RESUMEN
BACKGROUND/PURPOSE: Hereditary spastic paraplegias (HSPs) are clinically and genetically heterogeneous neurodegenerative disorders. Defects in the SPG4 and SPG3A genes are the two leading causes of HSPs with autosomal dominant inheritance (AD-HSPs). The purpose of this study was to investigate the clinical features and associated genetic mutations in Taiwanese families with AD-HSP. METHODS: Four kindreds with AD-HSP were recruited, and clinical data were collected from the affected individuals. Genetic studies were conducted in the following order: sequence analysis of the SPG4 gene (SPAST) exons, multiplex ligation-dependent probe amplification to detect genetic rearrangements in SPAST, and sequence analysis of the SPG3A gene exons. RESULTS: Four different SPAST mutations were detected, including a novel small deletion, a missense mutation, and two gross deletions involving exon 17. Although all symptomatic cases manifested as uncomplicated phenotypes, considerable intrakindred and interkindred variations in terms of age at onset, rate of progression, and severity of disease were observed. CONCLUSION: Mutation patterns and phenotypic expressivity are heterogeneous in Taiwanese patients with SPG4-related HSP. Genetic rearrangements could be a significant cause of SPG4-related HSP in the Taiwanese population. Assessment of the large deletions that could present in SPAST is warranted when direct sequencing is uninformative.
Asunto(s)
Paraplejía Espástica Hereditaria/genética , Adenosina Trifosfatasas/genética , Adolescente , Adulto , Edad de Inicio , Anciano , Niño , Progresión de la Enfermedad , Exones/genética , Familia , Femenino , Proteínas de Unión al GTP/genética , Eliminación de Gen , Genes Dominantes/genética , Humanos , Masculino , Proteínas de la Membrana/genética , Persona de Mediana Edad , Mutación Missense/genética , Fenotipo , Espastina , Taiwán , Adulto JovenRESUMEN
Dystonia is a diverse movement disorder characterized by involuntary muscle co-contraction of the agonist and antagonist, which may cause twisting and repetitive movements or abnormal posture. Dystonia is the least understood movement disorder associated with the basal ganglia dysfunction. While dysfunction of cortico-striatal-thalamo-cortical motor circuits is likely to play a fundamental role in the pathophysiology of dystonia, the disorder does not easily fit into the hypokinetic or the hyperkinetic category of basal ganglion diseases. There was evidence of widespread impairment of the inhibition involving multiple levels of the nervous system. There was also significant data to support the notion that the sensory function and sensorymotor integration were debit in patients with dystonia. The reciprocal inhibition curves between the forearm muscles were abnormal at the spinal cord level, as well as the blink reflex recovery curves at the brain stem level. The motor cortex excitability was enhanced while the transcranial magnetic stimulation. The dystonia showed decreased inhibition of the intracortical inhibition and facilitation and short cortical silent period. The pre-movement gating of the somatosensory evoked potentials and the somatosensory homunculus were abnormal in dystonia. This review provides an overview of the recent studies of the pathophysiology of dystonia, with an emphasis on the cortical plasticity. The possible beneficial effects of the transcranial magnetic stimulation (TMS) and repetitive transcranial magnetic stimulation (rTMS) with new paradigm are also discussed.