Date Published: March 6, 2020
When 3-year-old Kennedy Manning walked into her first appointment at the Duke Center for Autism and Brain Development, she immediately began banging her head against the metal corner of the bedframe. “It took me aback — it was out of nowhere,” says Dr. Nathan Copeland, a psychiatrist at the center who still sees Kennedy. “I had never seen that before. She didn’t seem upset or agitated.”
The violent behavior wasn’t surprising for Kennedy’s parents, Karah and Ian. Kennedy already had a long history of self-injury, beginning when she was just a year and a half old. “She bites herself, hits herself, slams herself against the floor or the wall or another person, if they are holding her,” Ian says. “She will be walking and mid-stride, pull her knee up and knee herself in the face. She’s given herself black eyes and pulled teeth.”
It’s one of the biggest challenges the Mannings have faced with Kennedy, who is now 5. “That has made us the most heartsick. It has been all-consuming,” her mother says.
Self-injury is one particularly challenging aspect of a puzzling genetic condition that Kennedy was diagnosed with at 3 years old. The condition is caused by a change in a gene called CACNA1D. Symptoms can vary widely, including autism, intellectual disability, developmental delay, seizures, and high blood pressure and low blood sugar very early in life.
Kennedy’s condition is extremely rare — only about a dozen people have been described in the medical literature to date. Scientists and doctors don’t yet know why the symptoms vary so much from person to person.
But they do have some insight into CACNA1D’s job in the cell – it helps to control the flow of calcium, which is important for sending signals between brain cells. Jörg Striessnig, scientist at the University of Innsbruck in Austria, has studied several of the CACNA1D changes that are linked to autism. His team found that some of the changes allowed too much calcium to get into cells. This can disrupt normal communication between cells.
“Too much or too little calcium coming into brain cells, especially as the brain is developing, can be harmful to brain growth,” says Anjali Rajadhyaksha, a scientist at Weill Cornell Medical College who works with Striessnig. “That could result in these various autism-related symptoms.”
A Relief and a Blow
Kennedy’s symptoms first appeared when she was a baby. Unlike her older siblings, she was withdrawn, not connecting with the world around her. “It was like she was in a sensory deprivation tank,” Karah says. She failed to meet developmental milestones. Her delays were severe enough that she qualified for physical, developmental, and occupational therapy before her first birthday. She also showed signs of autism.
The Mannings went through two years of doctor’s visits and medical and genetic tests before finally getting a diagnosis. A test known as exome sequencing, which looks at the parts of the genome that produce proteins, revealed a change in the CACNA1D gene. Exome sequencing is often used in research, but it is still fairly new in clinical practice. Doctors may suggest exome sequencing when other genetic tests have failed to find an answer.
The diagnosis was both a relief and a blow. Because so few people have been diagnosed with the condition, doctors know very little about the long-term outcomes for people who have it. That is especially hard for Kennedy’s family. “There are no support groups or articles talking about what these people’s lives are like 20 years from now,” Ian says. “We have nothing to compare her against. We have no way of knowing if she’ll be able to live an independent life.”
Kennedy is now 5 years old and loves toys that play music and roughhousing with her siblings. She is non-verbal but has learned to communicate in other ways. When she’s hungry, she takes her mother’s hand and walks her to the pantry to get a snack. “I don’t know how all that food fits in her itty bitty body, she loves to eat,” Karah says.
Kennedy was diagnosed with autism soon after her genetic diagnosis. As a baby, she seemed cut off from her surroundings. But with therapy, Kennedy has become more aware of what’s going on around her — particularly with people. “She is very much attuned to people’s feelings,” Karah says. “If she meets someone for the first time, you can tell she will like them if they are happy. But if they’re really tense, anxious, aggravated, she mimics those feelings, her whole mood will change.” She loves when her family hosts family dinners. “She gets really energized by that, she yells out in excitement,” Karah says. “She likes to be touched and tickled and smiles very easily.”
When Karah talks to people about Kennedy, she emphasizes Kennedy’s genetic diagnosis over autism. Kennedy has different needs than children who have autism only, and her mother wants teachers and caregivers to understand that. “People have preconceived ideas of what autism means, what her capabilities should be,” Karah says. “Having multiple diagnoses sort of makes people set aside their preconceived notion of what she needs.”
Feeling Like an Island
The Mannings learned about SPARK when the family was still searching for a diagnosis. Karah had contacted local universities and research institutes in her area, looking for studies that might help them find the source of Kennedy’s issues. “We felt like the cost of getting all of this testing done, the cost of all the visits was incredibly expensive, and we have really good insurance. How are we going to pay for all of this therapy, all these tests?”
After learning of Kennedy’s diagnosis, the Mannings were particularly interested in participating in research because there was so little information about her condition. “We have never met another family who has this diagnosis. We have never met a specialist who met another kid with this diagnosis,” Karah says. “We sort of feel like an island.”
The Mannings also know that the field of genetics is changing rapidly and that more people will likely be diagnosed with the condition as access to genetic testing improves. “To me, research is going to be the only avenue by which we find new ways of helping those children, like Kennedy, who can’t speak for themselves,” she says.
Soon after the Mannings enrolled in SPARK, Karah joined SPARK’s Community Advisory Council, a group of family members and adults who have autism and provide feedback on SPARK’s research and community outreach. She also serves on the Participant Access Committee for SPARK’s Research Match, a program that connects scientists that are studying autism with families that are interested in research. “We look at whether a study would be of interest to participants, if it’s a sensitive topic, the requirements of the study, potential compensation,” Karah says. “It’s cool to see all the ways people are approaching the subject.”
Striessnig is hoping to build a network connecting families in Europe that have changes in CACNA1D. He says that talking with parents can be very helpful for better understanding the symptoms that go along with the gene change. “We hardly get access to parents, so we often don’t get firsthand information,” he says. “We want to connect families with scientists and invite patient organizations to our meetings.”
Self-injury is still a major challenge for the Mannings. Kennedy goes through manageable periods where she seems very happy and self-injury is at a minimum. “Then for no particular reason, she will nose dive and go through a period of 3 to 6 months where it is completely uncontrollable,” Ian says. “There is no discernable reason for why it starts or stops. We are stumped.”
Unfortunately, self-injury can be a common problem in autism. Research suggests that about one in four people who have autism engage in this kind of behavior. The risk is higher in those who have more severe intellectual disability and those more prone to repetitive behaviors.
Kennedy’s case is somewhat unusual. Though the causes of self-injury in autism are still poorly understood, caregivers can often figure out why someone is engaging in this behavior. A child may hurt themselves in an attempt to communicate or for sensory stimulation. Children who are non-verbal and can’t tell others how they feel may try to relieve pain by redirecting it in a way that they can control.
But try as they might, Kennedy’s family and other caregivers couldn’t find an obvious reason for her behavior. She has undergone different medical tests to try to find a medical reason for why she is hurting herself, with no clear answers. “We truly have no way of knowing what’s at the bottom of it,” Karah says.
Self-injury can be difficult to treat, and Kennedy’s case has been particularly challenging.
Medication has been helpful, though finding the right balance is difficult. “In general, she is doing much better than when I first saw her, with far less self-harm and stimming,” Copeland says. “She is still very functionally impaired, but as far as quality of life, for her and for her family, things seem to have gotten better.”
The Mannings hope to see more research on the motivators for self-injury. “A lot of people are dealing with self-injury, but there are not a lot of universal ways to address it, especially among young non-verbal kids like Kennedy,” Ian says. It affects the whole family. “Because of her actions, we can’t take family vacations. There are a lot of things our other kids can’t do because of that, but we have hope that with time and more research, we’ll be able to better meet Kennedy’s needs.”
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