[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.

Clinical and genetic analysis of childhood-onset myoclonus dystonia syndrome caused by SGCE variants / 中华儿科杂志

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.

Hermann Oppenheim, a pioneer of modern German neurology / Hermann Oppenheim, um pioneiro da moderna neurologia alemã

Hermann Oppenheim (1858-1919) was a leading fgure of the modern German neurology. In spite of the antisemitic ofcial policy, besides his complex personality, he had achieved widespread recognition of his professional qualifcation that attracted neurologists from all around the world to his private clinic. However, he did not held prominent positions at University milieu, in spite of being the main assistant to Karl Westphal (1833­1890) at the Charité-Hospital, in Berlin. Oppenheim was the author of an encyclopedic book of neurology titled "Lehrbuch der Nervenkrankheiten für Ärzte und Studierende" ("Textbook of Nervous Diseases for Doctors and Students"), frst ed., 1894. He also published signifcant works on several disorders, including "traumatic neurosis" (1889) that was criticized by Jean-Martin Charcot (1825­1893), among others. He was clinically responsible for the frst successful removal of brain tumors, including pineal tumor. He coined the term "dystonia musculorum deformans", and he led to several other achievements such as amyotonia congenita ("Oppenheim's disease"), besides Oppenheim's reflex.

Hermann Oppenheim (1858-1919) foi uma fgura importante da moderna neurologia alemã. Apesar da política ofcial anti-semita, além de sua personalidade complexa, ele alcançou amplo reconhecimento de sua qualifcação profssional que atraiu neurologistas de todo o mundo para sua clínica particular. No entanto, ele não ocupou posições de destaque no meio universitário, apesar de ser o principal assistente de Karl Westphal (1833-1890) no Charité-Hospital, em Berlim. Oppenheim foi o autor de um livro enciclopédico de neurologia intitulado "Lehrbuch der Nervenkrankheiten für Ärzte und Studierende" ("Livro Didático de Doenças Nervosas para Médicos e Alunos"), editado em 1894. Ele também publicou trabalhos signifcativos sobre vários distúrbios, incluindo "neurose traumática" ( 1889) que foi criticado por Jean-Martin Charcot (1825­1893), entre outros. Ele foi clinicamente responsável pela primeira remoção bem sucedida de tumores cerebrais, incluindo o tumor pineal. Ele cunhou o termo "distonia musculorumdeformans" e levou a outras várias conquistas como a amiotonia congênita ("doença de Oppenheim"), além do reflexo de Oppenheim.