Analysis of DYT1 and DYT6 in Thai patients with primary dystonia

@# DYT1 and DYT6 dystonias are the two most common genetic primary dystonias. However, they are rare in the Asian population and have never been reported in Thailand. DYT6 dystonia typically presents with craniosegmental dystonia with speech involvement, whereas DYT1 dystonia typically presents with lower limb dystonia, which tends to become generalized over time. Methods: Blood samples were collected from 14 patients with primary dystonia evaluated in five tertiary hospitals in Thailand. Genotyping of the TOR1A and THAP1 gene was performed. Results: Two patients were found to have a missense mutation, p.M143V (c.427A>G), in exon 3 of the THAP1 gene confirming the diagnosis of DYT6 dystonia. One patient was a woman who developed blepharospasm and lower cranial dystonia at the age of 38 years. Her dystonia spread to the neck and arm six months later. The other patient developed focal hand dystonia at the age of 34 years. The TOR1A mutation was not identified in any of these 14 patients.

Genetic evaluation for TOR1-A (DYT1) in Brazilian patients with dystonia / Avaliação genética para TOR1-A (DYT1) em pacientes brasileiros com distonia

Several genes have been mapped in families or in sporadic cases of dystonia. TOR1-A (DYT1) gene was linked to isolated dystonia. Objective To associate clinical information of patients with dystonia with the TOR1-A gene mutations. Method Eighty-eight patients with dystonia in cervical area (focal, segmental, multifocal and generalized) were recruited at Movement Disorders Clinic of Hospital de Clínicas of the Federal University of Paraná between June of 2008 and June of 2009. They were submitted to the clinical evaluation. DNA was extract from blood and submitted at analysis to TOR1-A mutations by PCR according standard protocols. Results Two patients had c.907GAGdel mutation on TOR1-A gene. These patients, with familial history of dystonia, started his symptoms by legs and had secondary generalization. Conclusion We can suggest that analysis for TOR1-A mutations should be performed only in patients with early onset, generalized and familial dystonia. .

Tem sido mapeada uma série de genes em pacientes com distonia. O gene TOR1-A (DYT1) foi associado a casos de distonia primária. Objetivo Associar os achados clínicos dos pacientes com distonia com mutações em TOR1-A. Método Foram selecionados 88 pacientes com distonia na região cervical (focal, segmentar, multifocal e generalizada) no Setor de Distúrbios do Movimento do Hospital de Clínicas da Universidade Federal do Paraná entre junho de 2008 e junho de 2009. Esses pacientes foram submetidos à avaliação clínica. O DNA foi extraído do sangue periférico e submetido à análise para mutações em TOR1-A através de protocolos padronizados. Resultados A mutação c.907GAGdel foi encontrada em duas pacientes. Ambas tinham história familiar de distonia e iniciaram seus sintomas pelos membros inferiores, evoluindo com generalização. Conclusão Podemos sugerir que a análise para mutações em TOR1-A deve ser realizada em pacientes com distonia de inicio precoce, história familiar e generalização. .

Cervical dystonia: about familial and sporadic cases in 88 patients / Distonia cervical: consideracoes sobre casos esporadicos e familiares em 88 pacientes

Cervical dystonia (CD) affects the musculature of the neck in a focal way or associated to other parts of the body. The aim of this study was to identify clinical differences between patients with dystonia patients without family history and with family history (sporadic). Eighty-eight patients with CD were recruited in a Movement Disorders Clinic between June of 2008 and June of 2009. Only patients with no etiological diagnosis were accepted for analysis. The age of onset of symptoms was later in patients with focal and segmental dystonia than in patients with generalized dystonia (p<0.001). The severity of symptoms was higher in patients with sporadic dystonia than in familial patients (p<0.01). Generalized cases were more severe in patients with a family history (p<0.01). Sporadic patients had higher levels of pain than familial cases (p<0.05). We expect soon to present the results of genetic analyzes of these patients.

A distonia cervical (CD) afeta a musculatura do pescoço de modo focal ou em combinação com outras partes do corpo. O objetivo deste estudo foi identificar diferenças clínicas entre pacientes com distonia com história familiar e pacientes sem história familiar (esporádicos). Foram selecionados 88 pacientes com DC no Setor de Distúrbios do Movimento entre julho de 2008 e junho de 2009. Somente os pacientes sem diagnóstico etiológico foram admitidos para análise. A idade de início dos sintomas foi mais tardia em pacientes com distonia focal e segmentar do que em pacientes com distonia generalizada (p<0,001). A gravidade dos sintomas foi maior em pacientes com distonia focal esporádicos do que naqueles com história familiar (p<0,01). Os casos generalizados foram mais graves nos pacientes com história familiar (p<0,01). Pacientes esporádicos tiveram níveis maiores de dor em relação aos casos familiares (p<0,05). Esperamos apresentar em breve resultados de análises genéticas desses pacientes.

Deep Brain Stimulation of the Globus Pallidus in a 7-Year-Old Girl with DYT1 Generalized Dystonia

The experience of pediatric deep brain stimulation (DBS) of the globus pallidus internus (GPi) in the treatment of early-onset DYT1 generalized dystonia is still limited. Here, we report the surgical experience of bilateral GPi-DBS under general anesthesia by using microelectrode recording in a 7-year-old girl with early-onset DYT1 generalized dystonia. Excellent improvement of her dystonia without neurological complications was achieved. This case report demonstrates that GPi-DBS is an effective and safe method for the treatment of medically refractory early-onset DYT1 generalized dystonia in children.

Clinical View Points on Primary Dystonia and Dystonia-plus Syndrome

Dystonia is a disorder of movement caused by involuntary, sustained muscle contractions affecting one or more sites of body, frequently causing twisting and repetitive movements, or postures. Dystonic movements and postures can produce a wide range of clinical presentations. Some distinguishing clinical features of dystonia can help the appropriate diagnosis of primary dystonia. The direction of contraction is almost consistent. Action dystonia and occupational dystonia are related to a movement or task-specific movement, respectively. Sensory tricks or gestes antagonistes are usually seen in patients with dystonia. Two types of tremors can be seen in patients with dystonia: a postural and/or action tremor that resembles essential tremor and a rhythmic expression of dystonic tremor. Sometimes dystonic tremor appears to be less regular and can be associated with myoclonus. Onset age of dystonia, body distribution and etiologies are important to correct diagnosis of primary dystonia. It is well known that the age of onset has important prognostic implications. This article highlights general concepts of phenomenology, classification that are relevant for the purpose a clinical diagnosis.

The DYT1 Gene Mutation in Primary Torsion Dystonia without Familial Background

BACKGROUND: The DYT1 dystonia is primary torsion dystonia (PTD) caused by a GAG deletion in DYT1 gene on chromosome 9 and transmits as autosomal dominant trait. It usually begins as limb-onset dystonia in childhood and tends to spread to other sites and has been reported as the most common cause of early onset PTD in Ashkenazi Jews. However, the frequency of DYT1 mutation in Korean patients with sporadic PTD has not been reported. METHODS: We examined dystonia patients who visited the Neurologic Clinic of Asan Medical Center between Jan 2001 and March 2002. The sporadic PTD patients of them were screened by genotyping with their peripheral blood samples. RESULTS: The 66 patients with sporadic PTD were recruited and two of them showed DYT1 mutation on Chromosome 9. One patient had segmental dystonia with cervical onset; the other had generalized dystonia with left leg onset. None of the patients with focal dystonia showed a DYT1 mutation. CONCLUSIONS: The DYT1 dystonia comprise a small portion of PTD without familial history in Korea. The DYT1 gene test should be considered in the early-onset or spreading type dystonia despite the absence of familial background in primary dystonia patient.

Familial Writer's Cramp with DYT1 Mutation: A Clinical and Genetic Analysis of a New Kindred

BACKGROUND: Recently a non-Jewish German family with writer's cramp was reported to have DYT1 mutation, expanding the phenotypic spectrum of DYT1. Although functional brain surgery has been tried for generalized dystonia, surgical outcome in focal dystonia patients with DYT1 mutation has not yet been reported. We investigated the clinical features and response to thalamotomy in familial writer's cramp with DYT1 mutation. METHODS: Family members were examined and clinically affected cases were video-taped. For the detection of DYT1 mutation, PCR-RFLP(restriction fragment length polymorphism) and heteroduplex analyses were performed as screening tests. Additional DNA sequencing was performed for the proband case to confirm the GAG deletion. RESULTS: Among this clinically homogeneous non-Jewish Korean family, five members in three generations were affected. Age of onset ranged from 7 to 20 years. Writing difficulty was the initial and the main disabling problem for all the affected individuals. All had the bilateral writer's cramp in succession. Dystonia remained focal and task-specific for the entire period after onset. Unilateral thalamotomy was performed in three patients, with remarkable improvement. Surgical benefit remained unchanged during the follow-up period of 6-8 years. DYT1 mutation cosegregated with the affected members. CONCLUSIONS: This study adds another evidence that DYT1 phenotype can present with purely focal and task-specific dystonia in all the affected members of a family. Marked and sustained improvement following thalamotomy in three of our patients suggests that stereotaxic thalamotomy is beneficial in familial focal dystonia with DYT1 mutation. (J Korean Neurol Assoc 19(2):110~115, 2001)

Familial Writer's Cramp with DYT1 Mutation: A Clinical and Genetic Analysis of a New Kindred

BACKGROUND: Recently a non-Jewish German family with writer's cramp was reported to have DYT1 mutation, expanding the phenotypic spectrum of DYT1. Although functional brain surgery has been tried for generalized dystonia, surgical outcome in focal dystonia patients with DYT1 mutation has not yet been reported. We investigated the clinical features and response to thalamotomy in familial writer's cramp with DYT1 mutation. METHODS: Family members were examined and clinically affected cases were video-taped. For the detection of DYT1 mutation, PCR-RFLP(restriction fragment length polymorphism) and heteroduplex analyses were performed as screening tests. Additional DNA sequencing was performed for the proband case to confirm the GAG deletion. RESULTS: Among this clinically homogeneous non-Jewish Korean family, five members in three generations were affected. Age of onset ranged from 7 to 20 years. Writing difficulty was the initial and the main disabling problem for all the affected individuals. All had the bilateral writer's cramp in succession. Dystonia remained focal and task-specific for the entire period after onset. Unilateral thalamotomy was performed in three patients, with remarkable improvement. Surgical benefit remained unchanged during the follow-up period of 6-8 years. DYT1 mutation cosegregated with the affected members. CONCLUSIONS: This study adds another evidence that DYT1 phenotype can present with purely focal and task-specific dystonia in all the affected members of a family. Marked and sustained improvement following thalamotomy in three of our patients suggests that stereotaxic thalamotomy is beneficial in familial focal dystonia with DYT1 mutation. (J Korean Neurol Assoc 19(2):110~115, 2001)