De Jonghe Peter, Jordanova Albena K
VIB Department of Molecular Genetics, University of Antwerp, Antwerpen, Belgium
NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.
Charcot-Marie-Tooth neuropathy type 2E/1F (CMT2E/1F) is characterized by a progressive peripheral motor and sensory neuropathy with variable clinical and electrophysiologic expression. Disease onset ranges from the first to the fifth decade of life; in some cases disease onset can be in infancy. Affected individuals have difficulty walking and running because of progressive distal weakness and wasting of the muscles of the lower limbs. Paresis in the distal part of the lower limbs varies from mild weakness to a complete paralysis of the distal muscle groups. Tendon reflexes are diminished or absent. Sensory signs are not prominent but are present in all affected individuals. , hammer toes, and claw hands are frequently observed. Ambulation is generally preserved.
DIAGNOSIS/TESTING: In most individuals, nerve conduction velocities (NCVs) are severely to moderately reduced and fall within the CMT1 range (i.e., <38 m/sec for the motor median nerve), although near-normal NCVs have been described. encoding the protein neurofilament light chain, is the only gene known to be associated with CMT2E/1F.
Affected individuals are often evaluated and managed by a multidisciplinary team that includes neurologists, physiatrists, orthopedic surgeons, and physical and occupational therapists. Treatment may include: special shoes with good ankle support, daily heel cord stretching exercises, ankle/foot orthoses, orthopedic surgery for severe deformity, and crutches or canes for stability. Exercise is encouraged. Pain is treated symptomatically. Daily heel cord stretching exercises to prevent Achilles' tendon shortening. Monitoring gait and condition of feet to determine need for bracing, special shoes, surgery. Obesity because it makes walking more difficult; drugs and medications (e.g., vincristine, isoniazid, taxol, cisplatin, nitrofurantoin) that are known to cause nerve damage.
CMT2E/1F is usually inherited in an autosomal dominant manner; on rare occasion it can be inherited in an autosomal recessive manner. Most individuals with autosomal dominant CMT2E/1F have an affected parent. pathogenic variants are more typical for individuals with a severe phenotype. The risk to sibs depends on the genetic status of the proband's parents. Each child of an individual with autosomal dominant CMT2E/1F has a 50% chance of inheriting the pathogenic variant. The risk to each sib of an affected individual at conception is 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Prenatal testing for pregnancies at increased risk for both autosomal dominant and autosomal recessive CMT2E/1F is possible if the pathogenic variant(s) in the family are known.
注意：本出版物已停用。此存档版本仅用于历史参考，信息可能过时。
2E/1F型夏科-马里-图斯神经病变（CMT2E/1F）的特征是进行性周围运动和感觉神经病变，临床和电生理表现各异。发病年龄范围从生命的第一个十年到第五个十年；在某些情况下，发病可在婴儿期。由于下肢肌肉进行性远端无力和萎缩，受影响个体行走和跑步困难。下肢远端轻瘫程度从轻度无力到远端肌群完全麻痹不等。腱反射减弱或消失。感觉体征不突出，但所有受影响个体均有。常观察到锤状趾和爪形手。一般可保持行走能力。
诊断/检测：在大多数个体中，神经传导速度（NCV）严重至中度降低，落在CMT1范围内（即运动正中神经<38米/秒），尽管也有描述NCV接近正常的情况。编码神经丝轻链蛋白的基因是已知与CMT2E/1F相关的唯一基因。
受影响个体通常由包括神经科医生、物理医学与康复医生、骨科医生以及物理治疗师和职业治疗师在内的多学科团队进行评估和管理。治疗可能包括：具有良好脚踝支撑的特制鞋子、每日跟腱拉伸运动、踝/足矫形器、针对严重畸形的矫形手术，以及用于稳定的拐杖或手杖。鼓励进行锻炼。对疼痛进行对症治疗。每日进行跟腱拉伸运动以防止跟腱缩短。监测步态和足部状况以确定是否需要支具、特制鞋子或手术。肥胖会使行走更加困难；已知会导致神经损伤的药物（如长春新碱、异烟肼、紫杉醇、顺铂、呋喃妥因）。
CMT2E/1F通常以常染色体显性方式遗传；极少数情况下可呈常染色体隐性遗传。大多数常染色体显性CMT2E/1F个体有患病的父母。致病变异在具有严重表型的个体中更为典型。同胞的患病风险取决于先证者父母的基因状况。常染色体显性CMT2E/1F个体的每个孩子有50%的机会继承致病变异。受影响个体的每个同胞在受孕时受影响的几率为25%，无症状携带者的几率为50%，未受影响且非携带者的几率为25%。如果家族中的致病变异已知，对于常染色体显性和常染色体隐性CMT2E/1F患病风险增加的妊娠可进行产前检测。
