Angelman Syndrome: An Updated Review of Pathophysiology, Diagnosis and Management

The illness now referred to as Angelman syndrome (AS), originally termed the "Puppet Children," was first recorded in 1965 by a British physician named Harry Angelman. Angelman observed that three children with cognitive disability had certain traits: a positive disposition towards people, uncoordinated or spasmodic motions, and limited or absent verbal communication abilities. In 1987, Ellen Magenis discovered two children with notable deletions on chromosome 15. This genetic abnormality was linked to a phenotype characterized by severe ataxia, seizures, and episodes of prolonged and spontaneous laughter. Due to its exclusive imprinting in the brain, the expression of the UBE3A gene is limited to the neurological system, leading to most of the manifestations of Angelman syndrome (AS) being confined to this system. Patients who are suspected of having Angelman syndrome are initially assessed by clinical evaluation using DNA methylation assays, specifically targeting the differentially methylated SNRPN promoter/exon 1 region. The current approach to managing Angelman syndrome is mostly focused on addressing symptoms; however, there are promising gene- based medicines under development. The primary emphasis of medications used in the treatment of epilepsy in Angelman syndrome is on moderate motor or akinetic seizures. Valproate, clonazepam, topiramate, lamotrigine, and levetiracetam have demonstrated potential, whilst carbamazepine, phenobarbital, oxcarbazepine, and vigabatrin have shown limited potential.