Another Twist in the Tale: Intrafamilial Phenotypic Heterogeneity in ANO3 ‐Related Dystonia
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Mutations in the anoctamin 3 (ANO3) gene cause autosomal dominant craniocervical dystonia (DYT24), presenting from childhood to mid-life. However, in the past years, the clinical spectrum of this disorder has widened. We present a family with heterogeneous presentation, exemplifying phenotypic diversity in DYT24.The index case presented with myoclonic dystonia at age 10. His family history was remarkable for cervical dystonia with myoclonus in his grandfather, cervical and upper limb dystonia along with dopa-responsive parkinsonism in his father and lower-limb dystonia in his teenage sister. Magnetic resonance imaging and blood work-ups of all the affected family members were normal. The genetic panel for inherited forms of dystonia disclosed a point mutation c.1787C > A (p.Ser596Tyr) segregated in all affected family members.ANO3 mutations usually present with craniocervical dystonia and rarely generalized or leg dystonia. This family exemplifies the heterogeneous presentation of this disorder as well as a wide phenotypic variability within the same family.Keywords:
Paroxysmal dyskinesia
Cervical dystonia
The relation between age at dystonia onset and sex was investigated in 264 patients with cranial-cervical dystonia and 56 patients with upper limb dystonia. In cranial-cervical dystonia, women had a significantly greater age at the onset of dystonia than men. The association was independent of duration of disease and distance of referral, but it was no longer detectable after adjustment for educational level. In upper limb dystonia, men and women did not differ for age at dystonia onset, duration of disease, education level, or distance of referral. A significant inverse association between age at the onset of dystonia and education was observed in both cranial-cervical dystonia and upper limb dystonia series.
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Physical examination findings of dystonia are often underrecognized, especially in the setting of other movement disorders such as essential tremor (ET).A patient with ET exhibited numerous textbook features of cervical dystonia, which were misattributed to ET by a primary care physician and two neurologists.To provide a clear and unmistakable visual example of the clinically significant characteristics of cervical dystonia in the setting of concomitant ET.
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Dystonia is defined as a neurological syndrome characterized by involuntary sustained or intermittent muscle contractions causing twisting, often repetitive movements and postures. Paroxysmal dyskinesias are episodic movement disorders encompassing dystonia, chorea, athetosis and ballism in conscious individuals. Several decades of research have enhanced the understanding of the etiology of human dystonia and dyskinesias that are associated with dystonia, but the pathophysiology remains largely unknown. The spontaneous occurrence of hereditary dystonia and paroxysmal dyskinesia is well documented in rodents used as animal models in basic dystonia research. Several hyperkinetic movement disorders, described in dogs, horses and cattle, show similarities to these human movement disorders. Although dystonia is regarded as the third most common movement disorder in humans, it is often misdiagnosed because of the heterogeneity of etiology and clinical presentation. Since these conditions are poorly known in veterinary practice, their prevalence may be underestimated in veterinary medicine. In order to attract attention to these movement disorders, i.e. dystonia and paroxysmal dyskinesias associated with dystonia, and to enhance interest in translational research, this review gives a brief overview of the current literature regarding dystonia/paroxysmal dyskinesia in humans, and summarizes similar hereditary movement disorders reported in domestic animals.
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Cervical dystonia
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We reviewed the database of the Dystonia Clinic at the University of Kansas Medical Center for patients with dystonia and tremor. Of 296 patients with idiopathic dystonia, 24 had dystonic tremor, 20 with cervical dystonia had an isolated head-nodding tremor, two patients with writer9s cramp had ipsilateral hand tremor, and two patients with generalized dystonia had arm tremor. Eight patients, all with cervical dystonia, had essential tremor that preceded the onset of their dystonia.
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April 26, 2018April 10, 2018Free AccessThe Prevalence of Dystonic Tremor and Tremor Associated with Dystonia in Patients with Cervical Dystonia (P5.049)Lenka Hvizdosova, Martin Nevrly, Pavel Otruba, and Petr KanovskyAuthors Info & AffiliationsApril 10, 2018 issue90 (15_supplement) Letters to the Editor
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Hereditary myoclonus-dystonia (DYT 11) is caused by the epsilon-sarcoglycan (SGCE) mutation. The clinical details and investigations of cases diagnosed with myoclonus-dystonia were reviewed. We describe 5 patients (3 families) with myoclonus-dystonia diagnosed at our center. Majority of the patients had the classical phenotype with few atypical features (adult-onset disease and onset in lower limbs). Four patients carried a mutant variant in the SGCE-gene. A diagnosis of myoclonus-dystonia should be considered in cognitively normal patients with early-onset myoclonus (that may occur both at rest and/or action) with or without dystonia and with or without psychiatric-disturbances.
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Abstract The link between dystonia and tremor has been known for decades, but the question of whether they are two separate illnesses or just different manifestations of one disease with the same pathophysiological background remains unanswered. We distinguish two types of tremor in dystonia: dystonic tremor (DT), which appears on the body part affected by dystonia, and tremor associated with dystonia (TAWD), which appears in locations where the dystonia does not occur. In this study, the frequency of occurrence of different forms of tremor was determined by clinical examination in a group of adult-onset isolated cervical dystonia (CD) patients treated with regular local injections of botulinum toxin A in our department. In total, 120 patients were included in the study, of which 70 (58.3%) had DT of the head. TAWD was, in all 14 cases (11.7%), observed on the upper limbs, in the form of static or intentional tremor. The aim of this study was to point out the presence of TAWD as one of the clinical signs of CD. DT occurred in more than half of the patients and appears to be a relatively common part of the clinical picture in patients with CD.
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Focal dystonia
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Background: Family studies of dystonia may be limited in part by small family size and incomplete ascertainment of dystonia in geographically dispersed families. Further, prevalence estimates of dystonia are believed to be underestimates, as most studies are clinic-based and many individuals do not present to a physician or are misdiagnosed. As a low-cost highly sensitive screening tool is needed to improve case detection for genetic and epidemiologic studies, the authors developed the Beth Israel Dystonia Screen (BIDS), a computer-assisted telephone interview. Objective: To evaluate the validity and utility of a computer-assisted telephone interview in screening for cervical dystonia. Methods: The BIDS was administered and videotaped neurologic examinations performed on 193 individuals from 16 families with cervical and cranial dystonia. With use of a final rating of definite dystonia, as determined by video review of a systematic neurologic evaluation, as the gold standard, the predictive value of a subset of questions from the BIDS was assessed. Results: A positive response to at least two of five screening questions had a sensitivity for cervical dystonia of 100% and a specificity of 92%. With use of a positive response to three or more questions, definite dystonia was determined with 81% sensitivity and 97% specificity. Conclusions: The Beth Israel Dystonia Screen (BIDS) identifies cervical dystonia with excellent sensitivity and specificity in a family-based sample. The authors recommend the BIDS for family studies, but cross-validation in a population sample is advisable before applying this method to epidemiologic studies.
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