遗传性痉挛性截瘫伴薄胼胝体6例报道并文献复习

目的探讨遗传性痉挛性截瘫伴薄胼胝体(HSP-TCC)的发病机制、临床特点、影像学表现及预后。方法分析6例HSP-TCC患者的临床及影像学表现,结合文献复习总结其临床特征。结果 6例患者均青少年起病,表现为痉挛步态,腱反射亢进,病理征阳性,2例有共济失调。患者均无感觉障碍及大小便障碍。全部患者头颅MRI显示胼胝体变薄。结论 HSP-TCC作为复杂型遗传性痉挛性截瘫(HSP)的一种,临床上以双下肢痉挛性截瘫和薄胼胝体为特征,发病机制尚不清楚,预后较差。     

遗传性痉挛性截瘫伴胼胝体发育不良的遗传学研究进展

遗传性痉挛性截瘫伴胼胝体发育不良（HSP-TCC）是复杂型HSP的一种,临床特点为进行性双下肢痉挛伴胼胝体发育不良,多儿童及青少年发病,常伴智能障碍。HSP-TCC具有高度的遗传异质性,病理提示皮质脊髓束变性。目前已发现至少19个疾病基因,主要包括：SPG1、SPG11、SPG15、SPG21、SPG35、SPG44、PG47、SPG54、SPG56等。该文就近年来有关该病的遗传学研究进展进行了综述,以期有助于该病的鉴别与诊断。     

遗传性痉挛性截瘫伴胼胝体发育不良的临床分析及文献回顾

目的:分析遗传性痉挛性截瘫伴胼胝体发育不良(HSP-TCC)的临床特点,以提高对此病的认识。方法:结合文献复习并报告1 例HSP-TCC患者的临床和影像学表现。结果:本例HSP-TCC的双亲为表兄妹婚配,临床以缓慢进行性痉挛性截瘫为主要表现,MRI 示胼胝体发育不良和脑室周围白质疏松,侧脑室对称轻度扩大;胸腰髓明显变细,但脊髓本身未见明显异常信号。结论:建议凡家族性痉挛性截瘫患者均应常规行MRI检查,以判定是否并有胼胝体发育不良,可提高本病的诊断率。     

中国遗传性痉挛性截瘫的临床特点

目的 明确我国腓骨肌萎缩症的临床特点。方法 总结国内文献中报道的７８个家族，３５４例２及我院３９个家族、８１列患者的临床资料。结果 男：女约为１．７７：１，家族史阳性率６２．４％，其中常显、常隐、Ｘ隐性遗传分别为４１、１３、２个家系，同一家族患者发病年龄具有很高相关性。发病年龄１个月￣５５岁，平均１０．６岁，其中１￣２０岁起病占７１．２％；剪刀样步态７９．１％、双下肢肌张力增高８２．３％、肌力下降     

遗传性痉挛性截瘫伴胼胝体发育不良六例的临床特征与maspardin基因突变分析

遗传性痉挛性截瘫伴胼胝体发育不良（hereditary spastic paraplegia with thin corpus callosum，HSP-TCC）是一种常染色体隐性（AR）遗传的复杂型HSP，临床极为罕见，青少年发病，表现为缓慢进展的痉挛性截瘫伴痴呆，晚期可出现肌萎缩、小脑及锥体外系症状等，头部磁共振成像（MRI）示胼胝体发育不良和脑萎缩，多见于日本。Mast综合征也是一种AR遗传的复杂型HSP，儿童或青少年发病，     

遗传性痉挛性截瘫

遗传性痉挛性截瘫 (HSPS) ,也称作Strumpell -Lorrain病 ,是一组罕见的以显著的临床及遗传异质性为特征的疾病。自 1883年被初次描述以来已发现了多种的临床形式。单纯型表现为反射活跃 ,Babinski征 ,双下肢的痉挛及运动缺损通常伴有弓行足 ,深感觉损害 ,括约肌障碍 ,有时有上肢辩距障碍。其他形式称为复杂型 ,指表现为一种或几种神经或神经外特征。现已弄清其他神经变性疾病也可存在与复杂型HSP相似的表现型 ,如成人Friedreich’s共济失调和肌萎缩性侧索硬化症 (ALS) ,故这些疾病的分类不仅要靠临床而且要依赖遗传模式 (常染色体显性…     

遗传性痉挛性截瘫诊断策略

遗传性痉挛性截瘫（hereditary spastic paraplegia,HSP）是一组具有高度临床和遗传异质性的神经退行性疾病,以下肢进行性痉挛为最主要的临床特点。在临床实践中,如何对该疾病进行诊断和鉴别诊断,进一步在种类繁多的致病基因中进行HSP分型诊断,具有一定挑战性。随着基因检测技术不断发展,一方面诸多新致病基因得到克隆或重新定位,另一方面如何合理利用遗传分析辅助鉴别诊断和分型诊断,需进一步规范基因检测技术的应用策略。本文对HSP的临床特点、基因分型、诊断与鉴别诊断等进行综述。     

遗传性痉挛性截瘫1个家系报告

遗传性痉挛性截瘫１个家系报告董海波韩漫夫布茂利遗传性痉挛性截瘫临床上较少见。我们遇见一个家系２代３人发病，仅以双下肢痉挛性瘫痪为首发症状，现报告如下。先证者Ⅲ１，男性，３５岁。１９９７年６月２７日入院。患者于１０年前开始出现跑步停止受限，身体向前倾斜...     

遗传性痉挛性截瘫

遗传性痉挛性截瘫是一种遗传性脊髓小脑变性疾病，主要表现为双下肢痉挛性截瘫。多为常染色体显性遣传，少数为常染色体隐性，极少Ｘ连锁隐性。目前已发现常显遗传ＨＳＰ基因位于１４ｑ１．２、２ｑ２１．２４和１５ｑ１１．１，常隐ＨＳＰ基因位于８号染色体，Ｘ隐ＨＳＰ位于Ｘｑ２８和Ｘｑ２１．３～２４。单纯型者仅表现为痉挛性截瘫，复杂型者可合并各种脊髓外损害。目前可采用安定、巴氯芬、妙纳等改善病人的肌痉挛。     

遗传性痉挛性截瘫的研究进展

遗传性痉挛性截瘫(HSP)是一组由于轴索变性,合并或不合并脱髓鞘和神经元脱失而造成的神经系统变性疾病。目前,其发病机制还不明确,临床表现具有高度临床及遗传异质性,且遗传方式多样,基因诊断复杂。该文主要对HSP的分型、临床表现、病理改变、发病机制、诊断及鉴别诊断和治疗方法的研究进展进行阐述,以利于该病的早期诊断与治疗。     

遗传性痉挛性截瘫的临床和遗传特点

目的：探讨遗传性痉挛性截瘫的临床和遗传特点。方法：对39个家系113例患者的临床资料进行回顾性分析。结果：男：女为1：1.17，发病年龄2-58岁，平均21.4岁，30例以前发病占81.7％。有家族史者占89.4％，多呈常染色体显性遗传。近亲结婚家系占28.2％。单纯型24例，复杂型89例。双下肢肌力下降占65.5％，肌张力增高和腱反射亢进均为96.5％，病理征阳性68.1％。合并症中共济失调占46.9％，肌萎缩占32.7％，痴呆占18.6％。结论：本组遗传性痉挛性截瘫患者多于青少年或青年发病，女性多于男性，复杂型较单纯型多见，遗传方式以常染色体显性遗传多见，近亲结婚明显增加该病的发生。     

Novel mutations c.[5121_5122insAG]+[6859C>T] of the SPG11 gene associated with cerebellum hypometabolism in a Chinese case of hereditary spastic paraplegia with thin corpus callosum

Hereditary spastic paraplegia (HSP) is a very heterogeneous disease, both genetically and clinically. To date, approximately 52 loci and 31 genes have been reported to be involved in the causality of HSP. The pattern of inheritance of the disease can be autosomal dominant, autosomal recessive, or X-linked recessive. Autosomal recessive HSP with thin corpus callosum (ARHSP-TCC) is one form of this disease, and a recessive gene, SPG11, is responsible for 41–77% of all ARHSP-TCC cases. SPG11 encodes the protein SPATACSIN, which is most prominently expressed in the cerebellum. However, little is known about its function. Despite diverse clinical presentations, diffuse hypometabolism in the cerebellum has not been reported previously. We have identified an HSP-TCC patient that presented with prominent intellectual disability rather than spasticity. ¹⁸Fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸FDG-PET/CT) examination showed diffuse hypometabolism in both cerebella. Mutation screening of the SPG11 gene using Sanger sequencing identified the novel compound heterozygous mutation c.[5121_5122insAG]+[6859C>T] (p.[I1708RfsX2]+[Q2287X]) in the patient. The mother bears the c.5121_5122insAG mutation, which results in a frameshift and is predicted to truncate the 735 amino acids from the C-terminus, and the father carries the c.6859C>T mutation, which terminates the 157 amino acids from the C-terminus. Therefore, these mutations may result in the loss of function of wild-type SPATACSIN. Our results suggest that SPATACSIN may be involved in cerebella metabolism, and the novel mutations provide more data for the mutational spectrum of this gene, which will aid in the development of quick and accurate genetic diagnostic tools for this disease.     

Neurological and neuroradiological progression in hereditary spastic paraplegia with a thin corpus callosum

We followed-up a Japanese man suffering from hereditary spastic paraplegia with a thin corpus callosum (HSP-TCC) by single photon emission computed tomography (SPECT) using 123IN-isopropyl-piodoamphetamine (123I-IMP) over 4 years (25 to 29 years old). Besides the initial symptoms of lower limb spasticity, mental deterioration slightly progressed and upper limb spasticity and slight cerebellar ataxia were developed, during the period. Cranial magnetic resonance imaging (MRI) revealed an extremely thin corpus callosum and medial frontal atrophy, which remained essentially unchanged during the period. 123I-IMP SPECT demonstrated that cerebral blood flow was decreased in the thalamus and the medial frontal, temporal and parietal cortices at the first examination, and that the thalamus showed further reduction but the other involved regions presented essentially no progression during the follow-up period. This is the first report referring to the longitudinal clinical and neuroradiological changes in HSP-TCC.     

Autopsy case of hereditary spastic paraplegia with thin corpus callosum showing severe gliosis in the cerebral white matter

We report an autopsy case of a 51‐year‐old man clinically diagnosed with a complicated type of hereditary spastic paraplegia. His sister showed similar manifestations. Gait disturbance was manifested at 14 years of age. Subsequently, slowly progressive spastic tetraplegia developed with mental deterioration, neuropathy and amyotrophy. Marked cerebral atrophy with thin corpus callosum was shown by cranial MRI. Autopsy revealed a severely atrophic brain with extreme thinning of the whole corpus callosum. Microscopically, neurodegeneration was found in the corticospinal tract, thalamus, cerebral white matter and substantia nigra, as well as in the anterior horn and posterior column of the spinal cord. The remaining neurons contained large amounts of lipofuscin and eosinophilic granules. Unique to this patient was the severe gliosis in the cerebral white matter and substantia nigra, suggesting that sufficient development had been established when the degenerative process occurred. The predominant feature of the present case is the neurodegeneration process rather than hypoplasia.     

Prospective neuroimaging study in hereditary spastic paraplegia with thin corpus callosum.

Our objective was to estimate the frequency as well as to establish the clinical and neuroimaging profile of hereditary spastic paraplegia with thin corpus callosum (HSP-TCC). HSP-TCC was recognized as a specific clinical subtype of HSP and mapped to chromosome (ch) 15q13-15 in Japanese families. It has been considered rare in western countries. We assessed 45 patients with autosomal recessive HSP from 20 different families in search of clinical and imaging criteria for the diagnosis of HSP-TCC. In addition, HSP-TCC patients underwent further neurological, imaging and genetic evaluation. MRI scans were performed in a 2T scanner and sagittal T1 weighted images used for semiautomated volumetric measurements of corpus callosum, cerebellum, and brain. In seven patients, a 2-year follow-up MRI scan was performed. We genotyped seven microsatellite markers flanking the 15q13-15 candidate region and calculated two-point and multipoint LOD scores (Z). We identified 13 patients from seven unrelated families with HSP-TCC. MRI showed significant corpus callosum, cerebral and cerebellar volumetric reductions (P<0.001, P=0.03, and P=0.01, respectively). In the prospective analysis, we found progressive corpus callosum atrophy (P=0.04). Two-point and multipoint LOD scores were significantly negative for markers genotyped on ch 15q. However, independent pedigree analysis did not yield significant results. HSP-TCC was found in 35% of families with autosomal recessive HSP. MRI volumetry showed cerebral and cerebellar atrophy in association with progressive corpus callosum thinning. Genetic studies did not show evidence for linkage to ch 15q.     

Hereditary spastic paraplegia with thin corpus callosum and cataract: a clinical description of two siblings

We report two siblings with autosomal recessive hereditary spastic paraplegia and thin corpus callosum. These patients had a similar history of progressive spastic gait, followed by mental impairment in the second decade. In addition to rigospasticity, ataxia, and foot deformity, both patients had congenital cataract on ophthalmologic examination. The association of cataract and thin corpus callosum suggests a distinct genetic disorder involving these structures in complicated spastic paraplegia.     

Autosomal recessive hereditary spastic paraplegia with thin corpus callosum: a novel mutation in the SPG11 gene and further evidence for genetic heterogeneity

Background and purpose:  Autosomal Recessive Hereditary Spastic Paraplegia with Thin Corpus Callosum (AR-HSPTCC) is a clinically and genetically heterogeneous complicated form of spastic paraplegia. Two AR-HSPTCC loci have been assigned to chromosome 15q13-15 ( SPG11 ) and chromosome 8p12-p11.21 respectively. Mutations in the SPG11 gene, encoding the spatacsin protein, have been found in the majority of SPG11 families. In this study, involvement of the SPG11 or 8p12-p11.21 loci was investigated in five Italian families, of which four consanguineous.
Methods:  Families were tested for linkage to the SPG11 or 8p12-p11.21 loci and the SPG11 gene was screened in all the affected individuals.
Results:  Linkage was excluded in the four consanguineous families. In the only SPG11 -linked family the same homozygous haplotype 4.2 cM across the SPG11 locus was shared by all the three affected siblings. A novel c.2608A>G mutation predicted to affect the splicing was found in exon 14 of the SPG11 gene.
Discussion:  This collection of families contributes to highlight the intra and inter locus heterogeneity in AR-HSPTCC, already remarked in previous reports. In particular, it confirms heterogeneity amongst Italian families and reports a new mutation predicted to affect splicing in the spatacsin gene.     

SPG11 spastic paraplegia

Autosomal recessive hereditary spastic paraplegia (AR HSP) with thin corpus callosum (TCC) is a rare neurodegenerative disorder often caused by mutations in the gene encoding for spatacsin at the SPG11 locus on chromosome 15q. The disease is characterized by progressive spastic paraparesis and mental retardation which occur during the first two decades of life and frequently with peripheral neuropathy. Brain magnetic resonance imaging (MRI) reveals typical TCC with periventricular white matter changes. We describe two patients, of Turkish descent, from the same consanguineous family and affected with SPG11 in association with unusual early-onset parkinsonism. Parkinsonism occurred during the very early stages of SPG11 in both patients, being in one the inaugural symptom of the disease presented as a resting tremor with akinesia, rigidity and expressing an initial moderate levodopa-response that progressively weakened. The second patient presented a resting tremor with mild akinesia and no levodopa-response. Both patients were affected with progressive spastic paraparesis which had initially occurred at 15 and 12 years of age, respectively, in association with mild mental retardation and an axonal polyneuropathy. TCC with periventricular white matter changes (PWMC) was evident by MRI and ¹²³I-ioflupane SPECT was abnormal. Genetic analysis detected for both patients a new c.704_705delAT, p.H235RfsX12 homozygous mutation in SPG11. This report provides evidence that parkinsonism may initiate SPG11-linked HSP TCC and that SPG11 may cause juvenile parkinsonism.