Localization and Mutation Detection for Paroxysmal Kinesigenic Choreoathetosis

Backgrounds Paroxysmal kinesigenic choreoathetosis (PKC) is an autosomal-dominant movement disorder characterized by attacks of paroxysmal involuntary movements. To date, the causative gene has not been discovered. Purpose The purpose of the study is to localize the causative region and detect the causative mutation. Methods A PKC family including 16 subjects (5 cases and 11 controls) in Zhejiang Province was recruited. Nine microsatellite markers on chromosome 16 were selected and genotyped. Two-point LOD scores were calculated. After preliminary localization, CACNG3, IL4R and ABCC11 were selected as candidate genes and were detected by polymerase chain reaction-sequencing or PCR-denaturing high performance liquid chromatography (PCR-DHPLC). Results The maximal two-point LOD score was obtained in D16S3081 with 1.21, and haplotype analysis revealed almost all of individuals carrying 5-3-8-3-4-2-5-5-6 in D16S3093/D16S685/D16S690/D16S3081/D16S3080 D16S411/D16S3136/D16S3112/D16S3057 were affected by PKC. There were no causative mutation in CACNG3, IL4R and ABCC11 genes. Conclusions The culprit gene for PKC was located in ~19.34 cM region between 16p12.1–q13, and CACNG3, IL4R and ABCC11 were all ruled out as the cause.     

Familial Paroxysmal Kinesigenic Choreoathetosis: An Electrophysiologic and Genotypic Analysis

PURPOSE: We report a pedigree of familial paroxysmal kinesigenic choreoathetosis (PKC) in which five of 18 members are affected. The pathophysiologic basis for PKC is still uncertain; reflex epilepsy versus dysfunction of basal ganglia. We examined (a) whether there were ictal discharges during the attacks, and (b) a linkage between PKC and possible DNA markers linked to several familial epileptic or movement disorders. METHODS: Video-monitoring EEG was performed in two patients with PKC during attacks elicited by movements of the lower extremities. Blood samples for DNA studies were obtained from 15 members of the pedigree. Fourteen polymorphic markers on chromosomes 1p, 2q, 6p, 10q, and 20q were genotyped, and two-point lod scores were calculated for each marker under a dominant model. RESULTS: No ictal discharges were found during the attacks in both patients. We could not obtain significant linkage of PKC with any marker examined. CONCLUSIONS: The video-monitoring EEG findings in our cases strongly suggested that the etiology of PKC should be considered distinct from that of reflex epilepsy. However, the patients in this pedigree had experienced generalized convulsions in their infancies; thus we could not deny the possibility of an epileptogenic basis for PKC. There was no strong evidence for a linkage of the gene for PKC with the candidate regions on 1p, 2q, 6p, 10q, or 20q.     

Paroxysmal kinesigenic choreoathetosis. Case report

A case of sporadic, idiopathic, paroxysmal kinesigenic choreoathetosis is described. The frequent attacks triggered by the initial phase of voluntary movement responded well to treatment with diphenylhydantoin. The nosological, etiopathogenetic, clinical and therapeutic aspects of paroxysmal choreoathetosis are discussed and the literature reviewed.

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Sommario Viene descritto un caso di Coreoatetosi Parossistica Kinesigenica, in forma sporadica, idiopatica, con frequenti attacchi scatenati dalla fase iniziale del movimento volontario, con buona risposta terapeutica alla difenilidantoina. Vengono discussi gli aspetti nosologici, etiopatogenetici, clinici e terapeutici relativi alla Coreoatetosi Parossistica, con revisione dei dati della letteratura in proposito.

     

Ten Year Follow-up of Paroxysmal Choreoathetosis: A Sporadic Case Becomes Familial

A 30-year-old woman is reported who was originally described in 1967 as an isolated instance of paroxysmal choreoathetosis. In the subsequent 10 years, her movement disorder has decreased in severity. However, she now has a 7-year-old daughter with a similar but more persistent and more serious condition. This family emphasizes both variability of manifestations of paroxysmal choreoathetosis and the importance of genetic factors.     

中国人婴儿惊厥伴发作性手足舞蹈徐动征临床特征分析

目的探讨我国婴儿惊厥伴发作性手足舞蹈徐动征(ICCA)患者的临床特点。方法分析诊断为ICCA的5例患者的临床表现、脑电图(EEG)、影像学和治疗转归的临床资料。ICCA的入选标准为：3～20个月出现良性婴儿惊厥(BFIC)和在儿童后期或青春期出现发作性运动源性运动障碍(PKC)。结果5例ICCA患者来自4个家系,男性4例,女性1例。BFIC发病年龄在8～12个月,PKC发病年龄在5岁以后,影像学未见异常,部分患者EEG有局限性放电和慢波增多。卡马西平、苯妥英、拉莫三嗪治疗有效。其中2例合并继发性癫痫。ICCA家系中其他发作性疾病患者共9例。结论ICCA可能为常染色体显性遗传疾病,我国该病患者同时具有BFIC和PKC的特征性表现和治疗转归特点,家系中可能有PKC和其他类型的癫痫患者,说明PKC与癫痫之间可能存在某些相似的发病机理,此还有待于进一步研究。     

发作性运动障碍（附8例临床报道）

目的 :总结发作性运动障碍中PKC的临床特征 ,并对其发病机制加以探讨。方法 :对 8例PKC患者临床表现及实验室资料进行分析。结果 :本组中 8例患者发病年龄 8～ 14岁 ,病程 1～ 10年 ,87%为男性。临床表现均由突发运动诱发 ,由久坐、久立后突然改变体位 ,表现为一侧或双侧不自主肢体舞动、躯干扭动和面部异常运动 ,持续数秒钟自行缓解 ,发作时意识清楚 ,2例EEG轻度异常 ,6例正常EEG中有 2例 2 4h动态脑电图示样放电 ,8例服用少量卡马西平完全控制发作。结论 :PKC是发作性运动障碍中一类疾病 ,以开始运动时出现发作性锥体外系症状为特点 ,发作范围局部或全身 ,是可以治愈的 ,抗癫药治疗效果良好     

阵发性运动障碍25例临床分析

目的总结阵发性运动障碍患者的诱发因素、临床特征以及治疗特点。方法收集阵发性运动障碍患者25例,均进行神经科常规检查以及视频脑电和核磁共振扫描,部分患者进行单光子发射计算机断层扫描,并对其诱发因素、发病年龄以及临床表现进行分析,观察对抗癫药物治疗的效果。结果25例患者中,散发14例,有家族史患者8例,继发性3例。其中阵发性运动源性舞蹈样徐动症/运动障碍共19例,对小剂量卡马西平治疗有显著效果。结论不同类型的阵发性运动障碍诱发因素不同,对卡马西平的治疗效果也不同;继发性阵发性运动障碍要重视原发病治疗。     

The Pathogenesis of Paroxysmal Kinesigenic Dyskinesia: Current Concepts

Paroxysmal kinesigenic dyskinesia (PKD) is a movement disorder characterized by recurrent and transient episodes of involuntary movements, including dystonia, chorea, ballism, or a combination of these, which are typically triggered by sudden voluntary movement. Disturbance of the basal ganglia-thalamo-cortical circuit has long been considered the cause of involuntary movements. Impairment of the gating function of the basal ganglia can cause an aberrant output toward the thalamus, which in turn leads to excessive activation of the cerebral cortex. Structural and functional abnormalities in the basal ganglia, thalamus, and cortex and abnormal connections between these brain regions have been found in patients with PKD. Recent studies have highlighted the role of the cerebellum in PKD. Insufficient suppression from the cerebellar cortex to the deep cerebellar nuclei could lead to overexcitation of the thalamocortical pathway. Therefore, this literature review aims to provide a comprehensive overview of the current research progress to explore the neural circuits and pathogenesis of PKD and promote further understanding and outlook on the pathophysiological mechanism of movement disorders. © 2023 International Parkinson and Movement Disorder Society.     

Paroxysmal Kinesigenic Segmental Myoclonus due to a spinal cord glioma.

We report an 18-year-old man with paroxysmal jerking movements of the left arm since age 7 years. These were invariably precipitated by startle or sudden movements. He was subsequently diagnosed with a cervical cord anaplastic astrocytoma on MRI. We could not identify previous reports of paroxysmal myoclonus secondary to a spinal cord neoplasm. We have coined the term Paroxysmal Kinesigenic Segmental Myoclonus to describe this entity.     

Paroxysmal kinesigenic choreoathetosis because of cryptogenic myelitis. Remission with carbamazepine and the pathogenetic role of altered sodium channels

Lesions of the spinal cord causing paroxysmal kinesigenic choreoathetosis are rare and most of the reported cases have been because of multiple sclerosis. We now describe this movement disorder occurring in a patient who developed a myelitis of unknown aetiology. A typically striking remission followed treatment with carbamazepine. It is suggested that the effect of the drug and the disorder itself may both be explained on the basis of altered sodium channels.     

Paroxysmal kinesigenic choreoathetosis: evidence of linkage to the pericentromeric region of chromosome 16 in four Chinese families

Background: Paroxysmal kinesigenic choreoathetosis (PKC) is an autosomal dominant condition characterized by abnormal involuntary movements precipitated by sudden movement. The pericentromeric region of chromosome 16 has been linked to PKC by several reports. This study was to localize and identify PKC gene in four Chinese PKC families. Methods: Genetic linkage mapping with eight markers spanning chromosome 16p12‐q13 was performed in 43 family members. Genome‐wide single nucleotide polymorphism (SNP) scans were performed on four individuals in Family 1 in which infantile convulsion (IC) was co‐inherited with PKC. Results: Individuals in Family 1 presented with both IC and paroxysmal choreoathetosis (ICCA), and Families 2, 3, and 4 presented only with PKC. Evidence for linkage was found with a maximum two‐point LOD score of 4.89 for D16S690 (θ = 0.0) and a maximum multipoint LOD score was 5.34 between D16S3080 and D16S3136. Haplotype analysis showed the disease locus was between D16S3093 and D16S3057. A total of 84 SNPs spanned on 16q12.1‐q13 was not segregated with the PKC phenotype, which defined an unlinked region from rs9933187 to rs8044753. Thus, the critical region of the PKC gene is across the pericentromeric region of chromosome 16, and most likely maps to a region of 20.5 Mb (6.2 cM) between D16S3093 and rs9933187 (16p11.2‐q12.1). Conclusion: The assignment of the locus for PKC to the pericentromeric region of chromosome 16 is confirmed and putatively narrowed in the present study.     

Event-related brain potentials in paroxysmal kinesigenic choreoathetosis

Event-related brain potentials (ERPs) were recorded in a 30 year old female patient with familial kinesigenic choreoathetosis and a group of control subjects. In line with previous observations the patient exhibited an enhanced amplitude of the early component of the contingent negative variation of the ERP in a two stimulus paradigm. Moreover, a greatly enhanced P3 amplitude was found in auditory and visual classification (oddball) paradigms. These results suggest a general upregulation of widespread subcortical projection systems leading to both, abnormal movements and abnormally high amplitudes of ERPs.     

发作性运动障碍(附33例临床分析和文献复习)

目的　了解发作性运动障碍的临床特点以及治疗方法。方法　分析 33例发作性运动障碍病例的临床表现和实验室检查。结果　 (1)发作性运动诱发性运动障碍 (PKD) 32例 (96 .97% ) ;(2 )发作性非运动诱发性运动障碍 (PNKD) 3例 (9.0 9% ) ;(3)发作性过度运动导致的运动障碍 (PED) 6例 (18.18% ) ;(4)发作性睡眠诱发性运动障碍 (PHD) 3例 (9.0 9% )。除 2 4例为单纯 PKD外 ,其余病例均与其它类型互相重叠。 EEG大多正常 (32 /33) ,32例 CT/MRI正常。部分可合并癫痫 (5 /33) ,抗癫痫治疗多数 (2 9/33)有效。结论　发作性运动障碍是一种少见的运动障碍疾病 ,和癫痫有一定关系 ,各型可互相重叠 ,EEG大多正常 ,大部分抗癫痫药物治疗有效。     

全面性癫癎伴热性惊厥附加症的临床和脑电图特征分析

目的探讨全面性癫伴热性惊厥附加症(GEFS )的临床和脑电图(EEG)特点。方法收集4个GEFS 的家系资料,通过详细的调查建立完善的家系谱,并对受累者的临床资料、EEG进行分析总结。结果4个家系共有60名成员,其中受累者20例,表现为FS者5例,FS 者7例,FS 与失神发作2例,FS 与肌阵挛发作1例,FS 与失神和肌阵挛发作1例,此例患者发作间期EEG呈现局灶性癫放电和全面性癫放电共存的现象,1例表现为FS 和部分性发作,其发作间歇期EEG呈现中央中颞棘波灶,个体诊断符合良性罗兰多区癫。另外,受累者有肯定的临床发作,但是由于不能收集到可靠的发作表现资料,无法进行发作分类者3例。受累者神经系统检查以及头颅CT或磁共振成像(MRI)检查均未见异常。结论GEFS 的正确诊断需要注重个体,立足于整个家系进行,其临床发作谱还包括部分性发作,脑电图也有局灶的癫样放电。良性罗兰多区癫也许是GEFS 的一个新表现型。