遺傳性壓力易感性課件

1、遺傳性壓力易感性遺傳性壓力易感性遺傳性運(yùn)動感覺神經(jīng)病分類Charcot-Marie-Tooth neuropathiesCharcot-Marie-Tooth Type 1 (HMSNI) 疾病 遺傳方式 染色體定位 基因CMT1A AD 17p11.2-12 PMP22CMT1B AD 1q21.2-23 P0CMT1C AD unknown unknown遺傳性運(yùn)動感覺神經(jīng)病分類Charcot-Marie-TooCharcot-Marie-Tooth Type 2 (HMSNII) 疾病 遺傳方式 染色體定位 基因CMT2A AD 1p36 unknownCMT2B AD 3q13-22

2、unknown CMT2C AD unknown unknownCMT2D AD 7p14 unknownCharcot-Marie-Tooth Type 2 (HMDejerine-Sottas Disease (HMSNIII)疾病 遺傳方式 染色體定位 基因DSDA AD (AR?) 17p11.2-12 PMP22 DSDB AD (AR?) 1q21.2-23 P0Refsum Disease（HMSNIV）CMT4A AR 8q13-21.1 unknown CMT4B AR 11q23 unknown X-linked Charcot-Marie-ToothCMTX X-link

3、ed Xq13.1 Connexin32Dejerine-Sottas Disease (HMSNIHereditary Neuropathy with Pressure Palsies疾病 遺傳方式 染色體定位 基因HNPPA AD 17p11.2-12 PMP22HNPPB AD unknown unknownHereditary Neuropathy with PreCMT 遺傳神經(jīng)病比率 類型 CMT比率 CMT1 50 CMT2 2040？ CMT4 罕見 CMTX 1020 HNPP 少見CMT 遺傳神經(jīng)病比率 類型 名詞解釋PMP-22：周圍神經(jīng)髓鞘蛋白22 (periphera

4、l myelin protein 22)P0：髓鞘蛋白0Connexin32：髓鞘蛋白名詞解釋PMP-22：周圍神經(jīng)髓鞘蛋白22 (periphe遺傳學(xué)染色體17p11.2基因突變常見突變：85為DNA缺失染色體上缺失區(qū)包含PMP22基因缺失區(qū)與CMT1A基因重復(fù)區(qū)一致遺傳學(xué)染色體17p11.2基因突變點(diǎn)突變：8種點(diǎn)突變類型無義突變：終止密碼子G183A,G372A移碼突變：成熟前終止 (19-20delAG, 434delT); 長轉(zhuǎn)錄本 281-282insG 剪切點(diǎn)突變：78+1GT; 179+1GC 錯義突變：G88A (Val30Met) 突變造成PMP22蛋白失去功能點(diǎn)突變：8種點(diǎn)

5、突變臨床遺傳學(xué)聯(lián)系突變外顯率多樣性；37有基因缺失的病人沒有家族史；“ 散發(fā)”病人的雙親常存在基因缺失；1630具有HNPP表型的家族沒有PMP22基因缺失一些為PMP22點(diǎn)突變一些為基因插入一些PMP22基因缺失病人表現(xiàn)為慢性脫髓鞘神經(jīng)病，類似CMT1A臨床遺傳學(xué)聯(lián)系突變外顯率多樣性；臨床表現(xiàn)864歲均可發(fā)病，平均發(fā)病年齡26歲，一些病人無癥狀；一些基因突變攜帶者可無癥狀。麻痹神經(jīng)定位：腓神經(jīng)、尺神經(jīng)和臂叢神經(jīng)最常受累；正中神經(jīng)和橈神經(jīng)較常見；數(shù)根神經(jīng)可同時受累其他神經(jīng)包括顱神經(jīng)很少受累。臨床表現(xiàn)864歲均可發(fā)病，平均發(fā)病年齡26歲，一些病人無癥神經(jīng)麻痹發(fā)病特點(diǎn)：急性、復(fù)發(fā)緩解性周圍神經(jīng)麻痹

6、；神經(jīng)麻痹發(fā)病次數(shù)不一；受累神經(jīng)：110根；誘發(fā)因素：40在輕微外傷或肢體受壓后；局部重復(fù)活動功能恢復(fù)數(shù)天至數(shù)月50完全恢復(fù)9長期嚴(yán)重運(yùn)動障礙神經(jīng)麻痹發(fā)病特點(diǎn)：周圍神經(jīng)病表現(xiàn)常為不對稱性；常表現(xiàn)為運(yùn)動感覺喪失；反射：踝反射一般消失，其他腱反射可正常、減低或消失；骨骼：一些病人可有弓形足或脊柱側(cè)彎既往受累神經(jīng)支配的區(qū)域可見肌無力和萎縮周圍神經(jīng)病表現(xiàn)常為不對稱性；臂叢神經(jīng)麻痹Erb-Duchenne麻痹Dejerine-Klumpke麻痹神經(jīng)痛性肌萎縮臂叢神經(jīng)麻痹Erb-Duchenne麻痹臂叢神經(jīng)麻痹臂叢上部麻痹(Erb-Duchenne型)C5,C6神經(jīng)根支配的肌肉輕癱和萎縮(三角肌,肱二頭肌

7、,肱橈肌,橈肌,有時包括岡上肌,岡下肌和肩胛下肌)。產(chǎn)生特征性“ Porters tip”姿勢(上肢內(nèi)旋內(nèi)收,前臂伸直,手掌向外向后);肱二頭肌和肱橈肌反射減低或消失;三角肌區(qū)可有感覺障礙臂叢神經(jīng)麻痹臂叢上部麻痹(Erb-Duchenne型)臂叢下部麻痹C8和T1神經(jīng)根支配的肌肉輕癱,可有肌萎縮(如手腕和手指屈曲無力,手小肌肉無力,形成“ 爪形手”畸形)；手指屈肌反射減低或消失；上臂和前臂內(nèi)側(cè)、手尺側(cè)感覺可正?；蛳瑐?cè)Horner綜合癥伴T1神經(jīng)根受損。臂叢下部麻痹神經(jīng)痛性肌萎縮(Parsonage-Turner綜合癥)特征:急性劇烈的肩痛,放射至臂部、頸部和背部。在疼痛后數(shù)小時至數(shù)天內(nèi)出現(xiàn)

8、肩部和鄰近肌肉麻痹。疼痛常在數(shù)天內(nèi)消失。神經(jīng)痛性肌萎縮(Parsonage-Turner綜合癥)尺神經(jīng)麻痹手指夾攏困難，小指呈外展位，第4，5指不能伸直而呈屈曲位感覺障礙：小指和環(huán)指尺側(cè)及尺側(cè)半手背尺神經(jīng)麻痹手指夾攏困難，小指呈外展位，第4，5指不能伸直而呈橈神經(jīng)麻痹伸腕、伸指及伸拇肌癱瘓（垂腕征）手背的拇指和第1、2掌骨間隙區(qū)感覺減退或消失。橈神經(jīng)麻痹伸腕、伸指及伸拇肌癱瘓（垂腕征）上肢主要神經(jīng)感覺分布區(qū)上肢主要神經(jīng)感覺分布區(qū)腓神經(jīng)麻痹足和足趾不能背屈、足下垂，步行時舉足高，足落地時足尖先著地，類似雞的步態(tài)，稱跨閾步態(tài)。感覺障礙：小腿外側(cè)和足背腓神經(jīng)麻痹足和足趾不能背屈、足下垂，步行時舉足高

9、，足落地時足不典型表現(xiàn)少數(shù)病人具有Charcot-Marie-Tooth表現(xiàn)；少數(shù)病人出現(xiàn)慢性多發(fā)性感覺神經(jīng)?。簧贁?shù)病人出現(xiàn)進(jìn)行性感覺運(yùn)動性單神經(jīng)病。不典型表現(xiàn)少數(shù)病人具有Charcot-Marie-Tooth電生理特點(diǎn)所有基因突變攜帶者，有癥狀或無癥狀者均出現(xiàn)彌漫性電生理異常：雙側(cè)正中神經(jīng)遠(yuǎn)端運(yùn)動潛伏期延長，伴雙側(cè)掌腕節(jié)段正中感覺神經(jīng)傳導(dǎo)速度減慢，以及至少有一條腓神經(jīng)的遠(yuǎn)端運(yùn)動潛伏期延長或運(yùn)動神經(jīng)傳導(dǎo)速度減慢；肘部尺神經(jīng)運(yùn)動神經(jīng)傳導(dǎo)速度減慢；下肢運(yùn)動神經(jīng)傳導(dǎo)速度中度減慢；感覺神經(jīng)動作電位降低，特別是上肢。電生理特點(diǎn)所有基因突變攜帶者，有癥狀或無癥狀者均出現(xiàn)彌漫性電Electrodiagnos

10、tic features of hereditary neuropathy with liability to pressure palsies NEUROLOGY 2000;54:4044 Nine HNPP subjects, 22 with CIDP and 49 with diabetic polyneuropathy. Of all the HNPP nerves studied, abnormally slow sensory nerve conduction velocity (SNCV) was found in 93%, prolonged distal motor late

11、ncies (DML) in 78%, slow motor nerve conduction velocity in 31%, and prolonged F-wave latencies in 90%. Mean SNCV for HNPP was 85.6% 10.6% of the lower limit of normal and significantly slower than for CIDP (114.3% 20.1%; p , 0.0001) or diabetes (108.1% 14.8%; p , 0.0001). Excluding the carpal tunne

12、l site from the analysis did not alter this observation: Mean DML were more prolonged in HNPP, even without median nerve data in the analysis (118.5% 31.0% of the upper limit of normal), than in CIDP (103.2% 31.6%; p , 0.05) or diabetes (86.3% 18.3%; p , 0.0001). Mean HNPP motor nerve conduction vel

13、ocity was within normal limits.Electrodiagnostic features of 病理學(xué)臘腸樣神經(jīng)病脫髓鞘和再生軸索變性病理學(xué)臘腸樣神經(jīng)病剝離單神經(jīng)纖維剝離單神經(jīng)纖維遺傳性壓力易感性遺傳性壓力易感性遺傳性壓力易感性臘腸樣神經(jīng)病HNPP：常見（50纖維），非常長（83m），直徑大（16 m ）；抗MAG神經(jīng)?。撼Ｒ姡?0纖維），長（46 m ），中等直徑（14 m ）；CIDP：偶爾（13纖維），長（56 m ），大直徑（19 m ）；CMT1A：偶爾（1030纖維），非常長（77 m ），中等直徑（14 m ）；CMT4B：非常常見（100纖維），長（4

14、4 m ），小直徑（11 m ）臘腸樣神經(jīng)病HNPP：常見（50纖維），非常長（83m）遺傳性壓力易感性遺傳性壓力易感性遺傳性壓力易感性遺傳性壓力易感性遺傳性壓力易感性遺傳性壓力易感性遺傳性壓力易感性遺傳性壓力易感性遺傳性壓力易感性遺傳性壓力易感性遺傳性壓力易感性遺傳性壓力易感性診斷標(biāo)準(zhǔn)European CMT consortium(Chairman: Professor C. Van Broeckhoven, Antwerpen, Belgium).1999.Neuromuscular Disorders 2000 (10) :206208. Guidelines for diagnosis

15、 of hereditary neuropathy with liability to pressure palsies.診斷標(biāo)準(zhǔn)European CMT consortium(ChDifferential DiagnosisPressure palsies are most commonly the result of environmentally acquired physical compression of peripheral nervesThe most common are the carpal tunnel syndrome with compression of the m

16、edian nerve at the wrist, peroneal pressure palsy with compression of the superficial peroneal nerve at the fibular head, and ulnar nerve compression at the elbow. those with diabetes mellitus, are at increased risk for compression neuropathiesthe CMT syndrome hereditary neuralgic amyotrophy, a distinct disorder that maps to 17q Differential DiagnosisPressure治療Risk factors for pressure palsies, and thus activities to avoid, include prolonged sitting with legs crossed, occupations requiring repetitive movements of