Fusco Carlo, Spagnoli Carlotta, Salerno Grazia Gabriella, Pavlidis Elena, Frattini Daniele, Pisani Francesco, Bassi Maria Teresa
Department of Pediatrics, Child Neurology Unit, Santa Maria Nuova Hospital, IRCCS, viale Risorgimento 80, 42123 Reggio Emilia, Italy. Department of Pediatrics, Pediatric Neurophysiology Laboratory, Santa Maria Nuova Hospital, IRCCS, viale Risorgimento 80, 42123 Reggio Emilia, Italy..
Acta Biomed. 2019 Jan 24;90(1):104-107. doi: 10.23750/abm.v90i1.6951.
Childhood-onset peripheral neuropathies are often of genetic origin. Charcot-Marie-Tooth (CMT), is considered the commonest neuromuscular disorder. Due to its high clinical heterogeneity, especially in the pediatric age, the co-existence of central and peripheral symptoms and signs does not necessarily rule out a diagnosis of hereditary peripheral neuropathy.
We describe the clinical, neurophysiological and genetic findings in a teen-age patient evaluated for acquired toe-walking and progressive difficulties in walking since the age of 5. Genetic testing was carried out with a targeted NGS panel. Identified variants are analyzed using Variant Studio program (Illumina). Rare variants and variants considered as pathogenic were analyzed by Sanger direct sequencing.
The coexistence of peripheral and pyramidal signs in the lower limbs, the absence of a significant pre/perinatal history, the unremarkable brain and spine MRI, together with the presence of a sensory-motor polyneuropathy in all four limbs, prompted the execution of genetic investigations with an NGS panel covering hereditary spastic paraplegias, motor neuron disease and Charcot-Marie-Tooth. We identified a previously undescribed variant (c.1142G>T, p.Arg381Leu) in the EGR2 gene.
ERG2 gene has been described as a cause of various phenotypes, including a rare autosomal dominant form of CMT (CMT type 1D) representing approximately 1% of all CMT subgroups. We describe a novel pathogenic variant in EGR2 gene leading to the development of a complex association of peripheral and central neurological signs, underscoring the genetic and clinical heterogeneity of hereditary neuropathies of pediatric onset.
儿童期起病的周围神经病通常源于遗传。夏科-马里-图思病（CMT）被认为是最常见的神经肌肉疾病。由于其高度的临床异质性，尤其是在儿童期，中枢和周围症状及体征并存并不一定排除遗传性周围神经病的诊断。
我们描述了一名青少年患者的临床、神经生理学和遗传学检查结果，该患者自5岁起因后天性足尖行走和进行性行走困难接受评估。使用靶向二代测序（NGS） panel进行基因检测。使用Variant Studio程序（Illumina）分析鉴定出的变异。通过桑格直接测序分析罕见变异和被认为是致病性的变异。
下肢周围和锥体束征并存、无明显的产前/围产期病史、脑和脊柱MRI无异常，以及四肢均存在感觉运动性多发性神经病，促使我们使用涵盖遗传性痉挛性截瘫、运动神经元病和夏科-马里-图思病的NGS panel进行基因研究。我们在EGR2基因中鉴定出一个先前未描述的变异（c.1142G>T，p.Arg381Leu）。
ERG2基因已被描述为多种表型的病因，包括一种罕见的常染色体显性形式的CMT（CMT 1D型），约占所有CMT亚组的1%。我们描述了EGR2基因中的一种新型致病变异，该变异导致了周围和中枢神经系统体征的复杂关联，突显了儿童期起病的遗传性神经病的遗传和临床异质性。
