Angelman syndrome



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Angelman syndrome (AS) is a neurogenetic disorder characterized by severe intellectual deficit and distinct facial dysmorphic features. Prevalence of AS is estimated to be 1/10,000 to 1/20,000 worldwide. Patients with AS appear normal at birth. In the first 6 months of the neonatal period, feeding difficulties and hypotonia may occur, followed by developmental delay between 6 months and 2 years of age. Generally from 1 year of age, the typical features of AS develop: severe intellectual deficit, absent speech, outbursts of laughter with hand flapping, microcephaly, macrostomia, maxillary hypoplasia, prognathia and neurological problems with a puppet-like gait, ataxia and epileptic seizures with specific electroencephalogram (EEG) abnormalities (triphasic delta activity with a maximum over the frontal regions). Other signs that have been described include a happy demeanor, hyperactivity without aggression, short attention span, excitability and sleeping problems with decreased need to sleep, increased sensitivity to heat, attraction to and fascination with water. With advancing age, the typical features of the disease become less marked because of facial coarsening, thoracic scoliosis and mobility problems. Thoracic scoliosis is reported in 40% of AS patients (mostly females). Seizures remain present in adult patients, but hyperactivity, short attention span and sleeping problems improve. In patients with deletion of the 15q11 region, iris and choroidal hypopigmentation are common. Different genetic mechanisms may cause Angelman syndrome, such as deletion of the 15q11.2-q13 critical region (60-75%), paternal uniparental disomy (2-5%), imprinting defect (2-5%) and mutation in the UBE3A gene (10%). In a group representing 5-26% of patients, the genetic defect remains unidentified. Diagnosis is based on clinical and EEG findings, and can be confirmed in most cases by cytogenetic and molecular testing. The typical EEG pattern can be helpful for diagnosis and differential diagnosis includes hypsarrhythmia in West syndrome or the petit mal variant pattern in Lennox-Gastaut syndrome (see these terms). Other differential diagnoses include Rett syndrome, Mowat-Wilson syndrome, X-linked alpha-thalassemia-intellectual deficit syndrome (ATR-X), and 22q13 deletion syndrome (see these terms). Genetic counseling is advised as the recurrence risk varies between 0 and 50%, depending on the underlying genetic mechanism. Management includes physical, occupational and speech therapy including nonverbal methods of communication. As patients commonly develop seizures at a very young age, anticonvulsant medication is required. Sedative medication can be given in patients with severe sleep disorders. Visual function should also be monitored. In adulthood, patients become less active and have a tendency towards obesity. Mobility decreases with joint contractures leading to difficulties in walking and some patients become wheelchair bound. Life expectancy appears to be normal although autonomy is never reached.


Tomado de Orphanet