Heterozygous D90A-SOD1 mutation in a patient with facial onset sensory motor neuronopathy (FOSMN) syndrome: a bridge to amyotrophic lateral sclerosis
Heterozygous D90A-SOD1 mutation in a patient with facial onset sensory motor neuronopathy (FOSMN) syndrome: a bridge to amyotrophic lateral sclerosis
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DOI：
10.1136/jnnp-2013-307416
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发表时间：
2014-09-01
影响因子：
11
通讯作者：
Lauria, Giuseppe
中科院分区：
文献类型：
--
作者：
Dalla Bella, Eleonora;Rigamonti, Andrea;Lauria, Giuseppe
目的描述1例与超氧化物歧化酶（SOD 1）基因D90A杂合突变相关的面源性感觉运动神经元病（FOSMN）综合征。方法对该患者进行神经系统和神经生理学检查，包括瞬目反射、颌反射、腓肠神经和皮肤活检，并进行TARDBP、FUS和C9ORF72基因分析。结果神经系统检查显示弥漫性肌束震颤、延髓征、面、颈、肩带及第一骨间肌萎缩无力，角膜反射消失。神经生理学研究显示异常眨眼和颌反射和上肢感觉神经动作电位降低。腓肠神经和皮肤活检显示大小神经纤维轻度丢失。结论FOSMN综合征最近被描述在缓慢进行性延髓和上肢肌萎缩的患者中。感觉症状，主要涉及三叉神经领域，通常先于运动无力发作数月或数年。FOSMN综合征的发病机制尚不清楚，可能的免疫介导机制已被提出。我们的研究结果支持这一假设，即FOSMN综合征是一种原发性退行性疾病，扩大了运动神经元疾病的范围。
Objective To describe a patient with facial onset sensory motor neuronopathy (FOSMN) syndrome associated with a heterozygous D90A mutation in superoxide dismutase (SOD1) gene.Methods The patient underwent neurological and neurophysiologic examinations, including blink and jaw reflexes, sural nerve and skin biopsies, and analysis of TARDBP, FUS and C9ORF72 genes.Results Neurological examination showed diffuse fasciculations, bulbar signs, hypotrophy and weakness of facial, neck, shoulder girdle and first interosseus muscles, and absent corneal reflex. Neurophysiologic studies demonstrated abnormal blink and jaw reflexes and reduced sensory nerve action potentials at upper limbs. Sural nerve and skin biopsies revealed mild loss of large and small nerve fibres. Genetic analysis demonstrated a heterozygous D90A-SOD1 mutation.Conclusions FOSMN syndrome has been recently described in patients with slowly progressive bulbar and upper limb amyotrophy. Sensory symptoms, mainly involving the trigeminal territory, typically precede the onset of motor weakness by months or years. The pathogenesis of FOSMN syndrome is unknown and possible immune-mediated mechanisms have been claimed. Our findings support the hypothesis that FOSMN syndrome is a primary degenerative disorder that widens the spectrum of motor neuron diseases.