https://repositorio.fleni.org.ar/xmlui/handle/123456789/20 2026-10-01T20:39:33Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1599 Essential genetic testing in movement disorders - results from a Delphi study Carvalho, Vanessa; Correia Guedes, Leonor; Gatto, Emilia M.; Rodriguez-Violante, Mayela; Klein, Christine; Rodriguez-Porcel, Federico; Morgante, Francesca; Rossi, Malco Damián; Miranda, Marcelo; Ganos, Christos; Riboldi, Giulietta M.; Cesarini, Martin; Darling, Alejandra; Skorvanek, Matej; Van de Warrenburg, Bart; Shalash, Ali; Cossu, Giovanni; Friedman, Jennifer; Albanese, Alberto; Cardozo, Adriana Background: While genetic testing in Movement Disorders (MD) has expanded enormously, access to genetic testing and genetic counseling remains asymmetric at the global scale. Guidance on efficient testing strategies for clinicians, governments and stakeholders is crucial. Objectives: Establish a list of genetic movement disorders considered essential as determined by a group of MD experts. Methods: All genes associated with MD were searched using the OMIM and MDS Gene database. We collected all additional tests available at 4 different laboratories from the EuroGentest database. The results were compiled in 6 questionnaires. A genetic test was considered essential if molecular testing had a direct impact in the management of the patient, including treatment of the disease or its comorbidities, or genetic counseling of the patient and family members. Two Delphi rounds were conducted asking MD experts which specific tests they considered essential in an adult MD clinic. Results: Fifty-nine disorders were considered essential to genetically identify by the MD experts. This included 25 genes associated with ataxia, 15 with parkinsonism, 14 with dystonia, eight with chorea, five with paroxysmal disorders, four with myoclonus, four with hereditary spastic paraparesis, and one with tremor. Sixteen disorders reached 100% consensus among experts: Huntington's disease, PxMD-PPRT2, Wilson's disease, DYT-SGCE, DYT-THAP1, DYT-TOR1A, DYT/PARK-GCH1, Fragile-X Tremor-ataxia syndrome, PARK-GBA, PARK-LRRK2, PARK-PINK1, PARK-PRKN, PARK-SNCA, Cerebrotendinous Xanthomatosis, Ataxia-Telangiectasia, and Niemann-Pick disease type C. Conclusion: This study provides a list of genetic MD that should be molecularly tested in adult centers with a compatible phenotype according to a group of MD experts. 2026-07-01T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1590 Unravelling the Global Tapestry of Genetic Ataxias: Epidemiology and Genetic Testing Approaches Rossi, Malco Damián; Stephen, Christopher D.; Damásio, Joana; Pedroso, José Luiz; Kuo, Sheng-Han; Lin, Chi-Ying R.; Ojo, Oluwadamilola; El-Jaafary, Shaimaa; Lee, Woong-Woo; Madoev, Harutyun; Barsottini, Orlando G.; Srivastava, Achal Kumar; Klein, Christine; Van de Warrenburg, Bart The landscape of genetic ataxias is influenced by migration, population genetics, consanguinity, and founder effects, resulting in significant regional variation. Within the expanding domain of genetic ataxias, knowledge of regional epidemiology is scarce, particularly outside of North America and Europe. Understanding the epidemiology of genetic ataxias, together with deep phenotyping and knowledge of the appropriate ancillary studies, is crucial for the development and deployment of diagnostic testing strategies. This review offers a comprehensive, data-driven overview of 2932 articles with regional epidemiological estimates and the occurrence and prevalence of 548 genes associated with ataxia across 122 countries. Regional differences in epidemiology and phenotypic spectra are highlighted, driving an approach that incorporates complementary diagnostic test results and how these may inform cost-effective, region-specific genetic testing. All data are also publicly available as an online database, the MDSGene Global Genetic Ataxia Resource, accessible at https://www.mdsgene.org/ataxia.html. A phenotype-guided, tailored, and sequential testing approach is proposed, based on regional prevalence, to assist clinicians worldwide in diagnosing individuals with presumed genetic ataxia, of which at least 45 causes are treatable. This approach is particularly important in underserved regions, but also in developed countries where health systems limit access to genetic testing, improving the cost-effectiveness and feasibility of genetic testing in these areas. Future screening studies in high-income settings should adopt a more comprehensive approach, integrating broader genetic testing that covers the full range of genetic ataxias. Capacity building for genetic screening in underserved regions, particularly in Africa, South America, and the Middle East, should be prioritized. © 2025 International Parkinson and Movement Disorder Society. 2025-07-18T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1564 Systematic review of movement disorders mislabeled as functional: when incongruence misleads Marín-Medina, Daniel S.; Miño Zambrano, Joselyn; Espay, Alberto J.; Merello, Marcelo Background: Misdiagnosis of functional movement disorders (FMD) remains a concern for clinicians. We sought to review the phenomenology and clinical features associated with FMD misdiagnosis. Methods: We conducted a systematic review of case reports, case series, and observational studies of adults diagnosed with FMD and subsequently reclassified as having another neurological or medical condition. PubMed was searched from inception to September 13, 2025, focusing on reported features of inconsistency, incongruence with known diseases, and low-validity features. Isolated (iMD) and mixed (mMD) movement disorders were analyzed separately. Results: Forty-two included studies comprised 150 patients, of which 73 cases underwent detailed analysis. Gait disturbance (35%) and dystonia (27.5%) were the most common iMD phenomenologies (n = 40), while jerks and rigidity (24%) were the most common mMD phenomenology (n = 33). Incongruence with known diseases (50.7%), psychological factors (34.2%), and symptom variability (31.5%) were the main factors associated with misdiagnosis. Application of incongruence alone was associated with the highest rate of FMD misdiagnosis, similar to that of applying neither incongruence nor inconsistency (49% in both cases). Conversely, reliance on inconsistency alone was least associated with an FMD misdiagnosis (13.7%). Misdiagnoses of iMD were more likely in the absence of documented inconsistency (OR 3.94, 95% CI 1.32-12.82). Conclusions: FMD misdiagnoses, particularly of gait disorders and dystonia, were most commonly associated with the application of incongruence as diagnostic criterion. The lowest rate of FMD misdiagnosis was associated with ascertaining at least two positive neurological signs of inconsistency. 2026-04-08T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1556 Early motor response to dopamine replacement therapy in Parkinson's disease patients carrying GBA variants Rossi, Malco Damián; Castillo Torres, Sergio Andrés; Merello, Marcelo Background: Mutations in the glucocerebrosidase (GBA) gene represent the most common genetic risk factor for Parkinson's Disease (PD) and are associated with a more aggressive motor phenotype at late stages. However, the motor response at early stages of disease remains understudied. Methods: Retrospective study of PD patients that underwent next-generation sequencing panel tests for PD-related genes. We extracted demographic data and the MDS-UPDRS III response to an acute levodopa challenge (LDC), the best ON score, and the levodopa equivalent daily dose (LEDD) during the first six months after the LDC and initiation of DRT. We compared the response of GBA-PD patients to that of patients without pathogenic variants or rearrangements in other PD related genes (sporadic PD). Results: 13 GBA-PD and 48 sporadic PD patients were identified. Baseline MDS-UPDRS III score (24.6 ± 9.6 vs. 21.8 ± 9.3. p = 0.4), response to LDC (39.2% ± 7.9% vs. 32.7% ± 13.4%; p = 0.1), best ON score (36.9% ± 39.5% vs. 41.6% ± 20.8%; p = 0.6) and LEDD (188 mg ± 100 mg vs. 261.8 mg ± 164.8 mg; p = 0.2) during the first six months after initiation of DRT were not different between GBA-PD and sporadic PD patients. Conclusions: At early disease stages of GBA-PD, the motor response to acute levodopa challenge test and the initial response to DRT are similar to that of patients with sporadic PD. Although limited by small sample size, these preliminary findings should be confirmed by future prospective larger studies. 2022-09-15T00:00:00Z