背景:Charcot-Marie-Tooth(CMT)是一组遗传性周围神经病变,其特征是广泛的基因型和表型变异性。发病通常在儿童时期,最常见的临床表现主要是远端肌无力,感觉减退,足畸形(pes腔)和无反射。从长远来看,并发症,如肌肉肌腱缩回,四肢畸形,可能会出现肌肉萎缩和疼痛。在CMT1,脱髓鞘和常染色体显性形式,CMT1G由PMP2髓磷脂蛋白中的突变决定。
结果:从索引案例开始,我们做了一个临床,电生理学,对所有家庭成员进行三代的神经放射学和遗传评估;我们在所有9名受影响的成员中确定了PMP2中的p.Ile50del。他们表现出典型的临床表型,儿童期发病的严重程度在几代人之间不同,在电生理检查中出现慢性脱髓鞘性感觉运动多发性神经病;进展缓慢至非常缓慢,并在下肢占优势。我们的研究报告了相对较大的患者样本,同一个家族的成员,用CMT1G通过PMP2,这是一种罕见的脱髓鞘CMT,强调CMT家族的遗传变异性,而不是脱髓鞘形式中重叠的临床表型。迄今为止,只有针对最严重并发症的支持和预防措施可用;因此,我们相信早期诊断(临床,电生理和遗传)允许获得专家随访和治疗,从而提高患者的生活质量。
BACKGROUND: Charcot-Marie-Tooth (CMT) is a group of inherited peripheral neuropathies characterized by wide genotypic and phenotypic variability. The onset is typically in childhood, and the most frequent clinical manifestations are predominantly distal muscle weakness, hypoesthesia, foot deformity (pes cavus) and areflexia. In the long term, complications such as muscle-tendon retractions, extremity deformities, muscle atrophy and pain may occur. Among CMT1,
demyelinating and autosomal dominant forms, CMT1G is determined by mutations in the PMP2 myelin protein.
RESULTS: Starting from the index
case, we performed a clinical, electrophysiological, neuroradiological and genetic evaluation of all family members for three generations; we identified p.Ile50del in PMP2 in all the nine affected members. They presented a typical clinical phenotype, with childhood-onset variable severity between generations and a chronic demyelinating sensory-motor polyneuropathy on the electrophysiologic examination; the progression was slow to very slow and predominant in the lower limbs. Our study
reports a relatively large sample of patients, members of the same family, with CMT1G by PMP2, which is a rare form of
demyelinating CMT, highlighting the genetic variability of the CMT family instead of the overlapping clinical phenotypes within
demyelinating forms. To date, only supportive and preventive measures for the most severe complications are available; therefore, we believe that early diagnosis (clinical, electrophysiological and genetic) allows access to specialist follow-up and therapies, thereby improving the quality of life of patients.