November 5, 2012
Rare Disorder Takes Heavy Toll
By Carolyn Gutierrez
For The Record
Vol. 24 No. 20 P. 22
Technology and the good will of others help ease the burden of Angelman syndrome.
A rare genetic disorder occurring in approximately one in 15,000 live births, Angelman syndrome (AS) can cause severe intellectual disability, seizures, motor challenges, an absence of speech, and sleep difficulties. One of its main characteristics is perhaps its most bittersweet: Individuals with AS are known for their happy demeanor, frequently smiling and laughing.
AS can profoundly impact affected individuals and their families. “Individuals with AS are usually very pleasant and enjoyable to work with, but their physical and cognitive limitations can be very challenging,” says Anne Wheeler, PhD, an assistant clinical professor of psychiatry at the University of North Carolina at Chapel Hill and co-coordinator of the Comprehensive Angelman Syndrome Clinic at the Carolina Institute for Developmental Disabilities. “There is a need for more professionals to understand AS and know how to best support the individual and their caregivers.”
AS occurs when the UBE3A gene, which is necessary for normal brain development, is missing from the maternal chromosome 15. “There are four genetic types of AS—all result in loss of UBE3A,” Wheeler says. “The most common is a genetic deletion—presumably a random occurrence where the needed part of the maternal chromosome 15 is deleted. This accounts for about 68% of cases.”
In approximately 13% of AS cases, there is an abnormality on the UBE3A gene itself. In 6% of cases, there is an error in which the imprinting center on chromosome 15 fails to effectively “turn on” the UBE3A gene. “Three percent of cases are due to paternal uniparental disomy,” adds Wheeler, “which is essentially when the child inherits two copies of the paternal chromosome 15 and no maternal copy.”
Like AS, Prader-Willi syndrome (PWS) also originates from chromosome 15. The difference is that AS occurs when the gene is missing from the maternal leg of chromosome 15, whereas PWS occurs when the gene is missing from the paternal leg of chromosome 15. According to Wheeler, however, the phenotypic results are very different.
“Individuals with PWS have borderline to low-average cognitive functioning—they are much less severely impacted when it comes to learning,” she notes. “Individuals with AS have very severe cognitive impairment, usually do not develop any or very little speech, have a high risk for seizure disorder, and often have mobility challenges.”
One Mother’s Story
Almost immediately after their first child, Tatum, was born, Aven and her husband, Justin, sensed their baby was different from other infants. “Early on, we just knew something wasn’t quite right, but we couldn’t put our finger on it,” Aven says. “During Tatum’s first five months, we were running to doctors and hospitals, probably several times a week, because we were worried. She had constant movement and episodes where her eyes would roll back into her head. She had decreased muscle tone—it was scary.”
Most of the clinicians who saw Tatum during the first few months of her life either could not make sense of her symptoms or decided that nothing was wrong.
When Tatum was about 4 months old, the Dillsburg, Pennsylvania, family drove to the Children’s Hospital of Philadelphia where Tatum was tested for seizures, one of the most common and dangerous symptoms of AS. Although she tested negative, the hospital recommended that a neurologist see Tatum.
“The neurologist suggested we get genetic testing,” Aven says. “They took a blood test for Tatum and saw that she was missing certain genes on chromosome 15, and then they took a sample of my blood and my husband’s blood to see if it was on the maternal chromosome or the paternal chromosome. Because it was on the maternal chromosome, it was Angelman syndrome.”
A few weeks later, at 5 months old, Tatum received a diagnosis of AS. To further complicate matters, Tatum also had heart problems unrelated to AS and had to undergo open-heart surgery.
Despite the hardship of Tatum’s diagnosis and her fragile condition, “It was a relief to know what we were dealing with,” Aven says. “I think it was scarier to not know and kind of think the worst than to find out what was actually going on. From there, we dealt with the diagnosis the best way we knew how. The Angelman Syndrome Foundation was the first place we found where we could actually hear other people’s stories, connect with parents, and find out what it was that Tatum had.”
The Angelman Syndrome Foundation, created to foster awareness and treatment of the condition through education, research, and support, is celebrating its 20th anniversary this year.
“During the past 20 years, we’ve raised nearly $11 million in support of all individuals within the Angelman syndrome community,” says Eileen Braun, the foundation’s executive director who is the mother of a 22-year-old daughter with AS. “Half of these funds that we’ve raised have gone directly into funding research grants, and nearly 35% of these funds have provided direct support to those individuals that are affected by Angelman syndrome.”
According to Braun, the foundation has provided information and resources to more than 250,000 people. “We have been able to amass an army of about 7,000 volunteers. That averages out to about one volunteer a day for the last 20 years, and we’re very, very proud of that,” she says. “We couldn’t do it without our volunteers.”
The Angelman Syndrome Foundation has a full-time resource specialist on staff to help families locate local, state, and national resources. It also addresses numerous complicated issues ranging from financial assistance and insurance to medical care. “We have additional resources for families, such as budgeting tools, scheduling tools, and information on how to research treatment options for the symptoms associated with Angelman syndrome,” Braun notes.
The foundation helps families sort through the often overwhelming amounts of information about AS on the Internet and verify its veracity. “There’s a lot of misinformation out there, and we just want to make sure that people aren’t taken advantage of,” Braun says. “Sometimes families will call and they will want to mortgage their home over a treatment that has not even been proven and is not really a viable treatment option.”
Current treatments for AS, for which there is no cure, focus primarily on relieving the major symptoms. People with AS are generally given medications such as valproic acid, topiramate, and lamotrigine for seizures and occasional sedatives for sleep difficulties. Physical and occupational therapies assist with teaching basic functional skills such as toileting and feeding and also can improve sleep, balance, and motor skills.
Relationship to Autism
Experts in the AS community are concerned with the disorder being misdiagnosed as autism. There is a growing discussion among medical professionals that AS is within the autism spectrum and that there are a high percentage of individuals with AS who also have autism. Although there is a cohort of people with AS who manifest similar behaviors as those with autism, given the severity of their developmental and communication impairments, it is difficult to diagnose.
“Some of the characteristics that do overlap between the two disorders really have to do with some of the obsessive-compulsive, repetitive-type behaviors you would see in autism,” Braun says. “Although we typically describe individuals with Angelman syndrome as being very social, engaging, and seeking out attention, in this cohort of individuals with Angelman syndrome and autism, they tend not to be as social and may actually find social situations to be aversive. They become incredibly anxious; they become very overstimulated and have a very difficult time managing their behavior in a highly stimulating social situation. Those are some of the areas where we might see that overlap.”
Interestingly, Braun notes that one of the major therapies for autism, applied behavior analysis, has been found to be extremely effective for individuals with AS.
New Technologies for Communication
As with autism, one of the most crucial concerns facing families living with individuals with AS is teaching communication skills. People with AS may communicate with their families through eye gaze, physical touch, and modified signs. Depending on the severity of the individual’s disorder, communication techniques can be taught incrementally to those with AS.
“Some individuals with AS can use simple signs, gestures, and vocalizations to communicate,” Wheeler says. “However, their motor challenges and cognitive impairments make anything beyond simple communication of wants and needs very difficult. Often parents are attuned to their child’s communication attempts, but those who know the individual less well will have difficulty understanding what they are trying to communicate.”
The tool that is proving to be the most revolutionary communication device for those without a voice is the iPad. With assistance from the Angelman Syndrome Foundation, 2-year-old Tatum has just started learning to use an iPad communication application called Proloquo2Go. Comprising more than 14,000 symbols, the augmentative communication application provides easily accessed visual cues that can help people with very limited speech communicate. The application can be customized for each individual’s needs and cognitive level. A girl’s or boy’s voice can be selected to “speak” for the child.
“It’s nice because it’s really basic for beginners, but it will get more complex as Tatum gets older,” Aven says. “She can start off now at 2 years old and use it up until she’s an adult, so it grows with her. Right now, every time she starts to eat, we have her push the button ‘I am hungry.’”
Wheeler notes that for individuals with AS who have the basic ability and intention or desire to communicate, “Technologies such as the iPad can assist with communication and learning basic development skills such as cause and effect.”
Perhaps most importantly, as iPads and other touch-screen technologies become ubiquitous, children with special needs can more easily fit in with their peers when they communicate through these tablets. “One of the great things about this technology,” Braun says, “is that it becomes more inclusive for them. In the past, some of the voice output devices that individuals used separated them and made them seem different. Whereas now, an individual can carry along their iPad, their iPod touch, and they are doing the same thing that everybody else around them is doing and they feel included. They feel like, ‘I’m not so different from my brother and sister and my friends at school because they are all using these devices, too.’ It’s an incredible communication tool for these individuals. These type of technologies have really opened the doors for individuals with Angelman syndrome.”
Unfortunately, because there is a fairly wide range of cognitive severity within the disorder, not all people with AS have the capability to use these technologies.
In addition to breakthroughs in communication technologies for people with AS, recent studies funded by the Angelman Syndrome Foundation have shown great promise. Researchers at the University of North Carolina School of Medicine discovered a possible root cause of seizures by tracking the neuronal activity in the brains of mice with AS. Using electrophysiological methods to record the activity of brain cells, the researchers found an imbalance between neuronal excitation and inhibition in mice with AS. The neurotransmitters that were sent from inhibitory neurons to stop excitatory neurons from increasing their activity were found to be defective, thus disrupting the balance between inhibitory and excitatory neurons needed for regular neuronal function. This hyperexcitable state in the neurocircuitry is thought to bring on seizures in many individuals with AS. The lack of regulation in the brain’s neuronal activity also may contribute to the cognitive deficits found in the disorder.
Because 90% of people with AS have been shown to have seizures—with some individuals experiencing hundreds of seizures daily—they are a prime focus for researchers. “We have a great group of researchers at the University of North Carolina that are working fast and furiously on Angelman syndrome, so we expect to continue to see great results,” Braun says.
In another foundation-funded study addressing seizures, scientists at Massachusetts General Hospital found that a dietary treatment, specifically a low-glycemic index treatment, reduced the number of seizures by more than 80% in five of six children with AS over a period of four months. When those five children remained on the diet after completing the study, they were found to have a 90% reduction in seizures after one year.
The children in the trial, ranging from ages 1 to 5, were given a high-fat, low-carbohydrate diet. Braun explains that by reducing their sugar intake, “It keeps their insulin levels low and stable across the day—that really seems to stabilize the seizures and, in some individuals, actually helps eliminate seizures. It’s incredibly powerful.”
Despite a 90% chance that she would develop seizures, Tatum has not. However, she does experience some of the sleep difficulties that go along with AS. To help the toddler transition from her crib into a “big girl bed” and to give her family peace of mind, SleepSafe Beds, in conjunction with the Angelman Syndrome Foundation and Wish Upon a Hero, has donated a custom-made bed that is padded and secure so that if Tatum does begin to experience seizures, she will be safe.
“There’s a lot more to think about when you have a child with special needs,” Aven says. Because children with AS struggle with walking, mobility is one of their biggest challenges. To help her keep up with her 1-year-old sister, Adelina, Tatum uses a special walker. Aven says the device has been a great source of excitement for Tatum, as it enables her to more easily interact with her little sister and other playmates.
Helping Tatum adjust to her walker, teaching her how to use the iPad application, scheduling her numerous daily therapy sessions, and following all the therapists’ recommendations and suggestions can be a challenge for the young family.
“It takes a lot of extra work for her to learn the things most parents take for granted,” Aven says. “With Tatum, there’s a lot more repetition and a lot more work, but it’s equally rewarding. We’re so proud of her—maybe even more proud of her because she’s so determined and motivated to learn to do the things her sister can do even though it’s harder for her. Day to day, we’re just trying to get her to be as independent as she can.”
AS is a lifelong disorder, and individuals live well into their 60s and 70s but require constant care. The physical, emotional, and financial toll on families and caregivers can be daunting. “You see these families with such integrity and such dedication to their loved one,” Braun says. “That’s why we are here to support them. We need to help them on a daily basis, but we also need to help them for the future, which is where the research comes in.”
For Tatum, the simple act of greeting her friends in her walker will do for now. “It’s been a journey,” Aven says. “Tatum is so easygoing. We bring Tatum to nursery school at church, and she just starts walking to her class all by herself in her walker and all the kids run up to kiss her and she giggles. She’s very social and loving. She’s a joy.”
— Carolyn Gutierrez is a freelance writer based in New York City.