CAJ | 학술논문

目的探讨我国遗传性痉挛性截瘫(HSP)患者的临床与遗传学特点.方法对179例中国汉族人群HSP患者的临床资料和遗传学特点进行回顾性分析.结果共收集78个家系114例患者和65例散发患者,家族史阳性率为54.5%,未发现遗传早现现象,部分家系存在外显不全.患者中男女比例为1.84:1,平均发病年龄(18.1±14.0)岁,平均病程(12.3±11.5)年;常染色体显性遗传(AD)-HSP患者的发病年龄[(19.7±14.0)岁]较常染色体隐性遗传(AR)-HSP者[(14.5±8.8)岁]大(t=2.196,P＜0.05),病程较AR-HSP者长[分别为(17.9±14.4)年和(8.0±5.8)年,t=4.404,P＜0.01].单纯型79例,复杂型100例;AD-HSP以单纯型为主,AR-HSP以复杂型为主,两者构成比差异有统计学意义(F=19.322,P＜0.01).患者多以双下肢僵硬、不灵活起病,最常见的体征为双下肢腱反射亢进、肌张力增高和病理征阳性,其次为踝阵挛(46.9%)、双下肢肌力下降(42.5%)、足部畸形(30.7%)等;AR-HSP患者共济失调、构音障碍、智能减退和足部畸形较AD-HSP多见,泌尿系统症状较AD-HSP少见(P＜0.05).65例患者行颅脑MRI检查,发现胼胝体发育不良13例(20.0%)、小脑萎缩9例(13.8%);45例患者行脊髓MRI检查,发现脊髓变细7例(15.6%).结论本组HSP患者多于青少年期起病,男性多于女性.AD-HSP发病晚、病程长,以单纯型为主,更易出现泌尿系统症状;AR-HSP发病早、病程相对短,以复杂型多见,多伴有共济失调、构音障碍及智能减退,影像学改变以胼胝体发育不良多见;该病存在与性别相关的临床异质性,存在"女性保护"现象.
목적 탐토아국유전성경련성절탄(HSP)환자적림상여유전학특점.방법 대179례중국한족인군HSP환자적림상자료화유전학특점진행회고성분석.결과 공수집78개가계114례환자화65례산발환자,가족사양성솔위54.5%,미발현유전조현현상,부분가계존재외현불전.환자중남녀비례위1.84:1,평균발병년령(18.1±14.0)세,평균병정(12.3±11.5)년;상염색체현성유전(AD)-HSP환자적발병년령[(19.7±14.0)세]교상염색체은성유전(AR)-HSP자[(14.5±8.8)세]대(t=2.196,P＜0.05),병정교AR-HSP자장[분별위(17.9±14.4)년화(8.0±5.8)년,t=4.404,P＜0.01].단순형79례,복잡형100례;AD-HSP이단순형위주,AR-HSP이복잡형위주,량자구성비차이유통계학의의(F=19.322,P＜0.01).환자다이쌍하지강경、불령활기병,최상견적체정위쌍하지건반사항진、기장력증고화병리정양성,기차위과진련(46.9%)、쌍하지기력하강(42.5%)、족부기형(30.7%)등;AR-HSP환자공제실조、구음장애、지능감퇴화족부기형교AD-HSP다견,비뇨계통증상교AD-HSP소견(P＜0.05).65례환자행로뇌MRI검사,발현변지체발육불량13례(20.0%)、소뇌위축9례(13.8%);45례환자행척수MRI검사,발현척수변세7례(15.6%).결론 본조HSP환자다우청소년기기병,남성다우녀성.AD-HSP발병만、병정장,이단순형위주,경역출현비뇨계통증상;AR-HSP발병조、병정상대단,이복잡형다견,다반유공제실조、구음장애급지능감퇴,영상학개변이변지체발육불량다견;해병존재여성별상관적림상이질성,존재"녀성보호"현상.
Objective To investigate clinical and genetic characteristics of Chinese patients with hereditary spastic paraplegia (HSP).Methods To perform retrospective analyses of clinical data from 179 HSP Han Chinese patients from Xiangya Hospital and National Laboratory of Medical Genetics of China.Results The 179 patients comprised of 114 familial cases (from 41 families with AD inheritance and 37 families with AR inheritance ) and 65 sporadic cases.Genetic anticipation was not found, and nonpenetrance was observed in some HSP families.Male to female ratio was 1.84 to 1.The mean age of onset was ( 18.1 ± 14.0) years, and the mcan duration of disease was ( 12.3 ± 11.5) years.AD-HSP patients had an older age of onset ( ( 19.7 ± 14.0) years) and a longer duration ( ( 17.9 ± 14.4) years) than ARHSP patients (t =2.196 and 4.404, P value were less than 0.05 and 0.01 respectively).Most AD patients manifested as "pure" form, while "complicated" form occurred more frequently in AR patients (F =19.322, P ＜ 0.01 ).Leg stiffness and clumsiness were often the early symptoms at the beginning of the disease, and the most common leg signs were hypertonia, hyperreflexia and pathological reflexes.Other signs included ankle clonus (46.9% ), weakness (42.5% ) and deformities (30.7% ).Ataxia, dysarthria,mental retardation, and foot deformity were more frequently seen in AR-HSP patients than AD-HSP patients,but the frequency of urinary symptoms was higher in AD-HSP patients.Among 65 patients with MRI examination of the head, 13 cases and 9 cases showed corpus callosal dysplasia and cerebellar atrophy,respectively.In addition, spinal cord atrophy was found in 7 of 45 patients undergone MRI examination of the spine.Conclusions Adolescent onset of HSP is common, and more males than females are affected.When compared with AR-HSP, AD-HSP patients have an older age of onset, a longer duration, and more marked urinary symptoms.Most AD-HSP cases are of "pure" form, while most AR-HSP cases manifest as "complicated" form with ataxia, dysarthria, and mental retardation.Dysplasia of corpus callosum is commonly seen in AR-HSP individuals than AD-HSP.HSP manifest gender-related clinical heterogeneity,illustrating the phenomenon of "female protection".