Dados do Trabalho

Título

ETIOLOGICAL INVESTIGATION OF NEURODEVELOPMENTAL DISORDERS AND EARLY-ONSET MOVEMENT DISORDERS IN APAES

Introdução

Neurodevelopmental Disorders (ND) and early-onset Movement Disorders (MD) in childhood are common conditions that affect multiple areas of development, such as cognition and motor skills. Some of these disorders are progressive but potentially treatable. The clinical variability makes etiological diagnosis a challenge, and the resources for investigation in various regions of the country are limited and/or scarce.

Objetivo

Investigate possible genetic causes of ND and MD through Next-Generation Sequencing in a selected profile of patients from APAEs (Association of Parents and Friends of Exceptional Children) within Brazilian territory.

Método

Application of Next-Generation Sequencing using a panel of 91 genes already associated with ND and MD in saliva samples (collected via oral swab) from previously selected patients, without age restriction, with clinical criteria compatible with early-onset ND and/or MD.

Resultados

The study involves 116 APAEs distributed across all regions of the country. Samples from 286 patients from 11 APAEs have been analyzed so far. Seven pathogenic/probably pathogenic variants were found in genes commonly associated with intellectual disability and epilepsy (FOXG1, MECP2, PRRT2, GRIN2B, SLC2A1, SLC6A1, TBL1XR1). In addition to the variants in specific genes, four pathogenic CNVs (copy number variants) were identified: (del5p15.33, del5p13.3p14.1, del9q34.11, del16p11.2). These deletions include many genes and explain the clinical condition of the patients. In 10 patients, variants of uncertain clinical significance were identified, requiring further testing to determine their pathogenicity.

Conclusão

ND and MD present with variable and extensive clinical manifestations, which complicates etiological diagnosis and the implementation of potential specific treatments. Providing diagnostic tools that are cost-free and non-invasive enables intervention for potentially treatable cases, reduces comorbidities and complications, and facilitates genetic counseling. The implementation of genetic testing in APAEs allows access to diagnosis for patients throughout Brazil, including those in remote areas outside major urban centers.

Referências

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Palavras Chave

Distúrbios do neurodesenvolvimento; Transtornos do movimento; Sequenciamento de nova geração