(
) SNPs rs11240569 and rs823156 are associated with altered risk for Parkinson's disease (PD), predominantly in Asian populations, and rs708727 has been linked to Alzheimer's disease (AD). In this ...study, we have examined a potential association of the three aforementioned SNPs and of rs9438393, rs56152218, and rs61822602 (all three lying in the
promoter region) with PD in the Slovak population. Out of the six tested SNPs, we have identified only rs708727 as being associated with an increased risk for PD onset in Slovaks. The minor allele (A) in rs708727 is associated with PD in dominant and completely over-dominant genetic models (OR
= 1.36 (1.05-1.77),
= 0.02, and OR
= 1.34 (1.04-1.72),
= 0.02). Furthermore, the genotypic triplet GG
+ AG
+ CC
might be clinically relevant despite showing a medium (
≥ 0.5) size difference (
= 0.522) between the PD and the control populations. RandomForest modeling has identified the power of the tested SNPs for discriminating between PD-patients and the controls to be essentially zero. The identified association of rs708727 with PD in the Slovak population leads us to hypothesize that this
polymorphism, which is involved in the epigenetic regulation of the expression of the AD-linked gene
, is also involved in the pathoetiology of PD (or universally in neurodegeneration) through the same or similar mechanism as in AD.
Although there has been increasing recognition of the occurrence of non-epileptic involuntary movements in developmental and epileptic encephalopathies (DEEs), the spectrum of dystonic presentations ...associated with these conditions remains poorly described. We sought to expand the catalogue of dystonia-predominant phenotypes in monogenic DEEs, building on the recently introduced concept of an epilepsy-movement disorder spectrum.
Cases were identified from a whole-exome-sequenced cohort of 45 pediatric index patients with complex dystonia (67% sequenced as parent-child trios). Review of molecular findings in DEE-associated genes was performed. For five individuals with identified DEE-causing variants, detailed information about presenting phenotypic features and the natural history of disease was obtained.
De-novo pathogenic and likely pathogenic missense variants in GABRA1, GABBR2, GNAO1, and FOXG1 gave rise to infantile-onset persistent and paroxysmal dystonic manifestations, beginning in the limb or truncal musculature and progressing gradually to a generalized state. Coexisting, less prominent movement-disorder symptoms were observed and included myoclonic, ballistic, and stereotypic abnormal movements as well as choreoathetosis. Dystonia dominated over epileptic neurodevelopmental comorbidities in all four subjects and represented the primary indication for molecular genetic analysis. We also report the unusual case of an adult female patient with dystonia, tremor, and mild learning disability who was found to harbor a pathogenic frameshift variant in MECP2.
Dystonia can be a leading clinical manifestation in different DEEs. A monogenic basis of disease should be considered on the association of dystonia and developmental delay-epilepsy presentations, justifying a molecular screening for variants in DEE-associated genes.
•Epilepsy and non-epileptic abnormal movements can co-exist.•Five of 45 pediatric dystonia patients had variants in developmental and epileptic encephalopathy-related genes.•Mutant cases had complex dystonia but only minimal epileptic comorbidity.•Epilepsy and dystonia can form a phenotypical continuum within the category of neurodevelopmental disorders.•Epilepsy-related genes should be considered in genetic screening panels for dystonia.
Background. An increased prevalence of Parkinson’s disease (PD) disease has been previously reported in subjects with Fabry disease (FD) carrying alpha-galactosidase (GLA) mutations and their ...first-line relatives. Moreover, decreased alpha-galactosidase A (AGLA) enzymatic activity has been reported among cases with PD compared to controls. Objective. The aim of our study was to determine the prevalence of FD among patients with PD. Methods. We recruited 236 consecutive patients with PD from February 2018 to December 2020. Clinical and sociodemographic data, including the MDS-UPDRS-III scores and HY stage (the Hoehn and Yahr scale), were collected, and in-depth phenotyping was performed in subjects with identified GLA variants. A multistep approach, including standard determination of AGLA activity and LysoGb3 in males, and next-generation based GLA sequencing in all females and males with abnormal AGLA levels was performed in a routine diagnostic setting. Results. The mean age of our patients was 68.9 ± 8.9 years, 130 were men (55.1%), and the mean disease duration was 7.77 ± 5.35 years. Among 130 men, AGLA levels were low in 20 patients (15%), and subsequent Lyso-Gb3 testing showed values within the reference range for all tested subjects. In 126 subsequently genetically tested patients, four heterozygous p.(Asp313Tyr) GLA variants (3.2%, MAF 0.016) were identified; all were females. None of the 4 GLA variant carriers identified had any clinical manifestation suggestive of FD. Conclusions. The results of this study suggest a possible relationship between FD and PD in a small proportion of cases. Nevertheless, the GLA variant found in our cohort is classified as a variant of unknown significance. Therefore, its pathogenic causative role in the context of PD needs further elucidation, and these findings should be interpreted with caution.
Background
The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS‐UPDRS) is a newly developed tool to assess Parkinson's disease (PD). Changes in scores on the scale over the ...course of PD, including increasing disease duration and Hoehn and Yahr (HY) stages, have not been described. The objectives of this study were to analyze MDS‐UPDRS scores on Parts I through IV and their differences based on HY stage and disease duration in a large cohort of patients with PD.
Methods
For this cross‐sectional study, demographic data and MDS‐UPDRS scores were collected, including HY stage. Subscores on MDS‐UPDRS Parts I through IV were analyzed using 1‐way analyses of variance for each HY stage and in 5‐year increments of disease duration. Part III (motor assessment) scores were analyzed separately for on and off states.
Results
The mean age of the 3206 patients was 65.8 ± 10.6 years, 53.3% were men, the mean disease duration was 11.5 ± 4.6 years, and the median HY stage was 2 (range, 0–5); 2156 patients were examined in an on state and 987 were examined in an off state. Scores for all MDS‐UPDRS parts increased significantly through HY stages 1 through 5, with an average increase of 3.8, 7.7, 14.6, and 2.0 points consecutively for parts I through IV, respectively. For the 5‐year increments of disease duration, MDS‐UPDRS subscores increased by an average of 1.6, 3.3, 4.2, and 1.4 points consecutively for parts I through IV, respectively. This increase was significant only during the first 15 years of disease for all 4 parts, including part III scores evaluated in both on and off states.
Conclusions
MDS‐UPDRS scores for all 4 parts increase significantly with every HY stage and also with 5‐year increments of disease duration in the first 15 years of the disease.
After successful clinimetric testing of the Unified Dyskinesia Rating Scale (UDysRS), a program for translation and validation of non-English versions of the UDysRS was initiated. The aim of this ...study was to validate and confirm the factor structure of the Slovak translation of the UDysRS. We examined 251 patients with Parkinson’s disease and dyskinesia using the Slovak version of the UDysRS. The average age of our sample was 65.2 ± 9.2 years and average disease duration was 10.9 ± 5.0 years. Slovak data were compared using confirmatory factor analysis with the Spanish data. To be designated as the official Slovak UDysRS translation, the comparative fit index (CFI) had to be ≥0.90 relative to the Spanish language version. Exploratory factor analysis was performed to explore the underlying factor structure without the constraint of a prespecified factor structure. For all four parts of the Slovak UDysRS, the CFI, in comparison with the Spanish language factor structure, was ≥0.98. Isolated differences in the factor structure of the Slovak UDysRS were identified by exploratory factor analysis compared with the Spanish version. The Slovak version of the UDysRS was designated as an official non-English translation and can be downloaded from the website of the International Parkinson and Movement Disorder Society.
Abstract The Movement Disorder Society–Unified Parkinson's Disease Rating Scale (MDS–UPDRS) is a newly developed comprehensive tool to assess Parkinson's disease (PD), which covers a wider range of ...non-motor PD manifestations than the original UPDRS scale. The aim of this study was to assess the relationship between the MDS–UPDRS and Quality of Life (QoL) and to analyze the relationship between individual MDS–UPDRS non-motor items and QoL. A total of 291 PD patients were examined in a multicenter Slovak study. Patients were assessed by the MDS–UPDRS, HY scale and PDQ39. Data were analyzed using the multiple regression analyses. The mean participant age was 68.0 ± 9.0 years, 53.5% were men, mean disease duration was 8.3 ± 5.3 years and mean HY was 2.7 ± 1.0. In a multiple regression analysis model the PDQ39 summary index was related to MDS–UPDRS parts II, I and IV respectively, but not to part III. Individual MDS–UPDRS non-motor items related to the PDQ39 summary index in the summary group and in the non-fluctuating patients subgroup were pain, fatigue and features of dopamine dysregulation syndrome (DDS). In the fluctuating PD patient subgroup, PDQ39 was related to pain and Depressed mood items. Other MDS–UPDRS non-motor items e.g. Anxious mood, Apathy, Cognitive impairment, Hallucinations and psychosis, Sleep problems, Daytime sleepiness and Urinary problems were related to some PDQ39 domains. The overall burden of NMS in PD is more important in terms of QoL than motor symptoms. Individual MDS–UPDRS non-motor items related to worse QoL are especially pain and other sensations, fatigue and features of DDS.
•Two subjects with novel TCF20 variants in whom dystonia was a leading phenotype.•Expand the spectrum of TCF20 neurodevelopmental disease to a dystonia-prominent.•To increase awareness of movement ...disorders contributing to developmental disorders.
Central European Group on Genetics of Movement Disorders Ostrozovicova, Miriam; Dusek, Petr; Grofik, Milan ...
European journal of neurology,
April 2024, 2024-Apr, 2024-04-00, 20240401, Letnik:
31, Številka:
4
Journal Article
Recenzirano
Odprti dostop
APPENDIX MEMBERS OF THE CENTRAL EUROPEAN GROUP ON GENETICS OF MOVEMENT DISORDERS (CEGEMOD) MEMBERS BY COUNTRY Czech Republic Dusek Petr, Department of Neurology and Centre of Clinical Neuroscience, ...First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. petr.dusek@vfn.cz Holly Petr, Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. petr.holly@vfn.cz Jech Robert, Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. jech@cesnet.cz Ruzicka Evzen, Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. evzen.ruzicka@lf1.cuni.cz Serranova Tereza, Department of Neurology and Centre of Clinical Neuroscience, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic. tereza.serranova@lf1.cuni.cz Zarubova Katerina, Department of Neurology, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Prague, Czech Republic. katzar@centrum.cz Hungary Klivenyi Peter, Department of Neurology, University of Szeged, Szeged, Hungary. klivenyi.peter@med.u-szeged.hu University of Pecs, Medical School, Department of Neurology and HUN-REN–PTE Clinical Neuroscience MR Research Group. kovacsnorbert06@gmail.com Pinter David, University of Pecs, Medical School, Department of Neurology and HUN-REN–PTE Clinical Neuroscience MR Research Group. david_pinter@outlook.com Tamas Gertrud, Department of Neurology, Semmelweis University, Budapest, Hungary. tamas.gertrud@med.semmelweis-univ.hu Poland Department of Neurology Silesian Centre of Neurology, Katowice, Poland. kasia.smilowska@gmail.com Slovak Republic Grofik Milan, Department of Neurology, Commenius University and University Hospital Martin, Martin, Slovak Republic. milangrofik@gmail.com Han Vladimir, Department of Neurology, Safarik University and L. Pasteur University Hospital Kosice, Slovak Republic. vladimir.han@gmail.com Kulcsarova Kristina, Department of Neurology, Safarik University and L. Pasteur University Hospital Kosice, Slovak Republic. kristina.kulcsarova@upjs.sk Kurca Egon, Department of Neurology, Commenius University and University Hospital Martin, Martin, Slovak Republic. egonkurca@gmail.com Lackova Alexandra, Department of Neurology, Safarik University and L. Pasteur University Hospital Kosice, Slovak Republic. alexandra.mosejova@gmail.com Magocova Veronika, Department of Neurology, Safarik University and L. Pasteur University Hospital Kosice, Slovak Republic. veronikamagocova.a@gmail.com Necpal Jan, Department of Neurology, Zvolen Hospital, Zvolen, Slovak Republic. necpal.neuro@gmail.com Ostrozovicova Miriam, Department of Neurology, Safarik University and L. Pasteur University Hospital Kosice, Slovak Republic. miriam.ostrozovicova@gmail.com; m.ostrozovicova@ucl.ac.uk Skorvanek Matej, Department of Neurology, Safarik University and L. Pasteur University Hospital Kosice, Slovak Republic. mskorvanek@gmail.com Straka Igor, Second Department of Neurology, Comenius University in Bratislava Faculty of Medicine, University Hospital Bratislava, Bratislava, Slovak Republic. straka0105@gmail.com Svorenova Tatiana, Department of Neurology, Safarik University and L. Pasteur University Hospital Kosice, Slovak Republic. talorinc@gmail.com Valkovic Peter, Second Department of Neurology, Comenius University in Bratislava Faculty of Medicine, University Hospital Bratislava, Bratislava, Slovak Republic; Institute of Normal and Pathological Physiology, Centre of Experimental Medicine, Slovak Academy of Sciences, Bratislava, Slovak Republic peter.valkovic@gmail.com United Kingdom Houlden Henry, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK. h.houlden@ucl.ac.uk Rizig Mie, Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, London, UK. m.rizig@ucl.ac.uk Kulcsarova K, Ventosa JR, Feketeova E, et al. Comparison in detection of prodromal Parkinson's disease patients using original and updated MDS research criteria in two independent cohorts. LRRK2 mutations in Parkinson's disease patients from Central Europe: a case−control study.
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