BACKGROUND:Functional neurological movement disorders are common and disabling. Little is known about their coexistence with other non-functional movement disorders and their impact on the general disease burden. OBJECTIVES:Investigating frequency and characteristics of functional movement disorders in GCH1-positive dopa-responsive dystonia patients. METHODS:Twenty-one patients underwent a detailed clinical motor examination and completed self-questionnaires evaluating non-motor characteristics. RESULTS:Seven patients (33 %) had comorbid functional movement symptoms, including functional gait disorders (n = 7), balance disturbances (n = 7), and weakness (n = 5), dominating the clinical phenotype and resulting in disability with immobilization. None of them was previously diagnosed with or treated for the functional symptoms. Functional movement symptoms appeared suddenly (on average 18 years after the first dopa-responsive dystonia symptoms) and were unresponsive to L-Dopa. These patients showed significantly higher disability and received unnecessary treatments. CONCLUSION:Functional neurological movement disorders are common in patients with dopa-responsive dystonia and impact the clinical picture and the degree of disability. Diagnosing both disorders in an individual patient has substantial therapeutical implications because increases in L-Dopa dosages to treat functional symptoms should be avoided, and physiotherapy should relocate attention away from the affected body region so that movements in the affected body part can be executed without external control to facilitates automatic movements. Physiotherapy should be complemented by psychoeducation and psychotherapeutic approaches.

OBJECTIVE:Dystonia is one of the most prevalent movement disorders, characterized by significant clinical and etiological heterogeneity. Despite considerable heritability (~25%), the etiology in most patients remains elusive. Moreover, understanding correlations between clinical manifestations and genetic variants has become increasingly complex. METHODS:Exome sequencing was conducted on 1924 genetically unsolved, mainly late-onset isolated dystonia patients, recruited primarily from two dystonia registries (DysTract and the Dystonia Coalition). Rare variants in genes previously linked to dystonia (n = 406) were examined, confirmed via Sanger sequencing, and analyzed for segregation when possible. RESULTS:We identified 137 distinct likely pathogenic/pathogenic variants (according to ACMG criteria) across 51 genes in 163/1924 patients, including 153/1895 index patients (diagnostic yield 8.1%). The strongest predictors of a genetic diagnosis were generalized dystonia (28.6% yield) and age at onset (20.4% yield in patients with onset < 30 years). Notably, 56.2% of these variants were novel, with recurrent variants in EIF2AK2, VPS16, KCNMA1, and SLC2A1. Additionally, 321 index patients (16.9%) harbored variants of uncertain significance in 102 genes. The most frequently implicated genes included VPS16, THAP1, GCH1, SGCE, GNAL, and KMT2B. Presumably pathogenic variants in less well-established dystonia genes were also found, including KCNMA1, KIF1A, and ZMYND11. At least six variants (in ADCY5, GNB1, IR2BPL, KCNN2, KMT2B, and VPS16) occurred de novo, supporting pathogenicity. INTERPRETATION:This study provides valuable insights into the genetic landscape of dystonia, underscores the utility of exome sequencing for diagnosis, substantiates several candidate genes, and expands the phenotypic spectrum of some genes to include prominent, sometimes isolated dystonia.

Individuals with ultrarare disorders pose a structural challenge for healthcare systems since expert clinical knowledge is required to establish diagnoses. In TRANSLATE NAMSE, a 3-year prospective study, we evaluated a novel diagnostic concept based on multidisciplinary expertise in Germany. Here we present the systematic investigation of the phenotypic and molecular genetic data of 1,577 patients who had undergone exome sequencing and were partially analyzed with next-generation phenotyping approaches. Molecular genetic diagnoses were established in 32% of the patients totaling 370 distinct molecular genetic causes, most with prevalence below 1:50,000. During the diagnostic process, 34 novel and 23 candidate genotype–phenotype associations were identified, mainly in individuals with neurodevelopmental disorders. Sequencing data of the subcohort that consented to computer-assisted analysis of their facial images with GestaltMatcher could be prioritized more efficiently compared with approaches based solely on clinical features and molecular scores. Our study demonstrates the synergy of using next-generation sequencing and phenotyping for diagnosing ultrarare diseases in routine healthcare and discovering novel etiologies by multidisciplinary teams.

Background Cervical dystonia (CD) is a movement disorder that is characterized by involuntary muscle contractions causing abnormal head postures. Current assessments rely primarily on infrequent clinical evaluations and subjective patient-reported outcomes (about every 3 to 4 months), limiting detailed understanding of symptom progression between treatments. Objective Improved understanding of symptom progression would enhance personalized treatment with Botulinum toxin A therapy. For this purpose, we introduce Move2Screen, a smartphone application designed for frequent home-based, asynchronous video monitoring of symptom progression for CD patients. We evaluate the usability and adherence of Move2Screen. Methods Adherence was assessed in a longitudinal home-based observational study involving eight from initially 11 patients with CD who continued participation after the initial on-site acquisition. Usability was measured using the German mHealth App Usability Questionnaire (G-MAUQ) after the two-week mark, which evaluates ease-of-use, interface satisfaction, and usefulness. Adherence was analyzed by tracking the frequency and timing of recorded videos. Results The app showed good overall usability scores on the G-MAUQ and a high adherence rate, with participants completing 74% of the intended video recordings. However, usability evaluations highlighted some challenges in perceived usefulness and minor technical issues reported by users. Conclusion The Move2Screen app demonstrates promising usability and adherence for home-based symptom monitoring in CD. However, addressing technical limitations, expanding participant cohorts, and integrating clinical decision support are essential next steps. These developments may enhance individualized care by enabling more informed therapeutic adjustments and improving long-term disease management.

Background: Cervical dystonia (CD) is the most common form of focal dystonia encountered in the clinic. Approximately one-third of CD patients have co-existing tremor in the head and hands. Assessment of tremor as regular or irregular in context of its oscillation trajectory, frequency, and amplitude is a major clinical challenge and can confound the diagnosis of CD. The misdiagnosis may lead to therapeutic failures, poor quality of life, and poor utilization of medical and financial resources.Methods: We analyzed the largest cohort of CD patients (n = 3117) available to date, collected from 37 movement disorder centers in North America, Europe, and Asia. We used machine learning to determine what clinical features from clinician reports predicted the presence of tremor as well as its regular or irregular appearance.Results: Out of 3,117 CD patients, 1,367 had neck tremor. The neck tremor was interpreted as irregular in 1,022, regular in 345, and mixed (both irregular and regular) in 442. A feature importance analysis determined that greater severity of CD, longer disease duration, and older age, in descending order, predicted the presence of neck tremor. The probability of neck tremor was reduced if the dystonia affected other body parts in addition to the neck. We also found a significantly heightened risk for developing neck tremor in women. An additional feature importance analysis indicated that increased severity of dystonia affecting other body parts, severity of CD, and prolonged disease duration was associated with a lower likelihood of regular neck tremor while increased age predicted a higher likelihood.Conclusion: Machine learning recognized the most relevant clinical features that can predict concurrent neck tremor and its irregularity in a large multi-center dystonia cohort. These results may facilitate a more accurate description of neck tremor and improved care path in CD.

Functional movement disorders are amongst the most common and disabling neurological conditions, placing a significant burden on the healthcare system. Despite the frequency and importance of functional movement disorders, our understanding of the underlying pathophysiology is limited, hindering the development of causal treatment options. Traditionally, functional movement disorders were considered as a psychiatric condition, associated with involuntary movements triggered by psychological stressors. Recent neurophysiological studies have unveiled cognitive alterations in affected individuals, suggesting that functional movement disorders might be better characterized by overarching neural principles governing cognitive functions. For instance, recent research has shown that the retrieval of stimulus-response bindings is altered in patients with functional movement disorders. Building upon these recent findings, our study delves into whether the initial integration of stimulus and response information is also disrupted in patients with functional movement disorders. To accomplish this, we reanalysed previously collected EEG data using refined analysis methods that provide insights into oscillatory activity and functional neuroanatomy associated with the integration of stimulus-response bindings. Our results demonstrate that post-movement beta synchronization (i) predicts behavioural stimulus-response binding and (ii) is significantly increased in patients with functional movement disorders compared to healthy controls. Utilizing beamformer analysis, we localized the difference effect to a cluster centred around the left supplementary motor area and the correlation effect to the right supplementary motor area. Extending beyond recent research that focused on the retrieval of stimulus-response bindings, our present findings reveal that the integration of stimulus and response information is already impaired in patients with functional movement disorders. These results uncover a phenomenon of hyperbinding between perception and action, which may represent a fundamental mechanism contributing to the movement impairments in patients with functional movement disorders. Past & ouml;tter et al. reveal altered integration of stimulus and response information in patients with functional movement disorders using EEG data analysis. Compared to healthy controls they find heightened post-movement beta synchronization predicting increased stimulus-response binding, particularly in the supplementary motor area confirming altered perception-action integration in these patients.See Marthe Meppelink, M. de Jong and Beudel (https://doi.org/10.1093/braincomms/fcae339) for a scientific commentary on this article. Graphical Abstract

Introduction Idiopathic blepharospasm is a clinically heterogeneous form of focal dystonia, also associated with psychiatric symptoms. The identification of the most relevant sets of motor and psychiatric manifestations may help better understand the specific phenomenology of the condition and delineate blepharospasm subtypes more accurately. Methods Patients with idiopathic blepharospasm were from the Dystonia Coalition project. Factor analysis of several motor and psychiatric scales was performed to identify the relevant determinants of blepharospasm severity. The selected items were then used in a data-driven cluster analysis to subtype blepharospasm individuals. Results Factor analysis reduced the many variables in the motor and psychiatric scales to 13 variables distributed in four factors. When the four sets were used as clustering variables, three blepharospasm clusters were identified: cluster 1 was characterized by low levels of motor and psychiatric factors; cluster 2 showed high levels of both motor and psychiatric factors; and cluster 3 showed high levels of psychiatric factors (similar to cluster 2) but low level of motor factors (similar to that of cluster 1). Conclusions Factor analysis enabled the identification of key motor and psychiatric determinants of blepharospasm severity. The derived factor sets provide a streamlined tool for predicting and measuring these dimensions. This approach also facilitated more precise cluster analysis and improved recognition of clinical subtypes.

Background In 2017, the German Academy for Rare Neurological Diseases (Deutsche Akademie für Seltene Neurologische Erkrankungen; DASNE) was founded to pave the way for an optimized personalized management of patients with rare neurological diseases (RND) in all age groups. Since then a dynamic national network for rare neurological disorders has been established comprising renowned experts in neurology, pediatric neurology, (neuro-) genetics and neuroradiology. DASNE has successfully implemented case presentations and multidisciplinary discussions both at yearly symposia and monthly virtual case conferences, as well as further educational activities covering a broad spectrum of interdisciplinary expertise associated with RND. Here, we present recommendation statements for optimized personalized management of patients with RND, which have been developed and reviewed in a structured Delphi process by a group of experts. Methods An interdisciplinary group of 37 RND experts comprising DASNE experts, patient representatives, as well as healthcare professionals and managers was involved in the Delphi process. First, an online collection was performed of topics considered relevant for optimal patient care by the expert group. Second, a two-step Delphi process was carried out to rank the importance of the selected topics. Small interdisciplinary working groups then drafted recommendations. In two consensus meetings and one online review round these recommendations were finally consented. Results 38 statements were consented and grouped into 11 topics: health care structure, core neurological expertise and core mission, interdisciplinary team composition, diagnostics, continuous care and therapy development, case conferences, exchange / cooperation between Centers for Rare Diseases and other healthcare partners, patient advocacy group, databases, translation and health policy. Conclusions This German interdisciplinary Delphi expert panel developed consented recommendations for optimal care of patients with RND in a structured Delphi process. These represent a basis for further developments and adjustments in the health care system to improve care for patients with RND and their families.

BACKGROUND:Dystonia is a hyperkinetic movement disorder that results in twisting, cramps and tremors due to sustained or intermittent muscle contractions. Cervical dystonia is the most common form of dystonia, in which the head, neck and/or shoulder areas are affected. In addition to these motor symptoms, pain and psychiatric symptoms are frequent in (cervical) dystonia. OBJECTIVE:Description of the incidence and evaluation of pain in cervical dystonia, summary and discussion of treatment options and effects. MATERIAL AND METHODS:In this review article the results in the scientific literature on pain in dystonia are summarized and discussed. RESULTS:Compared to other forms of dystonia, pain occurs most frequently in patients with cervical dystonia. A large proportion of patients with cervical dystonia suffer from pain, which contributes most to impairment of the patient. The motor symptoms of dystonia are usually treated with botulinum toxin injections. These have a muscle relaxing effect and also relieve pain. The study situation on the occurrence and treatment of pain in other forms of dystonia is so far very limited. Pain can dominate the clinical picture in patients with cervical dystonia. Evaluation of pain in cervical dystonia can be performed using standardized questionnaires. CONCLUSION:It is important to ask patients with cervical dystonia about pain and to consider it in treatment planning and evaluation. Vice versa, if pain is present the possibility of a causative dystonia should also be considered. For pain assessment there are some newly developed questionnaires to assess pain in a standardized way in patients with dystonia. Further research is needed to better understand the pathomechanisms of pain in dystonia.

Background:Despite considerableheritability, previous smaller genome-wide associationstudies (GWASs) have not identified any robustgenetic risk factors for isolated dystonia.Objective:The objective of this study was to perform alarge-scale GWAS in a well-characterized, multicenter sample of >6000 individuals to identify genetic risk fac-tors for isolated dystonia. Methods:Array-based GWASs were performed onautosomes for 4303 dystonia participants and 2362healthy control subjects of European ancestry with sub-group analysis based on age at onset, affected bodyregions, and a newly developed clinical score. Another736 individuals were used for validation. Results:This GWAS identified no common genome-wide significant loci that could be replicated despitesufficient power to detect meaningful effects. Poweranalyses imply that the effects of individual variantsare likely very small. Conclusions:Moderatesingle-nucleotidepolymor-phism-based heritability indicates that common variantsdo not contribute to isolated dystonia in this cohort.Sequence-basedGWASs(eg,bywhole-genome sequencing) might help to better understand the geneticbasis. (c) 2024 The Author(s).Movement Disorderspubli-shed by Wiley Periodicals LLC on behalf of InternationalParkinson and Movement Disorder Society.

In the literature on human action control, it is assumed that features of stimuli (S) and responses (R) are integrated into internal representations (so-called event files) that are involved in the execution of an action. Experimentally, the impact of this integration on action control is typically analyzed via S-R binding effects. Recent theorizing in the BRAC framework (Frings et al., 2020) suggests to disentangle the processes of S-R binding proper from S-R retrieval as two independent components contributing to S-R binding effects. Since the literature on age effects on S-R binding effects is scarce and does not provide information on whether the existing findings about the two processes can be generalized to older age groups, this is the first study addressing the effects of older age separately on S-R binding proper vs. S-R retrieval. In two established variants of S-R binding tasks (cumulative n = 262), we contrasted binding (by using a saliency manipulation at the time of binding proper) versus retrieval processes (by manipulating the onset of the distractor at the time of retrieval), replicating previous results in younger (18-30 years) and also in older healthy controls (50-70 years). We therefore found no evidence for age effects on S-R binding proper or S-R retrieval. We thus conclude that the processes contributing to S-R binding effects are - at least in the age groups analyzed in this study - robust and ageindependent. Statement of significance: In human action control, binding proper and retrieval of features in stimulus-response episodes typically lead to so-called S-R binding effects. Against the background of recent theorizing, binding proper and retrieval should be studied independently. In this article, we ran a younger and an older age group and analyzed possible age-related differences in integration or retrieval. Both groups showed the expected pattern for binding and retrieval as expected from the literature.

INTRODUCTION:Magnetic resonance neurography (MRN) and myography (MRM) are emerging imaging methods for detecting diseases of the peripheral nerve system (PNS). Most patients with PNS diseases also undergo needle electromyography (EMG). This study examined whether EMG led to lesions that were detectable using MRN/MRM and whether these lesions could impair image interpretation. METHODS:Ten patients who underwent clinically indicated EMG were recruited. MRN/MRM was performed before and 2-6 h after EMG, and if achievable, 2-3 days later. T2 signal intensity (SI) of the tibialis anterior muscle (TA) was quantified, and sizes and SI of the new lesions were measured. Visual rating was performed independently by three neuroradiologists. RESULTS:T2 lesions at the site of needle insertion, defined as focal edema, were detectable in 9/10 patients. The mean edema size was 31.72 mm2 (SD = 14.42 mm2 ) at the first follow-up. Susceptibility-weighted imaging lesions, defined as (micro) hematomas were detected in 5/10 patients (mean size, 23.85 mm2 [SD = 12.59 mm2 ]). General muscle SI of the TA did not differ between pre- and post-EMG examinations. Lesions size was relatively small, and the readers described image interpretation as not impaired by these lesions. DISCUSSION:This study showed that focal edema and hematomas frequently occurred after needle EMG and could be observed using MRN/MRM. As general muscle SI was not affected and image interpretation was not impaired, we concluded that needle EMG did not interfere with MRN/MRM.

BACKGROUND:The occurrence of tics is the main basis for the diagnosis of Gilles de la Tourette syndrome (GTS). Video-based tic assessments are time consuming. OBJECTIVE:The aim was to assess the potential of automated video-based tic detection for discriminating between videos of adults with GTS and healthy control (HC) participants. METHODS:The quantity and temporal structure of automatically detected tics/extra movements in videos from adults with GTS (107 videos from 42 participants) and matched HCs were used to classify videos using cross-validated logistic regression. RESULTS:Videos were classified with high accuracy both from the quantity of tics (balanced accuracy of 87.9%) and the number of tic clusters (90.2%). Logistic regression prediction probability provides a graded measure of diagnostic confidence. Expert review of about 25% of lower-confidence predictions could ensure an overall classification accuracy above 95%. CONCLUSIONS:Automated video-based methods have a great potential to support quantitative assessment and clinical decision-making in tic disorders.

AbstractPurposeShort-read genome sequencing (GS) is a comprehensive genetic testing method capable of detecting multiple variant types. Despite its technical advantages, systemic comparisons of singleton GS (sGS), trio GS (tGS), and exome sequencing-based standard-of-care (SoC) in real-world diagnostics remain limited.MethodsWe systematically compared sGS, tGS, and SoC genetic testing in 448 patients with rare diseases in a blinded, prospective study. Three independent teams evaluated the diagnostic yield, variant detection capabilities, and clinical feasibility of GS as a first-tier test. Diagnostic yield was assessed through both prospective and retrospective analyses.ResultsIn prospective analyses, tGS achieved the highest diagnostic yield for likely pathogenic/pathogenic variants (36.8%) in a newly trained team, outperforming the experienced SoC team (36.0%) and the sGS team (30.4%). Retrospective analyses, accounting for technical variant detection and team experience differences, reported diagnostic yields of 38.6% for SoC, 41.3% for sGS, and 42.2% for tGS. GS excelled in identifying deep intronic, non-coding, and small copy-number variants missed by SoC. Notably, tGS additionally identified three de novo variants classified as likely pathogenic based on recent GeneMatcher collaborations and newly published gene-disease association studies.ConclusionGS, particularly tGS, demonstrated superior diagnostic performance, supporting its use as a first-tier genetic test. sGS offers a cost-effective alternative, enabling faster, more efficient diagnoses for rare disease patients.

BackgroundPathogenic variants in several genes have been linked to genetic forms of isolated or combined dystonia. The phenotypic and genetic spectrum and the frequency of pathogenic variants in these genes have not yet been fully elucidated, neither in patients with dystonia nor with other, sometimes co-occurring movement disorders such as Parkinson's disease (PD).ObjectivesTo screen >2000 patients with dystonia or PD for rare variants in known dystonia-causing genes.MethodsWe screened 1207 dystonia patients from Germany (DysTract consortium), Spain, and South Korea, and 1036 PD patients from Germany for pathogenic variants using a next-generation sequencing gene panel. The impact on DNA methylation of KMT2B variants was evaluated by analyzing the gene's characteristic episignature.ResultsWe identified 171 carriers (109 with dystonia [9.0%]; 62 with PD [6.0%]) of 131 rare variants (minor allele frequency <0.005). A total of 52 patients (48 dystonia [4.0%]; four PD [0.4%, all with GCH1 variants]) carried 33 different (likely) pathogenic variants, of which 17 were not previously reported. Pathogenic biallelic variants in PRKRA were not found. Episignature analysis of 48 KMT2B variants revealed that only two of these should be considered (likely) pathogenic.ConclusionThis study confirms pathogenic variants in GCH1, GNAL, KMT2B, SGCE, THAP1, and TOR1A as relevant causes in dystonia and expands the mutational spectrum. Of note, likely pathogenic variants only in GCH1 were also found among PD patients. For DYT-KMT2B, the recently described episignature served as a reliable readout to determine the functional effect of newly identified variants. (c) 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Movement Disorders Clinical PracticeEarly View LETTERS: PUBLISHED ARTICLES Partially Levodopa-Responsive Parkinsonism in a Carrier of a Novel Pathogenic CLTC Variant Tatiana Usnich MD, PhD, Tatiana Usnich MD, PhD orcid.org/0000-0001-7335-8888 Institute of Neurogenetics, University of Lübeck, Lübeck, GermanySearch for more papers by this authorLeonie F. Becker MD, Leonie F. Becker MD Institute of Systems Motor Science, CBBM, University of Lübeck, Lübeck, Germany Department of Pediatrics, University Hospital Medical Center Schleswig-Holstein, Lübeck, GermanySearch for more papers by this authorInga Nagel MD, Inga Nagel MD Institute of Human Genetics, University of Lübeck, Lübeck, GermanySearch for more papers by this authorTobias Bäumer MD, Tobias Bäumer MD Institute of Systems Motor Science, CBBM, University of Lübeck, Lübeck, GermanySearch for more papers by this authorAlexander Münchau MD, Corresponding Author Alexander Münchau MD [email protected] orcid.org/0000-0002-3219-2284 Institute of Systems Motor Science, CBBM, University of Lübeck, Lübeck, Germany Correspondence to: Dr. Alexander Münchau, Institute of Systems Motor Science, Center of Brain, Behavior and Metabolism (CBBM), Ratzeburger Allee 160, 23538 Lübeck, Germany; E-mail: [email protected]Search for more papers by this author Tatiana Usnich MD, PhD, Tatiana Usnich MD, PhD orcid.org/0000-0001-7335-8888 Institute of Neurogenetics, University of Lübeck, Lübeck, GermanySearch for more papers by this authorLeonie F. Becker MD, Leonie F. Becker MD Institute of Systems Motor Science, CBBM, University of Lübeck, Lübeck, Germany Department of Pediatrics, University Hospital Medical Center Schleswig-Holstein, Lübeck, GermanySearch for more papers by this authorInga Nagel MD, Inga Nagel MD Institute of Human Genetics, University of Lübeck, Lübeck, GermanySearch for more papers by this authorTobias Bäumer MD, Tobias Bäumer MD Institute of Systems Motor Science, CBBM, University of Lübeck, Lübeck, GermanySearch for more papers by this authorAlexander Münchau MD, Corresponding Author Alexander Münchau MD [email protected] orcid.org/0000-0002-3219-2284 Institute of Systems Motor Science, CBBM, University of Lübeck, Lübeck, Germany Correspondence to: Dr. Alexander Münchau, Institute of Systems Motor Science, Center of Brain, Behavior and Metabolism (CBBM), Ratzeburger Allee 160, 23538 Lübeck, Germany; E-mail: [email protected]Search for more papers by this author First published: 08 April 2024 https://doi.org/10.1002/mdc3.14037 Potential conflict of interest: The authors declare no conflict of interest relevant to this work. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References 1Nardecchia F, Bove R, Pollini L, Giannini MT, Manti F, De Giorgi A, et al. Improvement of movement disorder and neurodevelopment under selegiline in a CLTC-deficient patient. Mov Disord Clin Pract 2023; 10: 1430–1432. 10.1002/mdc3.13834 PubMedGoogle Scholar 2Hamdan FF, Myers CT, Cossette P, et al. High rate of recurrent De novo mutations in developmental and epileptic encephalopathies. Am J Hum Genet 2017; 101(5): 664–685. 10.1016/j.ajhg.2017.09.008 CASPubMedWeb of Science®Google Scholar 3Manti F, Nardecchia F, Barresi S, et al. Neurotransmitter trafficking defect in a patient with clathrin (CLTC) variation presenting with intellectual disability and early-onset parkinsonism. Park Relat Disord 2019; 61(October 2018): 207–210. 10.1016/j.parkreldis.2018.10.012 PubMedWeb of Science®Google Scholar 4Robinson MS. Forty years of Clathrin-coated vesicles. Traffic 2015; 16(12): 1210–1238. 10.1111/tra.12335 CASPubMedWeb of Science®Google Scholar 5Klein C, Hattori N, Marras C. MDSGene: closing data gaps in genotype-phenotype correlations of monogenic Parkinson's disease. J Parkinsons Dis 2018; 8: S25–S30. 10.3233/JPD-181505 CASPubMedWeb of Science®Google Scholar Early ViewOnline Version of Record before inclusion in an issue ReferencesRelatedInformation