Wijemanne Subhashie, Shulman Joshua M, Jimenez-Shahed Joohi, Curry Daniel, Jankovic Joseph
Parkinson's Disease Center and Movement Disorders Clinic Department of Neurology Baylor College of Medicine Houston Texas USA.
Department of Molecular and Human Genetics Baylor College of Medicine Houston Texas USA.
Mov Disord Clin Pract. 2015 Apr 28;2(2):149-154. doi: 10.1002/mdc3.12144. eCollection 2015 Jun.
The aim of this study was to describe a case of hereditary spastic paraplegia (HSP) resulting from mutations, presenting with a complex phenotype of dopa-responsive dystonia (DRD), diagnosed using whole exome sequencing (WES). HSP resulting from typically presents with spasticity, cognitive impairment, and radiological evidence of thin corpus callosum. Initial presentation with DRD has not been previously reported on.
This 11-year-old boy with delay in fine motor skills, presented at 8 years of age with progressive, generalized dystonia with diurnal variation, bradykinesia, and stiff gait. There was marked improvement in dystonia with levodopa, but he soon developed wearing-off phenomenon and l-dopa-induced dyskinesia. Family history was unremarkable.
Brain MRI showed thinning of the anterior corpus callosum with periventricular white matter changes. I-ioflupane single-photon emission coupled tomography showed bilateral severe presynaptic dopamine deficiency. WES identified transheterozygous allelic variants in the on chromosome 15, including a truncating STOP mutation (p.E1630X) and a second heterozygous coding variant (p.L2300R). Dystonia improved with globus pallidus internus (GPi) DBS surgery.
HSP resulting from should be considered in the differential diagnosis of a patient presenting with DRD, parkinsonism, and spasticity. This case expands the HSP genotype and phenotype. GPi DBS may be a therapeutic option in selected patients.
本研究旨在描述一例由突变导致的遗传性痉挛性截瘫（HSP）病例，该病例表现为多巴反应性肌张力障碍（DRD）的复杂表型，通过全外显子组测序（WES）进行诊断。由[具体基因名称未给出]导致的HSP通常表现为痉挛、认知障碍以及胼胝体变薄的影像学证据。此前尚未有以DRD为初始表现的报道。
这名11岁的男孩精细运动技能发育迟缓，8岁时出现进行性全身性肌张力障碍，伴有日变化、运动迟缓及步态僵硬。左旋多巴治疗后肌张力障碍有明显改善，但他很快出现了疗效减退现象和左旋多巴诱发的运动障碍。家族史无异常。
脑部MRI显示胼胝体前部变薄，脑室周围白质改变。碘氟潘单光子发射计算机断层扫描显示双侧严重的突触前多巴胺缺乏。WES在15号染色体上的[具体基因名称未给出]中鉴定出反式杂合等位基因变异，包括一个截短的终止突变（p.E1630X）和另一个杂合编码变异（p.L2300R）。苍白球内侧核（GPi）深部脑刺激（DBS）手术使肌张力障碍得到改善。
在对表现为DRD、帕金森综合征和痉挛的患者进行鉴别诊断时，应考虑由[具体基因名称未给出]导致的HSP。该病例扩展了HSP的基因型和表型。GPi DBS可能是部分患者的一种治疗选择。
