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Mutations in the gene encoding the dopamine-synthetic enzyme GTP cyclohydrolase-1 (GCH1) cause DOPA-responsive dystonia (DRD). Mencacci et al. demonstrate that GCH1 variants are associated with an increased risk of Parkinson's disease in both DRD pedigrees and in patients with Parkinson's disease but without a family history of DRD.
Familial Adult Myoclonic Epilepsy (FAME) is a genetically heterogeneous disorder characterized by cortical tremor and seizures. Intronic TTTTA/TTTCA repeat expansions in SAMD12 (FAME1) are the main cause of FAME in Asia. Using genome sequencing and repeat-primed PCR, we identify another site of this repeat expansion, in MARCH6 (FAME3) in four European families. Analysis of single DNA molecules with nanopore sequencing and molecular combing show that expansions range from 3.3 to 14 kb on average. However, we observe considerable variability in expansion length and structure, supporting the existence of multiple expansion configurations in blood cells and fibroblasts of the same individual. Moreover, the largest expansions are associated with micro-rearrangements occurring near the expansion in 20% of cells. This study provides further evidence that FAME is caused by intronic TTTTA/TTTCA expansions in distinct genes and reveals that expansions exhibit an unexpectedly high somatic instability that can ultimately result in genomic rearrangements.
Within the broad spectrum of movement disorders, tics and functional tic-like movements belong to a particular clinical category. Both types of movements are within the range of normal movement kinematics and muscle synergies, but appear repetitive and without appropriate context embedment. Historically, there have been many attempts to separate the 2 types of movements, but because of their phenomenological overlap, clinical distinction may be prone to error, and misdiagnoses may often occur. Most importantly, the 2 types of movement may coexist. Here, we review the available literature on the 2 types of motor phenomena and demonstrate some of the difficulties in distinguishing tics from functional tic-like movements on clinical grounds. We also highlight similarities and differences in pathophysiologic characteristics, documenting the significance of action monitoring, attentional allocation, and behavioral reinforcement in both types of movements, as well as in their risk factors. We discuss the overlap of current behavioral treatments for tics and functional tic-like movements and emphasize implications of diagnostic mislabeling. Such implications include the need to tailor behavioral treatment approaches to individual phenomenological profiles and guiding decision making for severe patients requiring invasive interventions, such as deep brain stimulation. A deeper insight from clinicians with respect to persisting challenges in classifying and differentiating these motor phenomena could accelerate the development of reliable clinical and physiologic markers (i.e., next generation phenotyping) and a neurobiology-driven therapeutic approach for these motor phenomena.
The observed relationship between severity of premonitory urges and interoceptive awareness suggests that interoception might be involved in self-reported premonitory urges in GTS. High levels of interoceptive awareness might reflect a self-attentive capacity to perceive urges.
IntroductionKnowledge regarding tremor prevalence and phenomenology in patients with adult-onset primary dystonia is limited. Dystonic tremor is presumably under-reported, and we aimed to assess the prevalence and the clinical correlates of tremor in patients with adult-onset primary dystonia.MethodsWe enrolled 473 consecutive patients with different types of adult-onset primary dystonia. They were assessed for presence of head tremor and arm tremor (rest, postural and kinetic).ResultsA total of 262 patients (55.4%) were tremulous: 196 patients presented head tremor, 140 patients presented arm tremor and 98 of them had a combination of head and arm tremor. Of the 140 patients with arm tremor, all presented postural tremor, 103 patients (73.6%) presented also a kinetic component, whereas 57 patients (40.7%) had rest tremor. Rest tremor was unilateral/asymmetric in up to 92.9% of them. Patients with segmental and multifocal dystonia were more likely tremulous than patients with focal dystonia. Dystonic symptoms involving the neck were more frequently observed in patients with head tremor, whereas dystonic symptoms involving the arms were more frequently observed in patients with arm tremor.DiscussionHere we show that tremor is a common feature of patients with adult-onset primary dystonia. It may involve different body segments, with the head being the most commonly affected site. Arm tremor is also frequent (postural>kinetic>rest), occurring in up to one-third of cases. There is a suggestion of a stronger tendency for spread of dystonic features in patients with associated tremor. Dystonic tremor is under-reported and this underscores the importance of careful clinical examination when assessing tremulous patients without overt dystonia.
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