Paroxysmal Kinesigenic Dyskinesia in Twins With Chromosome 16p11.2 Duplication Syndrome.
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ABSTRACT:
SUBMITTER: Ueda K
PROVIDER: S-EPMC8112851 | biostudies-literature | 2021 Feb
REPOSITORIES: biostudies-literature
Publications
Paroxysmal Kinesigenic Dyskinesia in Twins With Chromosome 16p11.2 Duplication Syndrome.
Ueda Keisuke K Shinawi Marwan M Pearson Toni S TS
Neurology. Genetics 20210111 1
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Project description:Background and objectivesIsolated paroxysmal kinesigenic dyskinesia (PKD) is mainly caused by PRRT2 variants and TMEM151A variants. Patients with proximal 16p11.2 microdeletion (16p11.2MD) (including PRRT2) often have neurodevelopmental phenotypes, whereas a few patients have PKD. Here, we aimed to identify 16p11.2MD in patients with PKD and describe the related phenotypes.MethodsWhole-exome sequencing and bioinformatics analysis of copy number variant (CNV) were performed in patients with PKD carrying neither PRRT2 nor TMEM151A variant. Quantitative PCR and low-coverage whole-genome sequencing verified the CNV.ResultsWe identified 9 sporadic patients with PKD and 16p11.2MD (∼535 kb), accounting for 9.6% (9/94) of our patients. Together with 9 previously reported patients with PKD and 16p11.2MD, we found that 16p11.2MD was de novo in 11 of 12 tested patients and inherited from a parent in the other patient. And 80% (12/15) of these patients had a mild language delay, 64.3% (9/14) had compromised learning ability, 42.9% (6/14) had a mild motor delay, and 50% (6/12) had abnormal neuroimaging findings. No severe autism disorders were observed.DiscussionMild developmental problems may be overlooked. A detailed inquiry of developmental history and CNV testing are necessary to distinguish patients with 16p11.2MD from isolated PKD.
| S-EPMC8855691 | biostudies-literature
Project description:Paroxysmal kinesigenic choreoathetosis (PKC), the most frequently described type of paroxysmal dyskinesia, is characterized by recurrent, brief attacks of involuntary movements induced by sudden voluntary movements. Some patients with PKC have a history of infantile afebrile convulsions with a favorable outcome. To localize the PKC locus, we performed genomewide linkage analysis on eight Japanese families with autosomal dominant PKC. Two-point linkage analysis provided a maximum LOD score of 10.27 (recombination fraction [theta] =.00; penetrance [p] =.7) at marker D16S3081, and a maximum multipoint LOD score for a subset of markers was calculated to be 11.51 (p = 0.8) at D16S3080. Haplotype analysis defined the disease locus within a region of approximately 12.4 cM between D16S3093 and D16S416. P1-derived artificial chromosome clones containing loci D16S3093 and D16S416 were mapped, by use of FISH, to 16p11.2 and 16q12.1, respectively. Thus, in the eight families studied, the chromosomal localization of the PKC critical region (PKCR) is 16p11.2-q12.1. The PKCR overlaps with a region responsible for "infantile convulsions and paroxysmal choreoathetosis" (MIM 602066), a recently recognized clinical entity with benign infantile convulsions and nonkinesigenic paroxysmal dyskinesias.
| S-EPMC1288380 | biostudies-literature
Project description:IntroductionMutations of the PRRT2 gene are the most common cause for paroxysmal kinesigenic dyskinesia. However, patients with negative PRRT2 mutations are not rare. The aim of this study is to determine whether copy number variant of PRRT2 gene is another potential pathogenic mechanism in the patients with paroxysmal kinesigenic dyskinesia with negative PRRT2 point and frameshift mutations.MethodsWe screened PRRT2 copy number variants using the AccuCopy™ method in 29 patients with paroxysmal kinesigenic dyskinesia with negative PRRT2 point and frameshift mutations. Next-generation sequencing was used to determine the chromosomal deletion sites in patients with PRRT2 copy number variants, and to exclude mutations in other known causative genes for paroxysmal kinesigenic dyskinesia.ResultsTwo sporadic patients with negative PRRT2 point and frameshift mutations (6.9%) were identified to have de novo PRRT2 copy number deletions (591 and 832 Kb deletions located in 16p11.2). The two patients presented with pure paroxysmal kinesigenic dyskinesia and paroxysmal kinesigenic dyskinesia and benign infantile convulsions, respectively. They had normal intelligence and neuropsychiatric development, in contrast to those previously reported with 16p11.2 deletions complicated with neuropsychiatric disorders. No correlation between the deletion ranges and phenotypic variations was found.Conclusion16p11.2 deletions play causative roles in paroxysmal kinesigenic dyskinesia, especially for sporadic cases. Our findings extend the phenotype of 16p11.2 deletions to pure paroxysmal kinesigenic dyskinesia. Screening for 16p11.2 deletions should thus be included in genetic evaluations for patients with paroxysmal kinesigenic dyskinesia.
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Project description:Paroxysmal kinesigenic dyskinesia (PKD) is characterized by recurrent and brief attacks of dystonia or chorea precipitated by sudden movements. It can be sporadic or familial. Proline-Rich Transmembrane Protein 2 (PRRT2) has been shown to be a common causative gene of PKD. However, less than 50% of patients with primary PKD harbor mutations in PRRT2. The aim of this study is to use eight families with PKD to identify the pathogenic PRRT2 mutations, or possible novel genetic cause of PKD phenotypes. After extensive clinical investigation, direct sequencing and mutation analysis of PRRT2 were performed on patients from eight PKD families. A genome-wide STR and SNP based linkage analysis was performed in one large family that is negative for pathogenic PRRT2 mutations. Using additional polymorphic markers, we identified a novel gene locus on chromosome 3q in this PRRT2-mutation-negative PKD family. The LOD score for the region between markers D3S1314 and D3S1256 is 3.02 and we proposed to designate this locus as Episodic Kinesigenic Dyskinesia (EKD3). Further studies are needed to identify the causative gene within this locus.
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Project description:Paroxysmal kinesigenic dyskinesia (PKD) is associated with a disturbance of neural circuit and network activities, while its neurophysiological characteristics have not been fully elucidated. This study utilized the high-density electroencephalogram (hd-EEG) signals to detect abnormal brain activity of PKD and provide a neural biomarker for its clinical diagnosis and PKD progression monitoring. The resting hd-EEGs are recorded from two independent datasets and then source-localized for measuring the oscillatory activities and function connectivity (FC) patterns of cortical and subcortical regions. The abnormal elevation of theta oscillation in wildly brain regions represents the most remarkable physiological feature for PKD and these changes returned to healthy control level in remission patients. Another remarkable feature of PKD is the decreased high-gamma FCs in non-remission patients. Subtype analyses report that increased theta oscillations may be related to the emotional factors of PKD, while the decreased high-gamma FCs are related to the motor symptoms. Finally, the authors established connectome-based predictive modelling and successfully identified the remission state in PKD patients in dataset 1 and dataset 2. The findings establish a clinically relevant electroencephalography profile of PKD and indicate that hd-EEG can provide robust neural biomarkers to evaluate the prognosis of PKD.
| S-EPMC10966565 | biostudies-literature
Project description:Paroxysmal kinesigenic dyskinesia (PKD) is characterized by transient and recurrent involuntary movements that are triggered by a sudden movement. Here, we report an elderly female patient with a 1-month history of paroxysmal rigidity of the right limb. As the symptoms were characterized as paroxysmal, transient, and repetitive, her condition was initially thought to be epilepsy. Subsequent examinations showed no abnormality in the continuous video-electroencephalogram (EEG) monitoring, magnetic resonance imaging (MRI), fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT), and genetic testing. The final diagnosis was identified as clinically diagnosed PKD, and the symptoms were well controlled after oxcarbazepine treatment. To our knowledge, this is the first report to show elderly-onset PKD. This case expands our understanding of the age of onset of PKD. However, it is necessary to differentiate PKD from reflex epilepsy and hysteria attacks. For patients with typical clinical manifestations, we should adhere to the standard diagnostic workflow for the efficient diagnosis of PKD, aiming at avoiding misdiagnosis and mistreatment.
| S-EPMC9588133 | biostudies-literature
Project description:Paroxysmal kinesigenic dyskinesia (PKD) is characterized by sudden episodes of involuntary movements. PKD is a very rare movement disorder, and correct clinical diagnosis is often a challenge.We present the case of a 23-year-old female with PKD. The patient showed episodes of twisting movements for 3 years. The symptoms lasted for about 5-10 minutes and subsided spontaneously. She was diagnosed as having epilepsy, and depressive and anxiety disorders successively. However, her symptoms did not alleviate after taking sodium valproate and antidepressants. Though there were no mutations in her PRRT2 gene, carbamazepine was used for treatment and was effective in controlling her symptoms.The clinical features of PKD patients are not always typical; therefore, it is important to distinguish PKD from the other subtypes of paroxysmal dyskinesia and psychogenic disorders.
| S-EPMC5993030 | biostudies-other
Project description:Paroxysmal kinesigenic dyskinesia (PKD) is a movement disorder, with an excellent response to carbamazepine treatment. It has been described in various populations, but not yet in an African population. In a patient who reported to clinic with side effects of carbamazepine, PRRT2 gene screening was performed based on a clinical history compatible with PKD. A common PRRT2 mutation was identified in this patient, hereby the first genetically confirmed PRRT2-associated PKD in Africa. Reporting genetic confirmation of an unusual movement disorder from an equally unusual location shows the wide geographical distribution of PRRT2-associated disease. It also illustrates recognizability of this treatable disorder where the easiest accessible diagnostic tool is neurological history and examination.
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