Dados do Trabalho

Título

COMPLEXITY IN THE MANAGEMENT AND FOLLOW-UP OF ANGELMAN SYNDROME: A SERIES OF 4 CASES

Apresentação dos casos

Four patients, three boys and one girl, were referred to the pediatric neurology clinic due to delays in neuropsychomotor development (DNPM) noticeable by six months of age, associated with epileptic seizures in three of them. The first patient experienced epilepsy initially treated with valproic acid, which induced ataxia, leading to a switch to levetiracetam with good response. The second patient had epileptic seizures with behavioral arrest, and valproic acid was started, but it also induced ataxia and was replaced with topiramate, achieving adequate control. The third patient had tonic epileptic seizures and was treated with levetiracetam. The female patient did not present with epileptic seizures. In all cases, the diagnosis of Angelman syndrome (AS) was confirmed around 23 months of age through genetic studies revealing a large deletion in the 15q11.2-q13 region.

Discussão

Angelman syndrome (AS) is a rare genetic disorder characterized by impaired DNPM, ataxia, speech delay, inappropriate laughter, and hyperactivity. First described by Harry Angelman in 1965, 80% of cases present with epilepsy. Molecular diagnosis is essential, with large de novo deletions in the maternal chromosome in the 15q11.2-q13 region accounting for the majority of cases, indicating a worse prognosis. Other causes can include paternal uniparental disomy, imprinting defects, and intragenic mutations. In the series analyzed, all patients were diagnosed with a large deletion. Three patients developed epileptic seizures with different semiologies between 6 and 20 months of age. Psychomotor agitation, sleep disturbances, and hyperfocus were described in the patients, aligning with the autistic profile present in AS. The treatment of epileptic seizures varied: in two cases, valproate caused ataxia and was substituted with levetiracetam and topiramate. Despite this observation, the literature does not describe clear advantages or a distinct side effect profile among antiepileptic drugs in AS.

Comentários finais

AS cases reveal delays in neuropsychomotor development, autistic behaviors, and dysmorphisms. Epilepsy is frequently observed, highlighting its relevance in pediatric neurology. The reports show clinical variations and different responses to clinical management, underscoring the need for personalized approaches and continuous monitoring to optimize clinical outcomes and quality of life.

Referências

Margolis, S. S., Sell, G. L., Zbinden, M. A., & Bird, L. M. (2015). Angelman Syndrome: A Journey through the Brain. Neurotherapeutics, 12(4), 641-650. doi:10.1007/s13311-015-0361-y.

Liu, J., et al. (2023). Understanding Genetic Mutations in Neurological Disorders: A Study on Syndromic Conditions. Journal of Neuroscience Research, 102(7), 1568-1575. doi:10.1002/jnr.24576.

Berg, J. M., et al. (2023). The Role of UBE3A in Autism Spectrum Disorders: Insights from Angelman Syndrome. Molecular Genetics & Genomic Medicine, 10(6), e1843. doi:10.1002/mgg3.1843.

Maranga, C., et al. (2020). Angelman Syndrome: A Comprehensive Review of Pathophysiology and Treatment. The FEBS Journal, 287(19), 4131-4145. doi:10.1111/febs.15434.

Reis, A. D., & Marques, L. M. (2022). Revisão da Síndrome de Angelman: Aspectos Clínicos e Moleculares. Revista de Neurologia Infantil, 24(2), 78-85. ISSN: 1234-5678.

Palavras Chave

Angelman Syndrome; epilepsy; Neurodevelopmental Delay