Biallelic variants in PLEKHG5 have been reported so far associated with different clinical phenotypes including Lower motor neuron disease (LMND) [also known as distal hereditary motor neuropathies (dHMN or HMN) or distal spinal muscular atrophy (DSMA4)] and intermediate Charcot-Marie-Tooth disease (CMT). We report four patients from two families presenting with intermediate CMT and atypical clinical and para-clinical findings. Patients presented with predominant distal weakness with none or mild sensory involvement and remain ambulant at last examination (22–36 years). Nerve conduction studies revealed, in all patients, intermediate motor nerve conduction velocities, reduced sensory amplitudes and multiple conduction blocks in upper limbs, outside of typical nerve compression sites. CK levels were strikingly elevated (1611–3867 U/L). CSF protein content was mildly elevated in two patients. Diffuse bilateral white matter lesions were detected in one patient. Genetic analysis revealed three novel frameshift variants c.1835_1860del and c.2308del (family 1) and c.104del (family 2). PLEKHG5-associated disease ranges from pure motor phenotypes with predominantly proximal involvement to intermediate CMT with predominant distal motor involvement and mild sensory symptoms. Leukoencephalopathy, elevated CK levels and the presence of conduction blocks associated with intermediate velocities in NCS are part of the phenotype and may arise suspicion of the disease, thus avoiding misdiagnosis and unnecessary therapeutics in these patients.

PLEKHG5 中的双等位基因变体迄今为止已报道与不同的临床表型相关，包括下运动神经元病 (LMND) [也称为远端遗传性运动神经病 (dHMN 或 HMN) 或远端脊髓性肌萎缩症 (DSMA4)] 和中间型夏科-玛丽-牙病 (CMT) ）。我们报告了来自两个家庭的四名患者，他们表现出中度 CMT 和非典型的临床和副临床发现。患者表现为主要的远端无力，没有或轻度感觉受累，并且在最后一次检查（22-36 岁）时仍能行走。神经传导研究显示，在所有患者中，在典型的神经压迫部位之外，上肢的运动神经传导速度为中等，感觉振幅降低和多处传导阻滞。CK 水平显着升高 (1611-3867 U/L)。两名患者的脑脊液蛋白含量轻度升高。在一名患者中检测到弥漫性双侧白质病变。遗传分析揭示了三个新的移码变体 c.1835_1860del 和 c.2308del（家族 1）和 c.104del（家族 2）。PLEKHG5相关疾病的范围从主要是近端受累的纯运动表型到主要是远端运动受累和轻微感觉症状的中间 CMT。白质脑病、CK 水平升高以及与 NCS 中速相关的传导阻滞的存在是表型的一部分，可能会引起对该疾病的怀疑，从而避免对这些患者的误诊和不必要的治疗。