Dados do Trabalho

Título

NEURODEVELOPMENT AND MOVEMENT DISORDERS RELATED TO GNAO1: REPORT OF TWO CASES WITH DIFFERENT OUTCOMES

Apresentação dos casos

We report two neurological conditions due to pathogenic variants in the GNAO1 gene with different ages and outcomes. The first patient had a previous diagnosis of cerebral palsy attributed to perinatal hypoxia, although he had no history of gestational or delivery complications. He had a delay in developmental milestones and was up to 9 years old; the patient presented with a chronic non-progressive encephalopathy and was unable to walk independently. From that age onwards, involuntary movements began, and extensive investigation ruled out auto-immune encephalitis. At 17 years of age, the patient was hospitalized with dyskinetic status. Brain MRI was normal. The turning point in his diagnosis came with the request for a genetic panel, which identified a pathogenic variant in the GNAO1 gene. Even with treatment attempts, he died. The second patient, now five years and seven months old, was noted to have hypotonia and movement disorders at four months of age, with no other findings. A genetic panel was requested, and a pathogenic variant in the GNAO1 gene was identified, underscoring the importance of this diagnostic tool. With the optimization of the pharmacological treatment of movement disorder, his dyskinetic movements remain stable and improving.

Discussão

Disorders related to the GNAO1 gene are related to a broad spectrum of neurological changes, generally associated with abnormal movements and epilepsy, in addition to developmental delay and intellectual disability. Autosomal dominant inheritance, but most cases are de novopathogenic variants. In general, phenotypes with early-onset epilepsy present more severe conditions with developmental epileptic encephalopathy. Hyperkinetic movement disorders mainly include dystonias and choreoathetosis.

Comentários finais

It has not yet been possible to define whether there is a chance of average life expectancy in patients but advances in therapies have enabled important survival into adulthood.

Referências

Briere L, Thiel M, Sweetser DA, Koy A, Axeen E. GNAO1-Related Disorder. 2023 Nov 9. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2024. PMID: 37956232.
Novelli M, Galosi S, Zorzi G, Martinelli S, Capuano A, Nardecchia F, Granata T, Pollini L, Di Rocco M, Marras CE, Nardocci N, Leuzzi V. GNAO1-related movement disorder: An update on phenomenology, clinical course, and response to treatments. Parkinsonism Relat Disord. 2023 Jun;111:105405. doi: 10.1016/j.parkreldis.2023.105405. Epub 2023 Apr 29. PMID: 37142469.

Palavras Chave

Developmental and epileptic encephalopathy; GNAO1; movement disorders