Zhuoting Liu1, Xia Guo1,2, Haokun Guo1, Jing Luo3, Fei Xiao4. 1. Department of Neurology, Chongqing Key Laboratory of Neurology, the First Affiliated Hospital of Chongqing Medical University, 1st Youyi Road, Yuzhong District, Chongqing, 400016, China. 2. Department of Neurology, The Second Affiliated Hospital of Zunyi Medical University, Intersection of Xinlong Avenue and Xinpu Avenue, Honghuagang District, Zunyi, Guizhou, China. 3. Department of Neurology, Chongqing Key Laboratory of Neurology, the First Affiliated Hospital of Chongqing Medical University, 1st Youyi Road, Yuzhong District, Chongqing, 400016, China. jgire@163.com. 4. Department of Neurology, Chongqing Key Laboratory of Neurology, the First Affiliated Hospital of Chongqing Medical University, 1st Youyi Road, Yuzhong District, Chongqing, 400016, China. feixiao81@126.com.
Abstract
BACKGROUND: Facial-onset sensory and motor neuronopathy (FOSMN) syndrome is a rare clinical syndrome in which the etiopathogenesis and disease-causing genes remain unknown. In addition, clinical and molecular pathological studies have rarely been evaluated in a large case series. METHODS: In this study, we present the clinical features and electrodiagnostic findings of the largest cohort of six patients with FOSMN in East Asia to date. Immunofluorescence assessment of TAR DNA-binding protein (TDP)-43 in muscle and skin fibroblasts, detection of GGC trinucleotide repeat expansions in NOTCH2NLC gene, and GGGGCC hexanucleotide repeat expansions in the C9orf72 gene were also performed. RESULTS: All patients exhibited typical symptoms and signs of FOSMN syndrome. Almost all patients showed a delayed or absent blink reflex. Neurogenic damage was found in five patients by electromyography. Two of the five patients with muscle and skin biopsies showed TDP-43-positive inclusions in both the nucleus and cytoplasm of muscular tissue and skin fibroblasts. There were no repeat expansions in the C9orf72 or NOTCH2NLC genes in any of the six patients. CONCLUSIONS: To date, this is the largest FOSMN cohort in East Asia. TDP-43-positive cytoplasmic inclusions in muscle and skin fibroblasts may be a pathologic feature of the disease. The patient's dynamic mutation test showed no GGC trinucleotide repeat expansions in the NOTCH2NLC and GGGGCC hexanucleotide repeat expansions in the C9orf72 gene. Further studies are needed with more patients.
BACKGROUND: Facial-onset sensory and motor neuronopathy (FOSMN) syndrome is a rare clinical syndrome in which the etiopathogenesis and disease-causing genes remain unknown. In addition, clinical and molecular pathological studies have rarely been evaluated in a large case series. METHODS: In this study, we present the clinical features and electrodiagnostic findings of the largest cohort of six patients with FOSMN in East Asia to date. Immunofluorescence assessment of TAR DNA-binding protein (TDP)-43 in muscle and skin fibroblasts, detection of GGC trinucleotide repeat expansions in NOTCH2NLC gene, and GGGGCC hexanucleotide repeat expansions in the C9orf72 gene were also performed. RESULTS: All patients exhibited typical symptoms and signs of FOSMN syndrome. Almost all patients showed a delayed or absent blink reflex. Neurogenic damage was found in five patients by electromyography. Two of the five patients with muscle and skin biopsies showed TDP-43-positive inclusions in both the nucleus and cytoplasm of muscular tissue and skin fibroblasts. There were no repeat expansions in the C9orf72 or NOTCH2NLC genes in any of the six patients. CONCLUSIONS: To date, this is the largest FOSMN cohort in East Asia. TDP-43-positive cytoplasmic inclusions in muscle and skin fibroblasts may be a pathologic feature of the disease. The patient's dynamic mutation test showed no GGC trinucleotide repeat expansions in the NOTCH2NLC and GGGGCC hexanucleotide repeat expansions in the C9orf72 gene. Further studies are needed with more patients.