Table 3 Natural history of select Angelman syndrome symptoms
From: Unmet clinical needs and burden in Angelman syndrome: a review of the literature
Infancy/Early Childhood | Middle Childhood/Adolescence | Adulthood | Current Standard of Care | |
|---|---|---|---|---|
Movement disorders | ▪ Hypotonia/“floppy infant” observed in ~50% [6] ▪ Feeding issues/Poor suck in infancy [6, 8, 15, 16] ▪ All motor milestones delayed [24] | ▪ Tone improves in most, but ~25% have persistent hypotonia and ~30% have hypertonia [6] ▪ Atypical or ataxic gait is common [10, 23, 25, 26] ▪ Coactivation of muscles, muscle weakness, and sensory-motor integration are also common [22] ▪ Developmental skills tend to plateau at 24–30 months [24] ▪ Oral motor challenges are also pervasive, with tongue thrusting, sucking and swallowing disorders, frequent drooling, excessive chewing, mouthing behaviors, and feeding difficulties reported in 20%–80% [8, 15, 16] ▪ Full toilet training obtained for about 30% of individuals with AS, although age of obtaining this milestone varies [8] | ▪ Increase in scoliosis [8] ▪ Increases in tremor and NEM may result in loss of previous obtained skills [16, 28] | ▪ Physical and occupational therapy [12] ▪ Physiotherapy [12] ▪ Bracing as needed [12] ▪ Increased activity and diet to prevent obesity [12] |
Speech/Communication | ▪ Less cooing and babbling in infancy [15] ▪ None or very little oral speech acquisition [35] | ▪ No increases in verbal output [35] ▪ Development of gestures and other methods of communication [35, 36, 41, 42] | ▪ No increases in verbal output [35] ▪ With improvement in attention span in adulthood, some increases in nonverbal communication [12] ▪ Communication challenges thought to contribute to aggression and anxiety [75] | ▪ Augmentative and alternative communication systems [34, 44] |
Behavior | ||||
Smiling/Laughing | ▪ Early, persistent social smile reported as early as 1–3 months of age [50] | ▪ More socially appropriate smiling/laughing [53] | ▪ Behavior-based interventions such as applied behavior analysis or discrimination training [77, 80,81,82] ▪ Increasing communication outputs [80] ▪ Psychopharmological treatment, including anxiolytic/anti-depressants (e.g., buspirone, guanfacine, clonidine); SSRIs (e.g., fluoxetine, sertraline, citalopram); antipsychotics (e.g., risperidone, aripiprazole, olanzapine); antihypnotic/stimulant (e.g., atomoxetine, methylphenidate, dexmethamphetamine) [16, 75] | |
Hyperactivity | ▪ Hyperactivity reported to occur in nearly all young children with AS [15, 60] | ▪ Hyperactivity/excitability the most prominent and severe behavior reported [13, 60] | ||
Aggression/Irritability | ▪ Physical aggression has been reported in up to 73% of adolescents with AS [74] | ▪ Physical aggression/irritability increase in adulthood [75] | ||
Autism symptoms | ▪ Comorbid autism diagnosis reported in up to 80% [62,63,64] ▪ Those with AS and comorbid ASD score lower on measures of language, adaptive behavior, and cognition, and have a slower rate of growth over time than those with AS without ASD [63] | |||
Anxiety | ▪ Anxiety increase in adulthood [75] | |||
Other behaviors (e.g., repetitive behavior, mouthing) | ▪ Self-injurious behaviors increase in adulthood [75] | |||
Sleep | ▪ Sleep improves for some but sleep problems continue for a significant percentage [12, 75, 85,86,87] ▪ The most common type of sleep problem is insomnia with 35%–60% of individuals with AS being described as having difficulty initiating sleep and/or maintaining sleep and reduced total sleep time [61, 85, 87, 88] ▪ Quality of sleep is also problematic, with reduced sleep efficiency found via sleep polygraph in children with AS compared with controls [88, 89] | ▪ Sleep improves for some, but sleep problems continue for up to 72% [12, 75, 85,86,87] | ▪ Improvement of sleep environment [86, 87, 100] ▪ Adjusting sleep-wake schedules [94, 100] ▪ Reinforcing bedtime routines and independent sleep initiation [97, 100] | |