Clinical case studies and reporting are important to the discovery of new disorders and the advancement of medical sciences. Both clinicians and basic scientists play equally important roles leading to treatment discoveries for both cures and symptoms. In the field of movement disorders, exceptional observation of patients from clinicians is imperative, not just for phenomenology but also for the variable occurrences of these disorders, along with other signs and symptoms, throughout the day and the disease course. The Movement Disorders in Asia Task Force (TF) was formed to help enhance and promote collaboration and research on movement disorders within the region. As a start, the TF has reviewed the original studies of the movement disorders that were preliminarily described in the region. These include nine disorders that were first described in Asia: Segawa disease, PARK-Parkin, X-linked dystonia-parkinsonism, dentatorubral-pallidoluysian atrophy, Woodhouse-Sakati syndrome, benign adult familial myoclonic epilepsy, Kufor-Rakeb disease, tremulous dystonia associated with mutation of the calmodulin-binding transcription activator 2 gene, and paroxysmal kinesigenic dyskinesia. We hope that the information provided will honor the original researchers and help us learn and understand how earlier neurologists and basic scientists together discovered new disorders and made advances in the field, which impact us all to this day.
{"title":"Nine Hereditary Movement Disorders First Described in Asia: Their History and Evolution.","authors":"Priya Jagota, Yoshikazu Ugawa, Zakiyah Aldaajani, Norlinah Mohamed Ibrahim, Hiroyuki Ishiura, Yoshiko Nomura, Shoji Tsuji, Cid Diesta, Nobutaka Hattori, Osamu Onodera, Saeed Bohlega, Amir S N AlDin, Shen-Yang Lim, Jee-Young Lee, Beomseok Jeon, Pramod Kumar Pal, Huifang Shang, Shinsuke Fujioka, Prashanth Lingappa Kukkle, Onanong Phokaewvarangkul, Chin-Hsien Lin, Cholpon Shambetova, Roongroj Bhidayasiri","doi":"10.14802/jmd.23065","DOIUrl":"10.14802/jmd.23065","url":null,"abstract":"<p><p>Clinical case studies and reporting are important to the discovery of new disorders and the advancement of medical sciences. Both clinicians and basic scientists play equally important roles leading to treatment discoveries for both cures and symptoms. In the field of movement disorders, exceptional observation of patients from clinicians is imperative, not just for phenomenology but also for the variable occurrences of these disorders, along with other signs and symptoms, throughout the day and the disease course. The Movement Disorders in Asia Task Force (TF) was formed to help enhance and promote collaboration and research on movement disorders within the region. As a start, the TF has reviewed the original studies of the movement disorders that were preliminarily described in the region. These include nine disorders that were first described in Asia: Segawa disease, PARK-Parkin, X-linked dystonia-parkinsonism, dentatorubral-pallidoluysian atrophy, Woodhouse-Sakati syndrome, benign adult familial myoclonic epilepsy, Kufor-Rakeb disease, tremulous dystonia associated with mutation of the calmodulin-binding transcription activator 2 gene, and paroxysmal kinesigenic dyskinesia. We hope that the information provided will honor the original researchers and help us learn and understand how earlier neurologists and basic scientists together discovered new disorders and made advances in the field, which impact us all to this day.</p>","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/a3/d4/jmd-23065.PMC10548072.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9994082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nongenetic movement disorders are common throughout the world. The movement disorders encountered may vary depending on the prevalence of certain disorders across various geographical regions. In this paper, we review historical and more common nongenetic movement disorders in Asia. The underlying causes of these movement disorders are diverse and include, among others, nutritional deficiencies, toxic and metabolic causes, and cultural Latah syndrome, contributed by geographical, economic, and cultural differences across Asia. The industrial revolution in Japan and Korea has led to diseases related to environmental toxin poisoning, such as Minamata disease and β-fluoroethyl acetate-associated cerebellar degeneration, respectively, while religious dietary restriction in the Indian subcontinent has led to infantile tremor syndrome related to vitamin B12 deficiency. In this review, we identify the salient features and key contributing factors in the development of these disorders.
{"title":"Historical and More Common Nongenetic Movement Disorders From Asia.","authors":"Norlinah Mohamed Ibrahim, Priya Jagota, Pramod Kumar Pal, Roongroj Bhidayasiri, Shen-Yang Lim, Yoshikazu Ugawa, Zakiyah Aldaajani, Beomseok Jeon, Shinsuke Fujioka, Jee-Young Lee, Prashanth Lingappa Kukkle, Huifang Shang, Onanong Phokaewvarangkul, Cid Diesta, Cholpon Shambetova, Chin-Hsien Lin","doi":"10.14802/jmd.22224","DOIUrl":"10.14802/jmd.22224","url":null,"abstract":"<p><p>Nongenetic movement disorders are common throughout the world. The movement disorders encountered may vary depending on the prevalence of certain disorders across various geographical regions. In this paper, we review historical and more common nongenetic movement disorders in Asia. The underlying causes of these movement disorders are diverse and include, among others, nutritional deficiencies, toxic and metabolic causes, and cultural Latah syndrome, contributed by geographical, economic, and cultural differences across Asia. The industrial revolution in Japan and Korea has led to diseases related to environmental toxin poisoning, such as Minamata disease and β-fluoroethyl acetate-associated cerebellar degeneration, respectively, while religious dietary restriction in the Indian subcontinent has led to infantile tremor syndrome related to vitamin B12 deficiency. In this review, we identify the salient features and key contributing factors in the development of these disorders.</p>","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/fb/aa/jmd-22224.PMC10548075.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9586814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01Epub Date: 2023-06-13DOI: 10.14802/jmd.23074
Ellen Hertz, Grisel Lopez, Jens Lichtenberg, Dietrich Haubenberger, Nahid Tayebi, Mark Hallett, Ellen Sidransky
Biallelic mutations in GBA1 cause the lysosomal storage disorder Gaucher disease, and carriers of GBA1 variants have an increased risk of Parkinson's disease (PD). It is still unknown whether GBA1 variants are also associated with other movement disorders. We present the case of a woman with type 1 Gaucher disease who developed acute dystonia and parkinsonism at 35 years of age during a recombinant enzyme infusion treatment. She developed severe dystonia in all extremities and a bilateral pill-rolling tremor that did not respond to levodopa treatment. Despite the abrupt onset of symptoms, neither Sanger nor whole genome sequencing revealed pathogenic variants in ATP1A3 associated with rapid-onset dystonia-parkinsonism (RDP). Further examination showed hyposmia and presynaptic dopaminergic deficits in [18F]-DOPA PET, which are commonly seen in PD but not in RDP. This case extends the spectrum of movement disorders reported in patients with GBA1 mutations, suggesting an intertwined phenotype.
{"title":"Rapid-Onset Dystonia and Parkinsonism in a Patient With Gaucher Disease.","authors":"Ellen Hertz, Grisel Lopez, Jens Lichtenberg, Dietrich Haubenberger, Nahid Tayebi, Mark Hallett, Ellen Sidransky","doi":"10.14802/jmd.23074","DOIUrl":"10.14802/jmd.23074","url":null,"abstract":"<p><p>Biallelic mutations in GBA1 cause the lysosomal storage disorder Gaucher disease, and carriers of GBA1 variants have an increased risk of Parkinson's disease (PD). It is still unknown whether GBA1 variants are also associated with other movement disorders. We present the case of a woman with type 1 Gaucher disease who developed acute dystonia and parkinsonism at 35 years of age during a recombinant enzyme infusion treatment. She developed severe dystonia in all extremities and a bilateral pill-rolling tremor that did not respond to levodopa treatment. Despite the abrupt onset of symptoms, neither Sanger nor whole genome sequencing revealed pathogenic variants in ATP1A3 associated with rapid-onset dystonia-parkinsonism (RDP). Further examination showed hyposmia and presynaptic dopaminergic deficits in [18F]-DOPA PET, which are commonly seen in PD but not in RDP. This case extends the spectrum of movement disorders reported in patients with GBA1 mutations, suggesting an intertwined phenotype.</p>","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e5/99/jmd-23074.PMC10548083.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9976984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
1Chulalongkorn Centre of Excellence for Parkinson’s Disease and Related Disorders, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand 2The Academy of Science, The Royal Society of Thailand, Bangkok, Thailand VIEWPOINT https://doi.org/10.14802/jmd.23021 / J Mov Disord 2023;16(3):279-284 pISSN 2005-940X / eISSN 2093-4939
{"title":"From Evidence to the Dish: A Viewpoint of Implementing a Thai-Style Mediterranean Diet for Parkinson's Disease.","authors":"Onanong Phokaewvarangkul, Nitinan Kantachadvanich, Vijittra Buranasrikul, Appasone Phoumindr, Saisamorn Phumphid, Priya Jagota, Roongroj Bhidayasiri","doi":"10.14802/jmd.23021","DOIUrl":"10.14802/jmd.23021","url":null,"abstract":"1Chulalongkorn Centre of Excellence for Parkinson’s Disease and Related Disorders, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand 2The Academy of Science, The Royal Society of Thailand, Bangkok, Thailand VIEWPOINT https://doi.org/10.14802/jmd.23021 / J Mov Disord 2023;16(3):279-284 pISSN 2005-940X / eISSN 2093-4939","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3c/66/jmd-23021.PMC10548080.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9657549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01Epub Date: 2023-07-24DOI: 10.14802/jmd.23085
Taewoo Kim, Su Hyeon Ha, Dallah Yoo, Kyung Sun Park, Tae-Beom Ahn
Dopa-responsive dystonia (DRD) is a rare, treatable disorder caused by the dysfunction of enzymes involved in the biosynthesis of dopamine, leading to dopamine deficiency. 1 The most common form of DRD, also known as Segawa disease, is an autosomal dominant heterozygous variant in the guanosine triphosphate cyclohydrolase-1 ( GCH1 ) gene, resulting in a deficiency of tetra-hydrobiopterin (BH4), an essential cofactor for tyrosine hydroxylase (TH), which catalyzes the rate-limiting step of dopamine synthesis. The typical presentation of Segawa disease is child-hood-onset lower limb dystonia and diurnal fluctuation worsening toward the evening, with an excellent response to low doses of levodopa. However, phenotypic and genetic heterogeneity and sex-specific differences in penetrance frequently lead to misdiagnosis, which delays levodopa treatment and results in permanent orthopedic deformities requiring unnecessary surgical procedures. 2 Oculogyric crises (OGCs) are rare dystonic movement disorders characterized by paroxysmal, conjugate, tonic, and typically upward deviation of the eyes, lasting minutes to hours
{"title":"A Novel Variant of GCH1 in Dopa-Responsive Dystonia With Oculogyric Crises and Intrafamilial Phenotypic Heterogeneity.","authors":"Taewoo Kim, Su Hyeon Ha, Dallah Yoo, Kyung Sun Park, Tae-Beom Ahn","doi":"10.14802/jmd.23085","DOIUrl":"10.14802/jmd.23085","url":null,"abstract":"Dopa-responsive dystonia (DRD) is a rare, treatable disorder caused by the dysfunction of enzymes involved in the biosynthesis of dopamine, leading to dopamine deficiency. 1 The most common form of DRD, also known as Segawa disease, is an autosomal dominant heterozygous variant in the guanosine triphosphate cyclohydrolase-1 ( GCH1 ) gene, resulting in a deficiency of tetra-hydrobiopterin (BH4), an essential cofactor for tyrosine hydroxylase (TH), which catalyzes the rate-limiting step of dopamine synthesis. The typical presentation of Segawa disease is child-hood-onset lower limb dystonia and diurnal fluctuation worsening toward the evening, with an excellent response to low doses of levodopa. However, phenotypic and genetic heterogeneity and sex-specific differences in penetrance frequently lead to misdiagnosis, which delays levodopa treatment and results in permanent orthopedic deformities requiring unnecessary surgical procedures. 2 Oculogyric crises (OGCs) are rare dystonic movement disorders characterized by paroxysmal, conjugate, tonic, and typically upward deviation of the eyes, lasting minutes to hours","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/18/39/jmd-23085.PMC10548081.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10216290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01Epub Date: 2023-06-13DOI: 10.14802/jmd.23035
Debjyoti Dhar, Vikram V Holla, Riyanka Kumari, Neeharika Sriram, Jitender Saini, Ravi Yadav, Akhilesh Pandey, Nitish Kamble, Babylakshmi Muthusamy, Pramod Kumar Pal
Objective: aaMutations in the KMT2B gene have been identified in patients previously diagnosed with idiopathic dystonia. Literature on KMT2B-related dystonia is sparse in the Indian and Asian populations.
Methods: aaWe report seven patients with KMT2B-related dystonia studied prospectively from May 2021 to September 2022. Patients underwent deep clinical phenotyping and genetic testing by whole-exome sequencing (WES). A systematic literature search was performed to identify the spectrum of previously published KMT2B-related disorders in the Asian subcontinent.
Results: aaThe seven identified patients with KMT2B-related dystonia had a median age at onset of four years. The majority experienced onset in the lower limbs (n = 5, 71.4%), with generalization at a median duration of 2 years. All patients except one had complex phenotypes manifesting as facial dysmorphism (n = 4), microcephaly (n = 3), developmental delay (n = 3), and short stature (n = 1). Magnetic resonance imaging (MRI) abnormalities were present in four cases. WES revealed novel mutations in the KMT2B gene in all patients except one. Compared to the largest cohort of patients with KMT2B-related disorders, the Asian cohort, comprising 42 patients, had a lower prevalence of female patients, facial dysmorphism, microcephaly, intellectual disability, and MRI abnormalities. Protein-truncating variants were more prevalent than missense variants. While microcephaly and short stature were more common in patients with missense mutations, facial dysmorphism was more common in patients with truncating variants. Deep brain stimulation, performed in 17 patients, had satisfactory outcomes.
Conclusion: aaThis is the largest series of patients with KMT2B-related disorders from India, further expanding the clinico-genotypic spectrum. The extended Asian cohort emphasizes the unique attributes of this part of the world.
{"title":"KMT2B-Related Dystonia in Indian Patients With Literature Review and Emphasis on Asian Cohort.","authors":"Debjyoti Dhar, Vikram V Holla, Riyanka Kumari, Neeharika Sriram, Jitender Saini, Ravi Yadav, Akhilesh Pandey, Nitish Kamble, Babylakshmi Muthusamy, Pramod Kumar Pal","doi":"10.14802/jmd.23035","DOIUrl":"10.14802/jmd.23035","url":null,"abstract":"<p><strong>Objective: </strong>aaMutations in the KMT2B gene have been identified in patients previously diagnosed with idiopathic dystonia. Literature on KMT2B-related dystonia is sparse in the Indian and Asian populations.</p><p><strong>Methods: </strong>aaWe report seven patients with KMT2B-related dystonia studied prospectively from May 2021 to September 2022. Patients underwent deep clinical phenotyping and genetic testing by whole-exome sequencing (WES). A systematic literature search was performed to identify the spectrum of previously published KMT2B-related disorders in the Asian subcontinent.</p><p><strong>Results: </strong>aaThe seven identified patients with KMT2B-related dystonia had a median age at onset of four years. The majority experienced onset in the lower limbs (n = 5, 71.4%), with generalization at a median duration of 2 years. All patients except one had complex phenotypes manifesting as facial dysmorphism (n = 4), microcephaly (n = 3), developmental delay (n = 3), and short stature (n = 1). Magnetic resonance imaging (MRI) abnormalities were present in four cases. WES revealed novel mutations in the KMT2B gene in all patients except one. Compared to the largest cohort of patients with KMT2B-related disorders, the Asian cohort, comprising 42 patients, had a lower prevalence of female patients, facial dysmorphism, microcephaly, intellectual disability, and MRI abnormalities. Protein-truncating variants were more prevalent than missense variants. While microcephaly and short stature were more common in patients with missense mutations, facial dysmorphism was more common in patients with truncating variants. Deep brain stimulation, performed in 17 patients, had satisfactory outcomes.</p><p><strong>Conclusion: </strong>aaThis is the largest series of patients with KMT2B-related disorders from India, further expanding the clinico-genotypic spectrum. The extended Asian cohort emphasizes the unique attributes of this part of the world.</p>","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/df/cc/jmd-23035.PMC10548078.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9976985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Subacute sclerosing panencephalitis (SSPE) is a slowly progressive central nervous system disorder affecting children and young individuals and is caused by mutant measles virus persistence. Patients with SSPE may present with extrapyramidal manifestations such as tics, dystonia, parkinsonism
{"title":"Pisa Syndrome in Subacute Sclerosing Panencephalitis: A Case Report and Review of the Literature.","authors":"Sandeep Kaur, Amit Shankar Singh, Sudesh Prabhakar, Jeenendra Prakash Singhvi, Harpreet Singh Mann, Arun Kaul","doi":"10.14802/jmd.23052","DOIUrl":"10.14802/jmd.23052","url":null,"abstract":"Subacute sclerosing panencephalitis (SSPE) is a slowly progressive central nervous system disorder affecting children and young individuals and is caused by mutant measles virus persistence. Patients with SSPE may present with extrapyramidal manifestations such as tics, dystonia, parkinsonism","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/57/55/jmd-23052.PMC10548073.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9765046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01Epub Date: 2023-06-09DOI: 10.14802/jmd.23028
Nikola Kresojević, Ivana Perović, Iva Stanković, Aleksandra Tomić, Milica Jecˇmenica Lukic, Vladana Marković, Tanja Stojković, Gorana Mandić, Milena Janković, Ana Marjanović, Marija Branković, Ivana Novaković, Igor Petrović, Nataša Dragašević, Elka Stefanova, Marina Svetel, Vladimir Kostić
Dear Editor, Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by an expansion of CAG trinucleotide repeats in the HTT gene, which encodes the huntingtin protein.1 The normal number of CAG repeats in the HTT gene is between 10 and 26; if there are 27–35 repeats, HD will not occur, but due to meiotic instability, the number of repeats may increase, and the disease may manifest in offspring. A total of 36– 39 repeats represent a gray zone with reduced penetrance, where the symptoms occur only in some individuals. Finally, if there are more than 40 CAG repeats, the penetrance is complete, and the disease will certainly manifest.1 Here, we report the clinical features of patients diagnosed with HD at Neurology Clinic, University Clinical Center of Serbia. A previous publication regarding the survival of HD patients in Republic of Serbia was the result of a follow-up study (from 1982 to 2004) in movement disorders department.2 However, the data presented in the current article were collected from an electronic database, which was introduced in Neurology Clinic, University Clinical Center of Serbia in 2003; therefore, some patients may have been included in both studies. A total of 125 patients were found to have sufficient clinical data, including 53 males (42.4%) and 72 females (57.6%). The average age at disease onset (AAO) in our cohort was 45.4 ± 13.3 years (range 13–82 years), similar to the median age of onset of 43 years found in a larger cohort of 1,766 HD patients.3 Juvenile onset is generally rare, occurring in approximately 5% of HD patients with a high number of trinucleotide CAG repeats (over 60).4 In our cohort, only three patients with 64, 71, and 81 CAG repeats had juvenile onset. The small number of juvenile onset patients in our sample may result from referral bias of the tertiary center for adult patients. A total of 16 (14%) patients had a negative family history of HD, a result similar to the rate of 10% reported in the literature and attributed to the anticipation phenomenon in individuals with an intermediate number of CAG repeats (27–35).1,5 In our sample, the most common initial symptom was chorea in 56% of patients, which occurred at a mean age of 47.4 ± 12.5 years (range 14–82 years); 32% had cognitive-psychiatric symptoms (at 41.5 ± 14.0 years, range 13–70 years), and 8.8% had mixed symptoms (at 49.0 ± 14.0 years, range 23–69 years). A similar distribution of initial symptoms was found in a larger multicenter cohort including 1,766 patients, of whom 48% had motor symptoms, 28% had cognitive-psychiatric symptoms (19.6% with psychiatric symptoms and 8.4% with cognitive symptoms), and 13.2% had mixed symptoms.3 We did not find a difference in the number of CAG repeats when comparing the group of patients with psychiatric symptoms at the disease onset
{"title":"Clinical and Genetic Features of Huntington's Disease Patients From Republic of Serbia: A Single-Center Experience.","authors":"Nikola Kresojević, Ivana Perović, Iva Stanković, Aleksandra Tomić, Milica Jecˇmenica Lukic, Vladana Marković, Tanja Stojković, Gorana Mandić, Milena Janković, Ana Marjanović, Marija Branković, Ivana Novaković, Igor Petrović, Nataša Dragašević, Elka Stefanova, Marina Svetel, Vladimir Kostić","doi":"10.14802/jmd.23028","DOIUrl":"10.14802/jmd.23028","url":null,"abstract":"Dear Editor, Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by an expansion of CAG trinucleotide repeats in the HTT gene, which encodes the huntingtin protein.1 The normal number of CAG repeats in the HTT gene is between 10 and 26; if there are 27–35 repeats, HD will not occur, but due to meiotic instability, the number of repeats may increase, and the disease may manifest in offspring. A total of 36– 39 repeats represent a gray zone with reduced penetrance, where the symptoms occur only in some individuals. Finally, if there are more than 40 CAG repeats, the penetrance is complete, and the disease will certainly manifest.1 Here, we report the clinical features of patients diagnosed with HD at Neurology Clinic, University Clinical Center of Serbia. A previous publication regarding the survival of HD patients in Republic of Serbia was the result of a follow-up study (from 1982 to 2004) in movement disorders department.2 However, the data presented in the current article were collected from an electronic database, which was introduced in Neurology Clinic, University Clinical Center of Serbia in 2003; therefore, some patients may have been included in both studies. A total of 125 patients were found to have sufficient clinical data, including 53 males (42.4%) and 72 females (57.6%). The average age at disease onset (AAO) in our cohort was 45.4 ± 13.3 years (range 13–82 years), similar to the median age of onset of 43 years found in a larger cohort of 1,766 HD patients.3 Juvenile onset is generally rare, occurring in approximately 5% of HD patients with a high number of trinucleotide CAG repeats (over 60).4 In our cohort, only three patients with 64, 71, and 81 CAG repeats had juvenile onset. The small number of juvenile onset patients in our sample may result from referral bias of the tertiary center for adult patients. A total of 16 (14%) patients had a negative family history of HD, a result similar to the rate of 10% reported in the literature and attributed to the anticipation phenomenon in individuals with an intermediate number of CAG repeats (27–35).1,5 In our sample, the most common initial symptom was chorea in 56% of patients, which occurred at a mean age of 47.4 ± 12.5 years (range 14–82 years); 32% had cognitive-psychiatric symptoms (at 41.5 ± 14.0 years, range 13–70 years), and 8.8% had mixed symptoms (at 49.0 ± 14.0 years, range 23–69 years). A similar distribution of initial symptoms was found in a larger multicenter cohort including 1,766 patients, of whom 48% had motor symptoms, 28% had cognitive-psychiatric symptoms (19.6% with psychiatric symptoms and 8.4% with cognitive symptoms), and 13.2% had mixed symptoms.3 We did not find a difference in the number of CAG repeats when comparing the group of patients with psychiatric symptoms at the disease onset","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3e/2e/jmd-23028.PMC10548084.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41176466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01Epub Date: 2023-06-09DOI: 10.14802/jmd.23006
Jinyoung Youn, Elizabeth Slow, Robert Chen, Andres M Lozano, Alfonso Fasano
1Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2Neuroscience Center, Samsung Medical Center, Seoul, Korea 3Edmond J. Safra Program in Parkinson’s Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Health Network, Toronto, ON, Canada 4Division of Neurology, University of Toronto, Toronto, ON, Canada 5Division of Brain, Imaging and Behavior, Systems Neuroscience, University Health Network, University of Toronto, Toronto, ON, Canada 6Krembil Brain Institute, Toronto, ON, Canada 7Division of Neurosurgery, University of Toronto, Toronto, ON, Canada 8Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, ON, Canada LETTER TO THE EDITOR https://doi.org/10.14802/jmd.23006 / J Mov Disord 2023;16(3):325-327 pISSN 2005-940X / eISSN 2093-4939
{"title":"Pallidal Deep Brain Stimulation for Refractory Celiac-Related Myoclonus.","authors":"Jinyoung Youn, Elizabeth Slow, Robert Chen, Andres M Lozano, Alfonso Fasano","doi":"10.14802/jmd.23006","DOIUrl":"10.14802/jmd.23006","url":null,"abstract":"1Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2Neuroscience Center, Samsung Medical Center, Seoul, Korea 3Edmond J. Safra Program in Parkinson’s Disease, Morton and Gloria Shulman Movement Disorders Clinic, Toronto Western Hospital, University Health Network, Toronto, ON, Canada 4Division of Neurology, University of Toronto, Toronto, ON, Canada 5Division of Brain, Imaging and Behavior, Systems Neuroscience, University Health Network, University of Toronto, Toronto, ON, Canada 6Krembil Brain Institute, Toronto, ON, Canada 7Division of Neurosurgery, University of Toronto, Toronto, ON, Canada 8Center for Advancing Neurotechnological Innovation to Application (CRANIA), Toronto, ON, Canada LETTER TO THE EDITOR https://doi.org/10.14802/jmd.23006 / J Mov Disord 2023;16(3):325-327 pISSN 2005-940X / eISSN 2093-4939","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ac/5d/jmd-23006.PMC10548079.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9586815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2023-09-01Epub Date: 2023-07-25DOI: 10.14802/jmd.23098
Sandeep Gurram, Vikram V Holla, Riyanka Kumari, Debjyoti Dhar, Nitish Kamble, Ravi Yadav, Babylakshmi Muthusamy, Pramod Kumar Pal
Dear Editor, Kufor-Rakeb syndrome is a rare autosomal recessive disease, first described in 19941 in the Middle-Eastern country of Jordan. In 2006, biallelic mutations in the ATP13A2 gene were determined to be the underlying genetic etiology.2 More than 50 cases have been reported, including four cases from India.3,4 This syndrome is clinically characterized by juvenile-onset parkinsonism, supranuclear upgaze palsy, cognitive decline, pyramidal signs, visual hallucinations, oculogyric crisis, facial-faucialfinger mini myoclonus and dystonia in various combinations.5-7 In addition, biallelic loss-of-function mutations in the ATP13A2 gene can result in neuronal ceroid lipofuscinosis and complicated hereditary spastic paraplegia type 78 (SPG78).8,9 Here, we expand the phenotypic and genotypic spectrum of KuforRakeb syndrome by reporting dystonic opisthotonus in a patient with juvenile-onset parkinsonism and oculogyric crisis and a novel homozygous variant (NM_022089.4;c.705G>C) in the ATP13A2 gene. An 18-year-old man, born of a 3rd-degree consanguineous marriage (Figure 1), presented with episodes of uprolling of the eyeballs with retained awareness suggestive of oculogyric crisis, slurred speech, and drooling for 2 years and abnormal backward posturing of the trunk and neck while walking for 18 months. These symptoms occurred more frequently in the evenings and were reduced after a short nap. On examination, the patient had normal cognition, hypophonic speech, a reduced blink rate, mild upgaze impairment, and normal saccades and pursuits. He had right-side predominant asymmetrical parkinsonism with rigidity and bradykinesia but no tremor or postural instability. On walking, the patient had dystonic opisthotonus, which was less apparent when standing (Supplementary Video 1 in the online-only Data Supplement, Segment 1). In addition, the patient had hyperreflexia in the lower limbs with normal power and plantar response. The rest of the neurological and systemic examination results were normal. Routine blood investigation results, including hemogram, renal and liver function tests, serum electrolytes, copper and ceruloplasmin and magnetic resonance imaging (MRI) of the brain, were normal (Figure 1). Whole-exome sequencing revealed a novel homozygous missense variant in the ATP13A2 gene (NM_022089.4;c.705G>C;p.Glu235Asp). No other significant variant was found that could explain the clinical findings. The asymptomatic parents were found to be heterozygous carriers (Figure 1). The c.705G>C variant is novel and not reported in population databases. Computational prediction tools predicted that the p.Glu235Asp variant is likely to have functional consequences. According to Sorting Intolerant From Tolerant (SIFT), the variant was predicted to be deleterious (score = 0); PolyPhen-2 predicted it to be damaging (score = 0.983), and the Combined Annotation Dependent Depletion (CADD) score
{"title":"Dystonic Opisthotonus in Kufor-Rakeb Syndrome: Expanding the Phenotypic and Genotypic Spectrum.","authors":"Sandeep Gurram, Vikram V Holla, Riyanka Kumari, Debjyoti Dhar, Nitish Kamble, Ravi Yadav, Babylakshmi Muthusamy, Pramod Kumar Pal","doi":"10.14802/jmd.23098","DOIUrl":"10.14802/jmd.23098","url":null,"abstract":"Dear Editor, Kufor-Rakeb syndrome is a rare autosomal recessive disease, first described in 19941 in the Middle-Eastern country of Jordan. In 2006, biallelic mutations in the ATP13A2 gene were determined to be the underlying genetic etiology.2 More than 50 cases have been reported, including four cases from India.3,4 This syndrome is clinically characterized by juvenile-onset parkinsonism, supranuclear upgaze palsy, cognitive decline, pyramidal signs, visual hallucinations, oculogyric crisis, facial-faucialfinger mini myoclonus and dystonia in various combinations.5-7 In addition, biallelic loss-of-function mutations in the ATP13A2 gene can result in neuronal ceroid lipofuscinosis and complicated hereditary spastic paraplegia type 78 (SPG78).8,9 Here, we expand the phenotypic and genotypic spectrum of KuforRakeb syndrome by reporting dystonic opisthotonus in a patient with juvenile-onset parkinsonism and oculogyric crisis and a novel homozygous variant (NM_022089.4;c.705G>C) in the ATP13A2 gene. An 18-year-old man, born of a 3rd-degree consanguineous marriage (Figure 1), presented with episodes of uprolling of the eyeballs with retained awareness suggestive of oculogyric crisis, slurred speech, and drooling for 2 years and abnormal backward posturing of the trunk and neck while walking for 18 months. These symptoms occurred more frequently in the evenings and were reduced after a short nap. On examination, the patient had normal cognition, hypophonic speech, a reduced blink rate, mild upgaze impairment, and normal saccades and pursuits. He had right-side predominant asymmetrical parkinsonism with rigidity and bradykinesia but no tremor or postural instability. On walking, the patient had dystonic opisthotonus, which was less apparent when standing (Supplementary Video 1 in the online-only Data Supplement, Segment 1). In addition, the patient had hyperreflexia in the lower limbs with normal power and plantar response. The rest of the neurological and systemic examination results were normal. Routine blood investigation results, including hemogram, renal and liver function tests, serum electrolytes, copper and ceruloplasmin and magnetic resonance imaging (MRI) of the brain, were normal (Figure 1). Whole-exome sequencing revealed a novel homozygous missense variant in the ATP13A2 gene (NM_022089.4;c.705G>C;p.Glu235Asp). No other significant variant was found that could explain the clinical findings. The asymptomatic parents were found to be heterozygous carriers (Figure 1). The c.705G>C variant is novel and not reported in population databases. Computational prediction tools predicted that the p.Glu235Asp variant is likely to have functional consequences. According to Sorting Intolerant From Tolerant (SIFT), the variant was predicted to be deleterious (score = 0); PolyPhen-2 predicted it to be damaging (score = 0.983), and the Combined Annotation Dependent Depletion (CADD) score","PeriodicalId":16372,"journal":{"name":"Journal of Movement Disorders","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/63/f7/jmd-23098.PMC10548071.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9919543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}