背景:早期生长反应2(EGR2)基因的突变会导致各种遗传性神经病,包括脱髓鞘Charcot-Marie-Tooth(CMT)疾病1D(CMT1D),先天性低髓鞘性神经病1型(CHN1),Déjerine-Sottas综合征(DSS),轴突CMT(CMT2)。
方法:在本研究中,我们确定了14例在2000~2022年间诊断出EGR2杂合突变的患者.
结果:平均年龄为44岁(15-70岁),10名患者为女性(71%),平均病程为28年(1-56)。9例(64%)发病年龄在15岁之前,35岁后有4例(28%),1例26岁患者无症状(7%).所有有症状的患者均有pes腔静脉和下肢远端无力(100%)。86%的病例观察到下肢远端感觉症状,手部萎缩71%,脊柱侧弯占21%。神经传导研究显示,在所有病例中(100%),主要是脱髓鞘性感觉运动神经病。5例患者在平均病程50年后需要步行辅助(47-56)(36%).3例患者被误诊为炎性神经病,并接受免疫抑制药物治疗多年,直到诊断得到纠正。两名患者出现了额外的神经系统疾病,包括Steinert肌强直性营养不良和脊髓小脑共济失调(14%)。发现8个EGR2基因突变,包括4个以前没有描述的。
结论:我们的发现表明EGR2基因相关的遗传性神经病是罕见的缓慢进行性脱髓鞘神经病,有2种主要临床表现,包括儿童期发病的变异体和可能模拟炎性神经病变的成人发病的变异体。我们的研究还扩展了EGR2基因突变的基因型谱。
Mutations in the Early-Growth Response 2 (EGR2) gene cause various hereditary neuropathies, including demyelinating Charcot-Marie-Tooth (CMT) disease type 1D (CMT1D), congenital hypomyelinating neuropathy type 1 (CHN1), Déjerine-Sottas syndrome (DSS), and axonal CMT (CMT2).
In this study, we identified 14 patients with heterozygous EGR2 mutations diagnosed between 2000 and 2022.
Mean age was 44 years (15-70), 10 patients were female (71%), and mean disease duration was 28 years (1-56). Disease onset was before age 15 years in nine cases (64%), after age 35 years in four cases (28%), and one patient aged 26 years was asymptomatic (7%). All symptomatic patients had pes cavus and distal lower limbs weakness (100%). Distal lower limbs sensory symptoms were observed in 86% of cases, hand atrophy in 71%, and scoliosis in 21%. Nerve conduction studies showed a predominantly demyelinating sensorimotor neuropathy in all cases (100%), and five patients needed walking assistance after a mean disease duration of 50 years (47-56) (36%). Three patients were misdiagnosed as inflammatory neuropathy and treated with immunosuppressive drugs for years before diagnosis was corrected. Two patients presented with an additional neurologic disorder, including Steinert\'s myotonic dystrophy and spinocerebellar ataxia (14%). Eight EGR2 gene mutations were found, including four previously undescribed.
Our findings demonstrate EGR2 gene-related hereditary neuropathies are rare and slowly progressive demyelinating neuropathies with two major clinical presentations, including a childhood-onset variant and an adult-onset variant which may mimic inflammatory neuropathy. Our study also expands the genotypic spectrum of EGR2 gene mutations.