Challenges Facing Adults With Angelman Detailed in Study

Despite being relatively healthy, adults with Angelman syndrome should be carefully monitored, particularly for weight control, vision and gastrointestinal issues, behavioral and sleep problems, and epilepsy, a study suggests.

According to its authors, findings from this study, reported to have enrolled the largest and oldest group of adults with Angelman to date, provide valuable insights into disease’s course in adulthood and may be useful in developing therapies for these patients.

“Clinical aspects of a large group of adults with Angelman syndrome” was published in the American Journal of Medical Genetics.

Angelman syndrome is a genetic neurodevelopmental disorder caused by the loss or malfunction of the maternal copy of the UBE3A gene in neurons in specific areas of the brain. The disorder is usually associated with severe intellectual disabilities, difficulty speaking, loss of movement control (ataxia), and epileptic seizures that fail to respond to anti-seizure medications.

Although many studies thoroughly describe Angelman’s main clinical features, most have focused on children and infants with this disease.

“Far less is known is about the course of the syndrome in adulthood,” the investigators wrote, adding that studies in adults often enrolled a small number of patients, who were mostly in their 20s.

Researchers in the Netherlands aimed to characterize the syndrome’s clinical features in a larger group of older adults with Angelman.

The study, which took place from 2015 to 2018, included data on 95 adults (48 men and 47 women), ages 18–83, with a genetically confirmed diagnosis of Angelman. Their mean age was 31.6.

Patients were recruited through the Dutch Angelman parents association and the Dutch Society of Physicians for persons with intellectual disabilities. Those visiting the outpatient clinic of a Dutch center for neurodevelopmental disorders were also asked to participate.

Investigators gathered patient data by analyzing medical records, interviewing and collecting information from questionnaires given to their parents and/or caregivers, and performing a physical examination.

Birth for most patients followed an uneventful and full-term pregnancy, data revealed. In 82% of the cases, however disease symptoms first became evident in the months after birth. More than half (65%) of the patients as infants experienced feeding difficulties, including frequent vomiting, difficulties swallowing, and lack of a sucking reflex.

Although Angelman symptoms manifested early on in life, the median age of diagnosis for this group was 6.8 years. However, when considering only younger patients — those 18 to 29 — diagnosis came at an earlier median age, 2.5 years, “probably reflecting improved availability of genetic testing.”

Most parents and caregivers reported patients had inappropriate behaviors, which included hair pulling, screaming, hitting, nail and skin picking (86%), and biting. Most patients were also hyperactive in childhood, but became increasingly calmer over the years, parents and carers reported.

A history of epileptic seizures (89.4%) existed for most patients, and among them, 80% were taking anti-epileptic medications when they enrolled in the study. In 10.7% of the cases, these medications failed to control patients’ epileptic seizures.

At the time of the study, more than half (57%) of the patients also experienced sleep problems, according to reports from parents and/or caregivers. A third (30%) were reported to have visual impairments, but only 18% wore glasses.

Most participants were also able to walk — either with support or unaided — at some point in their lives, and typically started walking at around age 4. However, about a third (27%) were showing a decline in mobility at the time of the study. Among those 40 and older, difficulties with mobility were common, reported in 84% of the cases.

Nearly all (90%) the adults had constipation, and almost half (45%) had difficulties swallowing food or choked while eating. About a third had gastroesophageal reflux.

An insatiable appetite or “greedy” eating was noted for about half of these adults, while 10% were described as poor eaters.

Patients’ physical examination revealed that 1 in 10 men in the group were considered underweight by body mass index standards (BMI lower than 18 kg, or 39.7 lbs, per m²); none of the women were underweight. Although more than half of the patients had a normal body weight, 37% were overweight (BMI of at least 25 kg, or 55.1 lbs, per m²). Among overweight patients, one-third were classified as obese (BMI of 30 kg or higher).

Most patients had some degree of scoliosis. It was mild in most cases (64%), but severe in 22%. A total of 14% of the patients had surgery to correct their severe scoliosis.

“Adults with AS [Angelman syndrome] are relatively healthy, but still have some serious debilitating health problems. Care for adults with AS should focus on monitoring weight, visual functioning and management of epilepsy, behavioral and sleep problems, communication, reflux, and constipation. Frequent monitoring of the spine and timely intervention when scoliosis is developing is important as well as the monitoring of mobility,” the researchers wrote.

“This knowledge is required to improve care for adult individuals with AS and to evaluate future therapies for this group,” they added.