Angelman syndrome with atypical presentation mimicking cerebral palsy: diagnosis and treatment challenges

Natã N.J. Graça, Department of Internal Medicine, Universidade do Oeste Paulista, Campus Guarujá, Guarujá, Brazil
Márcio L. Duarte, Department of Radiology, Universidade de Ribeirão Preto, Campus Guarujá, Guarujá; Department of Radiology, Diagnósticos da América S.A., São Paulo, Brazil
Márcia Fernández-Cascardi, Department of Pediatric Neurology - Clínica Neurosantos, Santos, Brazil

Background: Angelman syndrome (AS) is a rare genetic disorder caused by the lack of expression of the UBE3A gene, inherited maternally, and is associated with an abnormal chromosome 15q11-q13. Affects 1 in 12,000-20,000 individuals and is more commonly diagnosed in childhood, although some cases are missed in adulthood. This condition, which affects both genders equally, often is undiagnosed due to errors or underreporting. This case involves a patient with AS, initially misdiagnosed as cerebral palsy, presenting with severe developmental delay, autistic behaviors, hypotonia, and epilepsy. Clinical case: We describe the case of a 3-year and 10-month-old male patient with a family history of autism spectrum disorder and attention deficit hyperactivity presented with motor delay, severe hypotonia, brachycephaly, absence of trunk control, difficult- to-control epilepsy, and severe developmental delay (unable to walk or speak). Initial observations revealed he could not sit or crawl and had difficulty swallowing. He was prescribed risperidone and had follow-ups for ongoing issues. In 2022, he experienced a tonic-clonic seizure and was diagnosed with chronic non-progressive encephalopathy and epilepsy, leading to valproic acid treatment. Subsequent seizures led to adjustments in his medication regimen, including adding clonazepam, phenobarbital, and levetiracetam. Genetic testing confirmed a deletion in the Prader-Willi/AS critical region on chromosome 15. The patient is currently stable. Conclusions: AS is characterized by developmental delays, speech impairment, ataxia, and seizures, along with characteristic behaviors such as inappropriate laughter. The comorbidities associated with AS, such as seizures and ataxia, significantly increase the risk of injuries and accidents, leading to higher morbidity and mortality in patients.

Keywords: Angelman syndrome. Seizures. Ataxia. Epilepsy.