Banca de DEFESA: Agostinho de Alencar Guerra

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
STUDENT : Agostinho de Alencar Guerra
DATE: 22/12/2023
TIME: 14:00
LOCAL: Online - Plataforma TEAMS
TITLE:

Levodopa-responsive dystonia due to mutations in the GCH1/TH genes - cohort of patients treated at the Sarah Network of Rehabilitation Hospital

KEY WORDS:

GCH1, TH, DRD, Segawa disease, Dystonia, Dystonic disorders

PAGES: 71
BIG AREA: Ciências da Saúde
AREA: Medicina
SUMMARY:

Introduction: Dopa-responsive dystonia (DRD), also known as Segawa Disease, was first described in 1971. Variants in the GCH1 gene inherited in an autosomal dominant pattern are the most common cause of DRD. In Latin America, there have been few published studies on DRD. This study aims to describe the genetic and clinical profile of a cohort of patients from a rehabilitation hospital network in Brazil. Materials and Methods: This is a descriptive study of a group of 22 patients treated in our hospital network. For each patient who underwent genetic testing by next-generation sequencing (NGS), a retrospective analysis of clinical features and evolution was performed for a phenotype-genotype correlation. Results: Variants associated with DRD were detected in 17 out of the 22 patients (77%). Among these 17 patients, variants in the GCH1 gene were detected in 16 (94%), while only one patient had a variant in the TH gene (5%). Among the 16 patients with variants in the GCH1 gene, 10 patients had variants classified as pathogenic, 5 patients had variants likely to be pathogenic, and 1 patient had a variant of unknown significance (VUS). The variant of the TH gene was classified as VUS. Five patients had no variants detected. The clinical findings were highly similar to other studies, such as an average age of onset around 8 years old, a predominance of females, a good response to low doses of levodopa, and a significant diagnostic delay. However, complex phenotypes were identified in this large cohort of cases, including a substantial number of unrelated individuals without a family history. Another notable point was the frequency of levodopa-induced motor dyskinesias. Additionally, patients experienced behavioral symptoms severe enough to require medication for psychiatric disorders. Conclusion: This descriptive study of a group of 22 patients treated in a hospital network showed classical phenotypic findings previously described in other studies, along with uncommon characteristics such as levodopa-induced dyskinesias, frequent behavioral findings, medication use for psychiatric disorders, and complex phenotypes. These findings highlight the need for further research regarding the GCH1 and TH genes:

COMMITTEE MEMBERS:
Interno - 1156673 - FELIPE VON GLEHN SILVA
Externa à Instituição - CLARICE LISTIK - USP
Externa à Instituição - INGRID FABER DE VASCONCELOS - HUB
Externo à Instituição - PEDRO RENATO DE PAULA BRANDÃO - SÍRIO