believed.

Birth hospital unaware

Rosie was born at a local hospital and spent a month in the newborn intensive care until she came home on a nasogastric tube because she had trouble getting enough nutrition by mouth. When Dara pointed out other troublesome features to the doctors there, like her fingertip pads and misshaped ear, “they made me think I was crazy,” she says “But Rosie is my second child. I knew something was off.”

Rosalie was in and out of the hospital a few times over the next three months before she was admitted to CHOP with low blood sugar. Dara had to keep startling Rosalie to keep her awake when she tried to give her a bottle. “She’d take a couple sucks then dose off,” Dara says. “I knew that wasn’t normal.”

Once at CHOP, the diagnoses kept coming, and most — in retrospect — were related to Kabuki syndrome.

Hyperinsulinism and heart defects

Rosalie’s low blood sugar was the result of congenital hyperinsulinism (HI), which is common in children with Kabuki syndrome. Since she didn’t respond to the two front-line medications, she was started on continuous dextrose (sugar water) to boost her sugar to the safe range. As she has grown, she’s needed less dextrose and now, at 3½ years old, may be able to get off dextrose all together, according to her team in CHOP’s Congenital Hyperinsulinism Center.

Cardiologists found three small holes in her heart chambers, two ventricular septal defects and one atrial septal defect, that allowed oxygenated and deoxygenated blood to mix in the heart, which can sap energy and delay growth. Two of the holes have closed on their own, and the third is smaller.

Rosalie has had surgery to correct misaligned eyes (strabismus). She sees specialists in the Orthopedic Center for hip dysplasia (loose hip joints) and Gastroenterology for chronic constipation. Some conditions are connected to the tendency for children with Kabuki syndrome to have diminished muscle tone (hypotonia).

Across CHOP, Families Come First

“It seems like every time we come to CHOP, they find something new,” Dara says.

Also on Rosalie’s list of specialists: Neurology, Urology, Otolaryngology, Immunology, the Sleep Center, the Autism Integrated Care Program, Nutrition and the Feeding Clinic. She has been an inpatient numerous times, often for infections; frequent infections are another characteristic of Kabuki syndrome.

One consistent trait Dara sees no matter where within CHOP she and Rosalie visit: a family-first approach.

Doctors need to be willing to listen to parents,” Dara says. “Together, we need to brainstorm different solutions. CHOP is wonderful. Doctors don’t dismiss what I say. They listen and think outside the box. If it wasn’t for CHOP, my daughter would not be alive.

Coming Soon: Special Kabuki Syndrome Clinic

The Rare Disease Program within the Roberts IMGC recognizes that children with Kabuki syndrome need a team of specialists that understands the multifaceted and evolving nature of the syndrome to guide families.

To better serve these families, the RIMGC is launching a special multidisciplinary clinic just for them. In one appointment, they will meet with a clinical geneticist, genetic counselor, endocrinologist, gastroenterologist, immunologist and nutritionist. Additional pediatric specialists join the team as needed by a particular patient. Together, they’ll map out a care plan tailored for each child.

“I’m thrilled,” Dara says. “It will be a significant help for those of us in the Kabuki community. When we get this diagnosis, we’re blindsided. It’s overwhelming. The Kabuki Syndrome Clinic will help families answer the question we all have: What do I do now?”

Dollies and dancing

While CHOP is helping the family figure out the medical side, Rosalie is a busy 3-year-old who loves music, dancing and her baby dolls. “She loves to rock her dolls and give them kisses,” Dara says.

She receives occupational and physical therapy at home, which is helping build up her endurance. While she isn’t speaking much yet, she understands what she hears. “Rosie is high functioning,” her mother says. “She’ll follow easy instructions.”

Some of Rosalie’s other favorite activities are slipping some of her food to the family dog, sitting in a shopping cart and going on short walks.

“We don’t know what the future will bring,” says Dara. “Kabuki syndrome is so odd in that it is different in every child. That’s why I’m so excited CHOP is having a special clinic for our kids. It’s a phenomenal hospital.”

An update on Rosalie

Rosalie, who just turned 5, is a proud preschooler in a neurotypical classroom, where she’s made friends and is enjoying herself. “I was a little nervous, with her differences and that she has a nurse with her, but everyone has been very welcoming,” says Dara. When Rosalie had a meltdown during a joint session with the kindergartners, prompting a few older kids to tease her, “some of her classmates told them, ‘She’s sad now. Leave her alone.’ That warmed my heart.”

One helpful tool has been an iPad with the program iTalk. “We’re learned she can’t hear the ‘f’ sound, which impeded her learning. She couldn’t say, ‘I’m four, I’m five.’ With the iPad, she can touch on the pictures to express herself. She can even form sentences. It really helps limit frustration,” Dara says.

Rosalie still is seen in the Hyperinsulinism and the Kabuki Syndrome Clinics and continues to see several CHOP specialists. Much of her ongoing care is coordinated by the Compass Care Program, a special high-touch program for complex patients.

During one inpatient stay earlier this year, she underwent a fasting study to see that status of her hyperinsulinism. “She was able to fast for 18 hours without having low blood sugars,” Dara says. “I was shocked! We are able to eliminate her dextrose at night. With the monthly lanreotide injection, she hasn’t had a low in forever.”

During that same hospital stay, Compass Care coordinated six specialists to perform various tests back-to-back-to-back when Rosalie was under anesthesia. Cardiology confirmed all three holes in her heart had closed, Audiology confirmed her mild hearing loss was stable, an orthopedic exam confirmed her joints were not dislocating, Otolaryngology made sure her ear tubes were still properly placed and functioning, Ophthalmology found she was extremely nearsighted and has astigmatism, and Radiology performed ultrasound of her liver, at Endocrinology’s request, as lanreotide can affect its function. She also had a new g-tube placed.

The following day she had a swallow study to ensure she was not having silent aspiration, an issue in Kabuki syndrome due to low muscle tone. She passed. Later, she did a sleep study, which confirmed she still can do without treatment for sleep apnea.

“Her health is really good,” Dara says. “Now we’re focusing on getting her IEP [individualized education plan] in place. And she’s continuing with occupational, physical and speech therapy.” Rosalie also receives applied behavioral analysis therapy, to help her learn to manage her autism-related behaviors that impede her learning.

“I don’t know what I would do without CHOP,” Dara says. “The Hyperinsulinism and Kabuki Clinics are a great resource. The Compass Care Program coordinates everything and makes sure all her doctors are on the same page. CHOP understands that a 20-minute appointment doesn’t work for complex kids.”

Originally posted: February 2021