Phenotypic overlap in familial and sporadic primary adult-onset extracranial dystonia

We recently demonstrated that familial and sporadic blepharospasms share several phenotypic features (including age of dystonia onset, sex, and tendency to spread) believed to reflect the etiology of a blepharospasm. To investigate whether familial and sporadic forms of primary adult-onset dystonia other than the blepharospasm also share phenotypic features, we studied the families of 98 probands with primary adult-onset dystonia other than blepharospasms using a validated two-step procedure (questionnaire and clinical examination) that yields 95?% sensitivity and 100?% specificity when used to identify dystonia among relatives. The 98 probands provided a population of 402 living first-degree relatives aged 20?years or more, 336 of whom (83?%, 111 parents, 152 siblings, and 73 children) were screened for dystonia. The screening procedure identified 26 affected relatives (five parents, 16 siblings, and five children; 11 men/15 women; age at dystonia onset, 51?±?11.7?years) from 24/98 families (25?%). No causes of secondary dystonia were found in the relatives who suffered from various forms of dystonia. When familial and sporadic patients were compared, no significant differences emerged in age, education, family size, sex distribution, age at dystonia onset, or tendency to spread. The phenotypic overlap we observed between the study groups suggests that familial and sporadic patients with primary adult-onset dystonia other than blepharospasm probably share a common etiological background.     

Phenotype of the DYT1 mutation in the TOR1A gene in a Polish population of patients with dystonia. A preliminary report

BACKGROUND AND PURPOSE: DYT1 dystonia is the most common form of inherited primary dystonia. The aim of the study was: 1) to evaluate the prevalence of the DYT1 mutation in a population of Polish patients with early-onset generalized dystonia and with other forms of familial dystonia, 2) to evaluate the frequency of the DYT1 mutation in patients with writer's cramp, 3) to characterize the phenotype of the DYT1 mutation in the Polish population, and 4) to define the group of patients in whom genetic testing is recommended. MATERIAL AND METHODS: The following groups of patients were included in the study: 1) patients with early-onset (<30 years) generalized dystonia and those patients with onset after age 30 years who have relatives with early-onset dystonia, 2) patients with writer's cramp (focal or as part of segmental dystonia) independently of age of onset, 3) asymptomatic (adult only) relatives of the diagnosed DYT1 carriers. Genetic tests were performed in 63 subjects---28 sporadic cases of dystonia, 20 patients with familial dystonia, and 15 asymptomatic relatives of patients with confirmed DYT1 mutation. RESULTS: The DYT1 mutation was found in 17 subjects--10 patients with dystonia and 7 asymptomatic relatives (from 6 families). In all mutation carriers dystonia occurred in one limb before age 26 years. In 8 patients, generalization of dystonia was observed and in 2 cases it remained in a focal form. CONCLUSIONS: 1. The prevalence of DYT1 mutation among patients with early-onset (相似文献   

Epidemiology of primary blepharospasm.

We review epidemiological data on primary blepharospasm (BSP). There is a large variation in the stated prevalence of BSP, with crude estimates ranging from 16 to 133 per million in different studies. A large proportion of this variability may be the result of differences in physician education on BSP. Age and female gender may increase the risk of developing BSP. The few case-control studies focusing on adult dystonias including BSP showed an increased risk in association with family history of dystonia and/or postural tremor, prior head and face trauma, and prior eye disease (e.g., blepharitis and keratoconjunctivitis), and a decreased risk associated with cigarette smoking. No association was found with age-related medical conditions such as hypertension and diabetes, family history of parkinsonism, and a history of anxiety or depression. Broocks et al. [Am J Psychiatry, 1998;155:555-557] found a significantly higher frequency of obsessive-compulsive symptoms in BSP than hemifacial spasm despite the clinical similarity. Among putative risk factors for BSP, age at onset, female gender, and prior head or face trauma may affect spread of dystonia to adjacent body regions. While limited, the body of epidemiological data support the idea that environmental and familial, possibly genetic, factors may both be important in the etiology of BSP.     

Frequency of familial inheritance among 488 index patients with idiopathic focal dystonia and clinical variability in a large family

Idiopathic torsion dystonia is characterized by involuntary twisting movements and postures. One molecularly defined form with generalized dystonia has been shown to be autosomal dominantly inherited with reduced penetrance in chromosome 9q34.1, especially in Ashkenazi Jewish families, while other generalized families from Europe and families with other subtypes of dystonia have been excluded from linkage to this locus. Genealogical studies suggest that the much more frequent focal dystonia follows an autosomal dominant inheritance with reduced penetrance as well. For our study, 488 patients with focal dystonia, without a tendency for generalization, were interviewed for their family history. Evidence for hereditary disposition was found in 88 individuals. In a second step, all available family members of 17 of the 488 index patients (chosen for cooperation) were clinically examined. Objective diagnosis of affected relatives was established in 13 families, whereas only 4 of the 17 index patients had previously admitted a positive family history. Furthermore, a large threegeneration family with focal dystonia linked to chromosome 18p (linkage data described elsewhere) was identified. The familial pattern of all reported families is compatible with autosomal dominant inheritance with reduced penetrance. Assessment only on patients' report leads to underestimation of the frequency of familial idiopathic focal dystonia.     

Focal and segmental primary dystonia in north-western Germany--a clinico-genetic study

OBJECTIVES: To determine the frequency of familial focal and segmental dystonias in a large patient cohort with primary dystonia from north-western Germany. MATERIALS AND METHODS: In this study, 130 patients with focal or segmental dystonia were examined and a family history was obtained. Whenever possible, affected relatives were examined (a total of 789 first-degree relatives). Data on disease duration, age at disease onset and age of the patients were investigated by Student's t-test and a segregation analysis was performed by Weinberg's proband method. RESULTS: Age at onset of disease was significantly later in the blepharospasm group. Only in the writer's cramp group were women outnumbered by men. A positive family history was found in 15 of the 130 index patients (11.5%). None of 102 index patients tested carried the GAG deletion in the DYT1 gene. CONCLUSIONS: In accordance with previous series our study provides evidence that primary focal dystonia may have a genetic etiology, most probably caused by an autosomal dominant trait with reduced penetrance.     

Quality of sleep in primary focal dystonia: a case–control study

Background: Sleep disturbances are common in patients with movement disorders. Evaluating quality of sleep is of primary importance because of the effect that nocturnal and daytime sleep abnormalities exert on general health status. However, quality of sleep has never been addressed in detail in patients with dystonia. The aim of this case–control study was to analyse quality of sleep in patients with the two most common forms of primary focal dystonia, blepharospasm (BSP) and cervical dystonia (CD). Methods: We evaluated quality of sleep (Pittsburgh Sleep Quality Index, PSQI) and excessive daytime sleepiness (Epworth Sleepiness Scale, ESS) in 98 patients with focal adult‐onset dystonia (52 with BSP; 46 with CD) and in a group of 56 age‐and gender‐matched healthy subjects. The Beck Depression Inventory (BDI) was used for the evaluation of depressive symptomatology. Results: Quality of sleep was impaired (significantly higher PSQI scores) in both groups of patients. However, differences in PSQI scores between patients with CD and control subjects were partly confounded by BDI scores, whereas differences in PSQI scores between patients with BSP and control subjects were not influenced by BDI. Excessive daytime sleepiness was not significantly more frequent than in control subjects in either patients with BSP or patients with CD. Conclusions: This study suggests that the assessment and treatment of insomnia‐related complaints should be considered in global management plans of patients with focal dystonia, particularly in those affected by BSP.     

The phenomenology of the geste antagoniste in primary blepharospasm and cervical dystonia

The geste antagoniste (GA), a relatively common feature of adult‐onset primary dystonia, has been systematically evaluated only in cervical dystonia, but it is still unclear whether its frequency and phenomenology differ among the various forms of focal dystonia. We analysed the frequency, phenomenology, effectiveness, and relationship of the GA with demographic/clinical features of dystonia in a representative clinical series of patients with the two most common forms of adult‐onset primary dystonia, blepharospasm (BSP) and cervical dystonia (CD). Clinical data were gathered using a standardized questionnaire, which showed substantial test‐retest reliability (κ = 0.79, P < 0.00001). The frequency of GA was similar among patients with BSP (42/59, 71.2%) and patients with CD (27/32, 84.4%), and in both groups GA showed similar effectiveness in reducing dystonia. The repertoire of GA was heterogenous in both BSP and CD patients, in whom seven BSP‐related and five CD‐related types of GA were recorded, and a “forcible” type of GA was present in 69% of BSP patients and in 48.1% of CD patients. In our whole patient population, age at dystonia onset was significantly lower among patients reporting a GA compared to those without GA (P = 0.01). GA features shared by BSP and CD predominate over differences, suggesting common mechanisms underlying this phenomenon in the two forms of primary adult‐onset dystonia. © 2010 Movement Disorder Society     

Temporal discrimination,a cervical dystonia endophenotype: Penetrance and functional correlates

The pathogenesis of adult‐onset primary dystonia remains poorly understood. There is variable age‐related and gender‐related expression of the phenotype, the commonest of which is cervical dystonia. Endophenotypes may provide insight into underlying genetic and pathophysiological mechanisms of dystonia. The temporal discrimination threshold (TDT)—the shortest time interval at which two separate stimuli can be detected as being asynchronous—is abnormal both in patients with cervical dystonia and in their unaffected first‐degree relatives. Functional magnetic resonance imaging (fMRI) studies have shown that putaminal activation positively correlates with the ease of temporal discrimination between two stimuli in healthy individuals. We hypothesized that abnormal temporal discrimination would exhibit similar age‐related and gender‐related penetrance as cervical dystonia and that unaffected relatives with an abnormal TDT would have reduced putaminal activation during a temporal discrimination task. TDTs were examined in a group of 192 healthy controls and in 158 unaffected first‐degree relatives of 84 patients with cervical dystonia. In 24 unaffected first‐degree relatives, fMRI scanning was performed during a temporal discrimination task. The prevalence of abnormal TDTs in unaffected female relatives reached 50% after age 48 years; whereas, in male relatives, penetrance of the endophenotype was reduced. By fMRI, relatives who had abnormal TDTs, compared with relatives who had normal TDTs, had significantly less activation in the putamina and in the middle frontal and precentral gyri. Only the degree of reduction of putaminal activity correlated significantly with worsening of temporal discrimination. These findings further support abnormal temporal discrimination as an endophenotype of cervical dystonia involving disordered basal ganglia circuits. © 2014 International Parkinson and Movement Disorder Society     

Is there familial transmission of pedophilia?

A naturalistic, double-blind, family history comparison of sexual deviancy in the first degree relatives of inpatients with pedophilia and nonpedophilic paraphilia was done. Both proband groups were similar in demographic characteristics, except that pedophiles had a later onset of illness and were older during hospitalization. All patients were men. Sexual deviancy was found in 18.5 per cent of the families of paraphiliacs; only 3 per cent of a psychiatric control group had a family member with sexual deviancy. The preponderance of affected relatives were men. The types of sexual deviancy found in the families of the groups differed. Sexual deviancy among the pedophiles' families consisted of pedophilia. In families of nonpedophilic paraphiliacs, sexual deviancy was predominantly a paraphilia not involving children. These data suggest that pedophilia is familial; however, further studies are needed to delineate the manner of transmission. Nonetheless, pedophilia is found more frequently in families of pedophiles than in families of nonpedophilic paraphiliacs. This indicates specificity in the familial transmission. Thus pedophilia may be independent of the other paraphilias.     

Heritability of cluster headache

We conducted a pedigree analysis in 222 patients with cluster headaches (CHs) in order to assess a familial predisposition to the disease. Heritability was determined by Falconer's index (from the incidence of CH among first degree relatives of probands compared with a control population), which varies between 0 and 1 (none or full genetic causation). A positive family history (I/II degree relatives) was found in 2.3% of our CH patients. Three generations were affected in one family and two generations in another two families. The calculated Falconer's heritability index was, however, only 0.26 ± 0.25 SD. Our study confirms a higher familial occurrence of CH, some families showing a pattern compatible with autosomal dominant inheritance with reduced penetrance. The low Falconer's index indicates, however, a large non-genetic causation in most cases of CH.