Behaviorally, patients tend to sleep more regularly and become less excitable with age, although aggression and frustration increase because of continued communication difficulties that significantly impair quality of life. Danger perception and activities of daily living continue to be challenges; thus, patients generally require ongoing supervision and are unable to live independently. The life span is not greatly reduced.2
Clinical suspicion of Angelman syndrome tends to arise around age 3 years, when the characteristic behavioral changes predominate over the nonspecific neurological signs seen in infancy (such as microcephaly, flat occiput, protruding tongue, seizures).5,15 Before this age, mild and moderate cases tend to remain undiagnosed. 19 Conditions with which Angelman syndrome is commonly confused are loosely organized as follows:
- Single-gene conditions (Rett syndrome, Gurrieri syndrome, and N5, N10-methylenetetrahydrofolate reductase deficiency).
- Symptom complexes (cerebral palsy, Lennox-Gastaut syndrome, autism spectrum disorder, pervasive developmental delays, and encephalopathy).
- Microdeletions/duplications of chromosome regions 2, 4, 15, 17, and 22.11,12,20
Angelman syndrome is characterized by an abnormal childhood EEG with the following possible changes:
- Rhythmic 2- to 3-Hz triphasic delta waves accentuated over anterior regions and superimposed by interictal epileptiform discharges (most commonly observed).
- Persistent, rhythmic 4- to 6-Hz activity not associated with drowsiness.
- High-amplitude 3- to 4-Hz spike and sharp waves in posterior regions, elicited by eye closure.21
These EEG changes are highly specific to Angelman syndrome and can be helpful for diagnosis in the context of clinical features consistent with the condition.22 There are no significant differences between the EEGs of affected patients who suffer from seizures/epilepsy and the EEGs of those who do not. EEG changes tend to become less pronounced by age 9 years.13
The diagnosis of Angelman syndrome can also be confirmed with genetic testing according to a specific diagnostic algorithm involving DNA methylation testing, FISH and UBE3A mutation testing; however, normal results do not exclude the condition, because of the potential for class V defects.2,12
CT/MRI scans and results of blood, metabolite, and urine tests are usually unremarkable.5
Because no known cure for Angelman syndrome exists, management goals are to improve the quality of life by relieving active symptoms and preventing disease progression. A multidisciplinary team approach is encouraged to manage the various aspects of the syndrome. 2 Early special education programs are vital since communication difficulties are often the most disabling feature of this syndrome.2 Involvement of a pediatric neurologist is often required because seizures can be especially difficult to control in early childhood. Valproate, clonazepam, phenytoin, and lamotrigine have been shown to be effective antiepileptic drugs.23 In adult patients, physiotherapy and occasionally orthopedic surgery may be needed to manage contractures. Finally, because a variety of genetic mechanisms can underlie Angelman syndrome, medical geneticists and genetic counselors play an important role in organizing genetic testing and educating patients and parents about recurrence risks.12 This patient's management team included a general pediatrician, a developmental pediatrician, a pediatric neurologist, a pediatric pulmonologist, a pediatric ophthalmologist, a geneticist, a physiotherapist, and a speech therapist.
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