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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]
▪ NEM usually starts in adolescence [16, 28]
▪ 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]
▪ Receptive language better than expressive [37, 45]
▪ 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]
▪ Promotion and enhancement of natural gestures [46,47,48]
Behavior
Smiling/Laughing ▪ Early, persistent social smile reported as early as 1–3 months of age [50] ▪ More socially appropriate smiling/laughing [53] ▪ Decline in duration of smiling and laughing [54,55,56] ▪ 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] ▪ Hyperactivity decreases in adulthood [12, 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 issues peak between 2 and 9 years of age [84, 86] ▪ 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] ▪ Melatonin [93,94,95,96,97]
▪ Improvement of sleep environment [86, 87, 100]
▪ Adjusting sleep-wake schedules [94, 100]
▪ Reinforcing bedtime routines and independent sleep initiation [97, 100]
▪ Seizure medications [99, 116]
  1. AS Angelman syndrome, ASD autism spectrum disorder, NEM non-epileptic myoclonus, SSRI selective serotonin reuptake inhibitors