Myoclonus-dystonia Syndrome Research Articles

Bilateral globus pallidus internus-deep brain stimulation in a 5-year-old boy with SGCE-related myoclonus dystonia syndrome.

Bilateral globus pallidus internus-deep brain stimulation in a 5-year-old boy with SGCE-related myoclonus dystonia syndrome.

Синдром миоклонус-дистонии: клинические проявления, эффективность терапии на примере 11 случаев

Введение. Синдром миоклонус-дистонии (СМД) – группа генетически гетерогенных недегенеративных клинических состояний, характеризующихся сочетанием миоклонуса и дистонии в качестве единственных или наиболее выраженных симптомов. Цель. Проанализировать клинические проявления и эффективность терапии СМД у 11 пациентов. Материалы и методы. Ретроспективно проанализированы данные 11 пациентов (6 – мужского пола) из 10 семей, которым был выставлен диагноз СМД. Медиана возраста на момент развития первых симптомов заболевания составила 3 года [IQR: 3,0; 12,5], на момент выполнения исследования – 21 год [IQR: 19,0; 38,0]. Эффективность терапии оценивали следующим образом: полное купирование симптомов – высоко-эффективен, купировано более 50% симптомов – эффективен, менее 50% – частично эффективен, без влияния на симптомы заболевания – неэффективен. Результаты. Первым симптомом заболевания в 72,7% случаев являлся миоклонус, в 27,3% – дистония. Миоклонус в 87,5% наблюдений первично возникал в верхних конечностях. На момент последнего неврологического осмотра у 100% пациентов имелись как миоклонический, так и дистонический гиперкинезы. У 90,9% пациентов отмечалась фокальная либо сегментарная дистония, у 9,1% – генерализованная. В 54,5% случаев были зафиксированы дополнительные экстрапирамидные нарушения. У 57,1% опрошенных наблюдались сопутствующие психиатрические симптомы. В 18,2% случаев симптомы заболевания полностью купировались приемом алкоголя. В 50,0% наблюдений отмечался отягощенный наследственный анамнез по схожим гиперкинезам. В 100% случаев применялась симптоматическая медикаментозная терапия. Использовались противосудорожные препараты (ПСП) – 90,9%, миорелаксанты – 90,9%, ноотропные препараты – 90,9%, препараты леводопы – 72,7%, бензодиазепины – 63,6%, инъекции ботулотоксина – 27,3%, антихолинергические средства – 27,3% и ингибиторы везикулярного переносчика моноаминов 2-го типа – 27,3%. Были эффективны: ПСП – 20,0%, бензодиазепины – 14,3%, препараты леводопы – 12,5%. Продемонстрировали частичный эффект: ПСП – 70,0%, миорелаксанты – 30,0%, бензодиазепины – 28,6%. Инъекции ботулотоксина имели высокую эффективность в отношении дистонии в 100% случаев использования. Оперативное лечение по имплантации электродов для DBS выполнялось 3 (27,3%) пациентам и было эффективно в 33,3% случаев, высокоэффективно – в 66,7%. Выводы. Средний возраст дебюта заболевания приходится на первую декаду жизни. Пациенты часто имеют отягощенный наследственный анамнез по схожим двигательным расстройствам. Первым симптомом обычно является миоклонический гиперкинез в верхних конечностях. К третьей декаде жизни все пациенты имеют как миоклонус, так и дистонию. Медикаментозное лечение ограничено достаточно низкой эффективностью. Высокую эффективность демонстрируют инъекции ботулотоксина, DBS. Introduction. Myoclonus-dystonia syndrome (MDS) is a group of heterogeneous, non- degenerative clinical conditions characterized by a combination of myoclonus and dystonia as the only or most prominent symptoms. Purpose. To analyze the clinical manifestations and effectiveness of therapy for MDS in 11 patients. Materials and methods. Information of 11 patients (6 males) with MDS diagnose from 10 families were retrospectively analyzed. The age of first symptoms of the disease is 3 years [IQR: 3.0; 12.5], age at the time of analysis – 21 years [IQR: 19.0; 38.0]. The effectiveness of therapy was assessed as follows: complete relief of symptoms – highly effective, relief of more than 50% – effective, less than 50% – partially effective, without affecting the symptoms of the disease – not effective. Results. The first symptom of the disease in 72.7% of cases was myoclonus, in 27.3% – dystonia. Myoclonus in 87.5% of cases primarily occurred in the upper extremities. At the time of the last neurological examination, 100% of patients had both myoclonic and dystonic hyperkinesis. 90.9% of patients had focal or segmental dystonia, and 9.1% had generalized dystonia. In 54.5% of cases, additional extrapyramidal disorders were recorded. 57.1% of respondents had concomitant psychiatric symptoms. In 18.2% of cases, the symptoms of the disease were completely stopped by taking alcohol. In 50.0% of cases, there was a burdened hereditary history of similar hyperkinesis. In 100% of cases, symptomatic drug therapy was used. Anticonvulsants were used – 90.9%, muscle relaxants – 90.9%, nootropic drugs – 90.9%, levodopa drugs – 72.7%, benzodiazepines – 63.6%, botulinum toxin injections – 27.3%, anticholinergic agents – 27.3% and the second type of monoamine vesicular transporter inhibitors – 27.3%. Were effective: anticonvulsants – 20.0%, benzodiazepines – 14.3%, levodopa drugs – 12.5%. Demonstrated a partial effect: anticonvulsants – 70.0%, muscle relaxants – 30.0%, benzodiazepines – 28.6%. Botulinum toxin injections were highly effective against dystonia in 100% of cases of use. Surgical treatment for implantation of electrodes for DBS was performed in 3 (27.3%) patients and was effective in 33.3% of cases, highly effective – in 66.7%. Conclusions. The average age of the onset of the disease falls on the first decade of life. Patients often have a burdened hereditary history of similar motor disorders. Usually the first symptom is myoclonic hyperkinesis in the upper extremities. By the third decade of life, all patients have both myoclonus and dystonia. Medical treatment is limited by a rather low efficiency. High efficiency are demonstrated by botulinum toxin injections, DBS.

The expanding genetic landscape of myoclonus-dystonia syndrome: YY1 and ATP1A3 are added to the list

The expanding genetic landscape of myoclonus-dystonia syndrome: YY1 and ATP1A3 are added to the list

Translating Genetic Discovery into a Mechanistic Understanding of Pediatric Movement Disorders: Lessons from Genetic Dystonias and Related Disorders.

The era of next-generation sequencing has increased the pace of gene discovery in the field of pediatric movement disorders. Following the identification of novel disease-causing genes, several studies have aimed to link the molecular and clinical aspects of these disorders. This perspective presents the developing stories of several childhood-onset movement disorders, including paroxysmal kinesigenic dyskinesia, myoclonus-dystonia syndrome, and other monogenic dystonias. These stories illustrate how gene discovery helps focus the research efforts of scientists trying to understand the mechanisms of disease. The genetic diagnosis of these clinical syndromes also helps clarify the associated phenotypic spectra and aids the search for additional disease-causing genes. Collectively, the findings of previous studies have led to increased recognition of the role of the cerebellum in the physiology and pathophysiology of motor control-a common theme in many pediatric movement disorders. To fully exploit the genetic information garnered in the clinical and research arenas, it is crucial that corresponding multi-omics analyses and functional studies also be performed at scale. Hopefully, these integrated efforts will provide us with a more comprehensive understanding of the genetic and neurobiological bases of movement disorders in childhood.

Bilateral Pallidal Stimulation in a Family With Myoclonus Dystonia Syndrome Due to a Mutation in the Sarcoglycan Gene

ObjectivesThe study aimed to present a family with myoclonus dystonia (M-D) syndrome due to a mutation in the epsilon sarcoglycan gene (SGCE). Three members of the family suffered from treatment-refractory severe myoclonic jerks of the neck, trunk, and upper extremities. The mild dystonic symptoms recognized as cervical dystonia or truncal dystonia affected all individuals. The efficacy of pharmacotherapy, including anticholinergic, dopaminergic, and serotoninergic drugs, has failed. One individual developed an alcohol dependency and suffered from alcoholic epilepsy. Materials and MethodsThe patients were referred for stereotactic surgery. All individuals underwent bilateral implantation of deep brain stimulation (DBS) leads into the posteroventrolateral segment of the globus pallidus internus (GPi). Surgeries were uneventful. The formal preoperative objective assessment included the Unified Myoclonus Rating Scale (UMRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). The postoperative UMRS and BFMDRS assessments were done only under continuous stimulation at 3, 6, and 12 months after the surgery and at the last available follow-up ranging from 6 to 15 months (mean, 10 months follow-up). ResultsAt the last follow-up visit, the rest and action parts of UMRS were improved by 93.3% and 88.2%, respectively, when compared to the baseline scores. The motor and disability scales of BFMDRS were improved by 77% and 43% at the last follow-up visit compared to the baseline BFMDRS scores. There were no hardware or stimulation-induced complications over the follow-up period. Positive social adjustment allowed two patients to regain jobs and one patient continued his education and hobbies. ConclusionOur experience gathered in three individuals in the family with a mutation in SGCE indicates that bilateral GPi DBS can be an effective and safe treatment for disabling pharmacological resistant, intractable M-D syndrome.

Effect of the R126C mutation on the structure and function of the glucose transporter GLUT1: A molecular dynamics simulation study

Glucose transporter 1 (GLUT1) is responsible for basal glucose uptake and is expressed in most tissues under normal conditions. GLUT1 mutations can cause early-onset absence epilepsy and myoclonus dystonia syndrome (MDS), with MDS potentially lethal. In this study, the effect of the R126C mutation, which is associated with MDS, on structural stability and substrate transport of GLUT1 was investigated. Various bioinformatics tools were used to predict the stability of GLUT1, revealing that the R126C mutation reduces the structural stability of GLUT1. Molecular dynamics (MD) simulations were used to further characterize the effect of the R126C mutation on GLUT1 structural stability. Based on the MD simulations, specific conformational changes and dominant motions of the GLUT1 mutant were characterized by Principal component analysis (PCA). The mutation disrupts hydrogen bonds between substrate-binding residues and glucose, thus likely reducing substrate affinity. The R126C mutation reduces the conformational stability of the protein, and fewer intramolecular hydrogen bonds were present in the mutated GLUT1 when compared with that of wild-type GLUT1. The mutation increased the free energy of glucose transport through GLUT1 significantly, especially at the mutation site, indicating that passage of glucose through the channel is hindered, and this mutant may even release cytoplasmic glucose. This study provides a detailed atomic-level explanation for the reduced structural stability and substrate transport capacity of a GLUT1 mutant. The results aid our understanding of the structure of GLUT1 and provide a framework for developing drugs to treat GLUT1-related diseases, such as MDS.

A Clinical Approach to the Patients with Combination of Dystonia and Myoclonus

Myoclonus–dystonia syndrome is one of the well-defined “combined dystonia” syndromes, now observed in many conditions, including genetic and acquired. With widespread access to next-generation sequencing techniques, the list of genetic diseases manifesting as combined dystonia with myoclonus continues to expand. In this article, we aim to review different etiologies of combined dystonia with myoclonus. We searched databases such as PubMed, OMIM, and Gene Review using the keywords “dystonia and myoclonus” and “myoclonus–dystonia” to identify such disorders. We identified different acquired and genetic disorders manifesting with the combination of dystonia and myoclonus, with or without other movement disorders, irrespective of the predominant movement disorder. In addition, we propose the diagnostic algorithms for children and adults with myoclonus and dystonia, based on clinical manifestations to guide diagnostic procedures and further management.

Myoclonus-dystonia syndrome due to GNAO1 mutation: a case report

Introduction: Myoclonus-dystonia syndrome (MDS) is an autosomal-dominant movement disorder characterized by childhood-onset myoclonic jerks and dystonic symptoms. The estimated prevalence for MDS is 1/500.000 and usually it is associated with mutations in the epsilon-sarcoglycan (SGCE) gene. One rarer genetic cause for MDS is the GNAO1 mutation. Cytogenetically located on 16q13, this gene encodes a specific subclass of G protein, a signal-transducing molecule important to the central and peripheral nervous system. This heterotrimeric guanine nucleotide-binding protein is composed of alpha, beta, and gamma subunits. The GNAO1 gene usually encodes for G-alpha-o, one of the four subclasses of the G-alpha subunit. GNAO1 variants can cause a wide clinical spectrum and the two major characteristic features caused by them are early-onset epileptic encephalopathies (EOEEs) and involuntary movements without seizures. Genetic testing for GNAO1 should be considered in patients with EOEE or involuntary movement with severe developmental delay. Objective: Our report is about a 2 years old female patient with MDS due to GNAO1 mutation, a rare genetic condition. The aim of the present case report is to highlight the relevance of genetic testing for GNAO1 in cases of MDS. Case Report: A 2-years-old female patient diagnosed with the Myoclonus-dystonia syndrome due to GNAO1 mutation presented multifocal dystonia and severe myoclonic jerks. GNAO1 is located on chromosome 16 (not X-linked) and the mutation was found by whole exome sequencing. The alteration in the position chr16.56.385.308 resulted from a G to A substitution. The glutamine at codon 246 was replaced with lysine. In addition, the electroencephalogram detected myoclonia with no loss of consciousness. In spite of the absence of epileptic encephalopathy, this neurodevelopmental disorder interferes with her daily tasks, particularly breastfeeding. Low doses of rivotril had been attempted for small periods of time. It is expected that, at the age of six years, she undergoes a neurosurgery to insert DBS (deep brain stimulation) in the internal globus pallidus (GPi). DBS is an effective treatment for even the severe MDS and surgery at an early stage may predict a better outcome.

Mutation in ε-Sarcoglycan Induces a Myoclonus-Dystonia Syndrome-Like Movement Disorder in Mice.

Myoclonus dystonia syndrome (MDS) is an inherited movement disorder, and most MDS-related mutations have so far been found in the ε-sarcoglycan (SGCE) coding gene. By generating SGCE-knockout (KO) and human 237 C > T mutation knock-in (KI) mice, we showed here that both KO and KI mice exerted typical movement defects similar to those of MDS patients. SGCE promoted filopodia development in vitro and inhibited excitatory synapse formation both in vivo and in vitro. Loss of function of SGCE leading to excessive excitatory synapses that may ultimately contribute to MDS pathology. Indeed, using a zebrafish MDS model, we found that among 1700 screened chemical compounds, Vigabatrin was the most potent in readily reversing MDS symptoms of mouse disease models. Our study strengthens the notion that mutations of SGCE lead to MDS and most likely, SGCE functions to brake synaptogenesis in the CNS.

KCTD17-related myoclonus-dystonia syndrome: clinical and electrophysiological findings of a patient with atypical late onset

IntroductionMyoclonus-dystonia is a rare syndrome typically occurring during childhood or adolescence, mainly due to SGCE pathogenic variants. Early-onset, atypical presentations of myoclonus-dystonia have recently been associated with KCTD17 variants. In these cases, laryngeal involvement was reported in the advanced stages. MethodsWe evaluated a 52-year-old man with myoclonus-dystonia and positive family history. He underwent an electromyographic investigation of vocal cord and forearm muscles. Whole-exome sequencing was also performed. ResultsOnset of symptoms was at 51 years with dysphonia and vocal tremor. Electromyography disclosed abductor spasmodic dysphonia and laryngeal myoclonus. The patient later developed writer's cramp, upper limb myoclonus, and blepharospasm. Botulinum toxin injection led to improvement of the writer's cramp and to a lesser extent of the spasmodic dysphonia. Genetic analysis identified a heterozygous missense variant in exon 2 of KCTD17: c.229 C > A (p.Leu77Ile), consistently predicted as damaging. ConclusionsWe suggest that the KCTD17-associated phenotypic spectrum may include late onset (even in late adulthood) as well as early and prominent laryngeal involvement.

Clinical phenotype heterogeneity in a family with ε-sarcoglycan gene mutation

This paper describes six cases of patients with myoclonus-dystonia syndrome who are members of a family in which an SGCE gene mutation has been confirmed. Myoclonus-dystonia syndrome is a very rare disease, with an incidence in Europe of about 2 in every million. Due to the fact that only a few case reports of this illness are accessible in the literature, the material we collected seems to be valuable for clinical practice. A history was taken, and physical and genetic examinations of the patients were performed. Furthermore, the clinical examination of three patients was video-recorded. The clinical picture of the disease varied significantly between the described individuals, from a healthy carrier of the SGCE mutation to patients presenting mild to moderate symptoms. The differences concerned the age at onset of the disease, the initial symptoms, the intensity of involuntary movements, and the predominant symptoms. In addition to the typical movement disorders which are myoclonus and dystonia, in the described family there was also the coexistence of epilepsy, obsessive-compulsive behaviour, dyslexia, dysgraphia, non-harmonious development of cognitive processes, as well as mild phenotypic features of muscular dystrophy. The mutation (NM_001099401.2:c.806-809delACTG) found in the presented family has not been described elsewhere. Our description of six cases of patients demonstrates the heterogeneity of the natural course of the disease, even in patients with the same mutation. It seems reasonable to regularly examine relatives of patients with myoclonus-dystonia syndrome, who should be observed for involuntary movements as well as non-motor symptoms.

Clinical and genetic analysis of childhood-onset myoclonus dystonia syndrome caused by SGCE variants

Objective: To explore the clinical characteristics and genotyping results of childhood-onset myoclonus dystonia syndrome caused by SGCE variants. Methods: The clinical data of 9 children with SGCE-related myoclonus dystonia syndrome admitted at either the Department of Neurology, Beijing Children's Hospital, Capital Medical University or the Department of Pediatrics, Peking University First Hospital from May 2018 to October 2019 were collected and the patients were followed up. The definite diagnosis was made on the basis of whole exome sequencing and multiple ligation-dependent probe amplification. The clinical features and gene test results were analyzed retrospectively. Results: Data of 9 patients (4 boys and 5 girls) diagnosed as myoclonus dystonia syndrome caused by SGCE variants were collected. The onset age ranged from 1 year to 3 years and 2 months. The first symptom was myoclonus in 4 cases, while dystonia in the remaining 5 cases. In the course of the disease, 9 cases had myoclonus and 8 had dystonia. Myoclonic jerks were characterized by involuntary jerks in both upper limbs in 8 patients. Six patients had involuntary jerks of lower limbs, resulting in gait instability or even falling. The myoclonus was exacerbated during the fine motor activities, emotional stress or fatigue. Dystonia was characterized by abnormal gait, including 5 cases with right leg dystonia, and 3 cases with the left leg dystonia. Three probands had a positive family history. Intellectual development was normal in all cases. There was no obvious abnormality in video-electroencephalogram (EEG) during both ictal and interictal periods. Electromyography (EMG) and brain magnetic resonance imaging (MRI) of 9 patients were normal. Nine patients carried SGCE gene variants, including 3 frame shift variants, 2 nonsense variants, 2 missense variants, 1 fragment deletion variant and 1 splice site variant. Seven variants were inherited paternally, and 2 variants were de novo. Madopar was used in 8 patients, and nitrazepam in 4 patients, leading to the decrease in the myoclonus jerks and improvement of gait in 6 and 2 patients, respectively. Conclusions: SGCE gene variants can cause myoclonus dystonia syndrome. The onset of the disease may occur at infancy or preschool age, with either myoclonic jerks or dystonia as the initial symptom. Non-epileptic myoclonus is the prominent symptom, with upper limb mainly involved. Most of the patients have the accompanying symptoms of dystonia, and some of them may have spontaneous symptom relief. SGCE gene is imprinted maternally, and the inherited variants of SGCE are paternal in origin.

Deep brain stimulation for myoclonus dystonia syndrome: a meta-analysis with individual patient data.

Good outcomes have been reported in deep brain stimulation (DBS) for myoclonus-dystonia syndrome (M-D), a heritable disease characterized by childhood-onset myoclonic jerks and dystonia in the upper body. This meta-analysis was to evaluate the clinical outcomes consecutively, compare the stimulation targets, and identify potential prognostic factors. A systematic literature search was performed on PubMed, Web of Science, and Embase. The primary outcome was the percent improvement in Burke-Fahn-Marsden Dystonia Rating Scale movement (BFMDRS-M) scores for dystonia and Unified Myoclonus Rating Scale (UMRS) scores for myoclonus at the last follow-up visit. BFMDRS-disability scores of the patients were also summarized. Pearson correlation analyses were performed to identify the myoclonus and dystonia outcome predictors. Thirty-one studies reporting 71 patients were included. There were significant improvements in BFMDRS-M and BFMDRS-disability scores in each time category and at the last follow-up visit. Mean improvement (%) in UMRS was 79.5 ± 18.2, and 94.1% of the patients showed > 50% improvement in UMRS scores at the last follow-up visit. There was a significant trend toward improved myoclonus outcome with older age at onset and shorter disease duration. Most of the adverse events were mild and transient, and pallidal stimulation seemed to be better with respect to fewer stimulation-induced events. Based on the current data, DBS is effective for even the severe M-D. Surgery at an early stage may predict a better outcome. Although targets do not serve as the outcome predictors, pallidal stimulation may be preferred due to fewer stimulation-induced events.

Screening for SGCE mutations in Moroccan sporadic patients with Myoclonus-Dystonia syndrome

Screening for SGCE mutations in Moroccan sporadic patients with Myoclonus-Dystonia syndrome

A retrospective analysis of the prevalence of imprinting disorders in Estonia from 1998 to 2016.

Imprinting disorders (ImpDis) represent a small group of rare congenital diseases primarily affecting growth, development, and the hormonal and metabolic systems. The aim of present study was to identify the prevalence of the ImpDis in Estonia, to describe trends in the live birth prevalence of these disorders between 1998 and 2016, and to compare the results with previously published data. We retrospectively reviewed the records of all Estonian patients since 1998 with both molecularly and clinically diagnosed ImpDis. A prospective study was also conducted, in which all patients with clinical suspicion for an ImpDis were molecularly analyzed. Eighty-seven individuals with ImpDis were identified. Twenty-seven (31%) of them had Prader-Willi syndrome (PWS), 15 (17%) had Angelman syndrome (AS), 15 (17%) had Silver-Russell syndrome (SRS), 12 (14%) had Beckwith-Wiedemann syndrome (BWS), 10 (11%) had pseudo- or pseudopseudohypoparathyroidism, four had central precocious puberty, two had Temple syndrome, one had transient neonatal diabetes mellitus, and one had myoclonus-dystonia syndrome. One third of SRS and BWS cases fulfilled the diagnostic criteria for these disorders, but tested negative for genetic abnormalities. Seventy-six individuals were alive as of January 1, 2018, indicating the total prevalence of ImpDis in Estonia is 5.8/100,000 (95% CI 4.6/100,000-7.2/100,000). The minimum live birth prevalence of all ImpDis in Estonia in 2004-2016 was 1/3,462, PWS 1/13,599, AS 1/27,198, BWS 1/21,154, SRS 1/15,866, and PHP/PPHP 1/27,198. Our results are only partially consistent with previously published data. The worldwide prevalence of SRS and GNAS-gene-related ImpDis is likely underestimated and may be at least three times higher than expected.

Screening for SGCE mutations in Moroccan sporadic patients with Myoclonus-Dystonia syndrome

Myoclonus-Dystonia (M-D) is a rare autosomal-dominant movement disorder characterized by myoclonic jerks in combination with dystonia and psychiatric features. Mutations in the Epsilon-sarcoglycan (SGCE, DYT11) gene have been found to cause M-D in 30%–50% of familial M-D. Sporadic cases have also been reported. The aim of study was to investigate whether the M-D phenotype is associated with the existence of SGCE mutations in Moroccan sporadic patients with M-D syndrome. The study included 12 M-D patients. We sequenced the entire coding region of the SGCE gene. We identified two different heterozygous SGCE mutations (c.769A > C ; c.391-3T > C). Our finding confirm that SGCE mutations can occur in sporadic patients when the phenotype is consistent with M-D. Further functional studies are needed to show how changes in SGCE protein function lead to the M–D phenotype.

Thalamus Stimulation for Myoclonus Dystonia Syndrome: Five Cases and Long-Term Follow-up

Myoclonic dystonia syndrome (MDS) is a rare inherited movement disorder characterized by the coexistence of myoclonic jerks and dystonia. Deep brain stimulation (DBS) is a promising treatment for patients with MDS that targets the globus pallidus internus or ventral intermediate nucleus (Vim) of the thalamus. However, there are few studies regarding the long-term effects of Vim DBS in patients with MDS and even fewer in those without gene mutations. Two positive and three negative SGCE mutation patients presenting with predominant myoclonus underwent Vim DBS. The Unified Myoclonus Rating Scale and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) were assessed pre- and postoperation. Over an average follow-up period of 50 months, the myoclonus improvement rate was 92.7%. The average improvement in the BFMDRS motor score was 71.4% and the average improvement in the BFMDRS disabling score was 75.8%. This study suggests that Vim DBS can be a safe and effective treatment option for patients with MDS. Vim DBS alone may be preferable for patients with myoclonus-dominated MDS regardless of the identification of an SGCE mutation. Additional globus pallidus internus DBS may be used for progressive dystonia after Vim DBS.

Delineating cerebellar mechanisms in DYT11 myoclonus-dystonia.

Recent research has highlighted the role of the cerebellum in the pathophysiology of myoclonus-dystonia syndrome as a result of mutations in the ɛ-sarcoglycan gene (DYT11). Specifically, a cerebellar-dependent saccadic adaptation task is dramatically impaired in this patient group. The objective of this study was to investigate whether saccadic deficits coexist with impairments of limb adaptation to provide a potential mechanism linking cerebellar dysfunction to the movement disorder within symptomatic body regions. Limb adaptation to visuomotor (visual feedback rotated by 30°) and forcefield (force applied by robot to deviate arm) perturbations were examined in 5 patients with DYT11 and 10 aged-matched controls. Patients with DYT11 successfully adapted to both types of perturbation. Modelled and averaged summary metrics that captured adaptation behaviors were equivalent to the control group across conditions. DYT11 is not characterized by a uniform deficit in adaptation. The previously observed large deficit in saccadic adaption is not reflected in an equivalent deficit in limb adaptation in symptomatic body regions. We suggest potential mechanisms at the root of this discordance and identify key research questions that need future study. © 2018 International Parkinson and Movement Disorder Society.

Uniparental disomy causing Myoclonus Dystonia Syndrome associated with Russell Silver Syndrome: a case report (P6.033)

Uniparental disomy causing Myoclonus Dystonia Syndrome associated with Russell Silver Syndrome: a case report (P6.033)

A novel SGCE gene mutation in a Moroccan sporadic case with myoclonus-dystonia syndrome

Inherited myoclonus-dystonia syndrome (MDS) is a rare autosomal-dominant movement disorder characterized by myoclonic jerks and dystonia accompanied with psychiatric manifestations that begin in the first two decades of life. Mutations in epsilon-sarcoglycan (SGCE) gene which encodes the SGCE protein represent a major genetic cause of MDS. We report a sporadic MDS case with abnormal movements including myoclonus and dystonic symptoms affecting the upper body then the neck. In addition, obsessive compulsive disorder (OCD) was observed. This heterogeneous phenotype was shown to be associated with a novel heterozygous mutation within the exon 6 of SGCE gene (c.812G>T).