Early Detection of Neurodevelopmental Disabilities May Improve Angelman Patients’ Outcomes

Early and careful detection of the spectrum of neurodevelopmental disabilities in children with Angelman syndrome is essential to planning personalized rehabilitation programs and improving outcomes, research suggests.

These findings emphasize the need for early diagnosis, particularly of neurovisual disorders, which can seriously contribute to cognitive impairment and attention deficit.

Of particular note, researchers found that intellectual disability does not seem to be the sole reason why Angelman children experience language difficulties. Another unknown cause, possibly related to alterations in brain structure, is likely behind these issues. 

The study, “Neurodevelopmental profile in Angelman syndrome: more than low intelligence quotient,” was published in the Italian Journal of Pediatrics.

Regardless of whether Angelman is caused by a UBE3A mutation, deletion, paternal uniparental disomy, or imprinting defect, the condition is characterized by common features: developmental delay, movement or balance disorders, speech impairment, and specific behaviors.

Although many studies have documented the cognitive, language, and behavioral characteristics of Angelman, there is no integrated profile of these different areas. In addition, some Angelman features have been poorly investigated, including daily living skills, also called adaptive behavior, and neurovisual problems.

Italian researchers performed a series of examinations in a group of children with Angelman to obtain a comprehensive neurodevelopmental profile of the disease that could be used as a starting point for designing early and personalized interventions.

A total of 10 children from 5 to 11 years old with a confirmed molecular diagnosis (deletion or mutation) of Angelman were included. Children with epilepsy resistant to anti-epileptics or who had an additional disease were excluded.

All participants underwent an evaluation that included both clinical assessments of the patients and parents’ questionnaires to specifically address each area of neurodevelopment. Neurovisual assessments were conducted on ophthalmological features, oculomotor components, visual perception elements, and visual attention.

All children had motor function impairments, including delays in head control, sitting, and walking. The ability to walk seemed to be the most difficult milestone to reach; however, children with UBE3A mutations achieved motor skills sooner than those with a genetic deletion.

Cognitive evaluation detected intellectual disability in all children, as well as communication difficulties (speech sounds, word/gesture comprehension, and production), and symptoms of attention deficit.

Regarding adaptive behavior, communication and daily living skills were the most affected, although children with UBE3A mutations had better personal and gross motor skills.

Language abilities were particularly weak in understanding and expressing skills, as none of the children were capable of pretending play skills or expressive language speech.

“These results let us hypothesize that the lack of expressive language is not simply justified by the severe intellectual disability in AS population. Neither difficulties in interpersonal relationships seem to be the cause of expressive disorders,” the researchers wrote.

None of the participants had normal babbling patterns, suggesting that the cause behind language disabilities could be problems with the articulation of sounds.

Several neurovisual disabilities were also found among children, including refractive errors — abnormal shape of the eye preventing light from focusing directly on the retina — anomalies in the back of the eye, strabismus, and oculomotor dysfunction. No major problems were apparent in patients’ visual perception.

Researchers believe that the presence of refractive errors in all participants underlines the need for an early neurovisual evaluation to diagnose and prescribe optical devices.

“An early correction of refractive errors can ameliorate visual acuity for activities of daily living and finally can promote the development of cognitive functions, as has been documented in patients with other genetic syndromes,” they wrote.

Researchers stress that early identification of oculomotor disorders and early promotion of oculomotor functions may have a positive effect on attention deficit.

These findings highlight that Angelman syndrome has a complex clinical profile comprised of several areas interacting with each other and playing a negative role on global development.

“… An early and careful assessment of motor, neurovisual, cognitive, linguistic and attention abilities should be essential for a correct identification of strengths and weaknesses of this clinical population so as to plan tailored rehabilitation programs, based on the promotion of motor milestones, neurovisual function and communication abilities during the first stages of life,” the researchers concluded.