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Exp Neurobiol 2014; 23(3): 266-269
Published online September 30, 2014
© The Korean Society for Brain and Neural Sciences
Jung-Hwan Oh1, Han Sang Lee2, Dong Min Cha3 and Sa-Yoon Kang1*
1Department of Neurology, JeJu National University Hospital , JeJu 690-767, 2Department of Neurology, Seoul National University Hospital, Seoul 110-744, 3Department of Ophthalmology, JeJu National University Hospital, JeJu 690-767, Korea
Correspondence to: *To whom correspondence should be addressed.
TEL: 82-64-717-1620, FAX: 82-64-757-8276
Charcot-Marie-Tooth disease (CMT) 2A with optic atrophy is referred to as hereditary motor and sensory neuropathy type VI (HMSN VI) and is caused by mitofusin 2 gene (
Keywords: hereditary motor and sensory neuropathy, magnetic resonance imaging, mitofusin, mitochondria
Hereditary neuropathies are mainly divided into three subcategories: hereditary motor and sensory neuropathy (HMSN), hereditary sensory neuropathy (HSN), and hereditary motor neuropathy (HMN) , and these disorders are related with mutations in about 50 genes . Charcot-Marie-Tooth disease (CMT), also known as HMSN, is one of the most common inherited neuropathies, affecting approximately 1 in 2,500 people . Most forms of CMT are inherited in an autosomal dominant fashion. CMTs are traditionally divided into two types: demyelinating neuropathy or abnormal myelination, also called HMSN-I (CMT1), and axonal neuropathy, also called HMSN-II (CMT2) . Symptoms of CMT vary including peripheral neuropathy symptoms, optic nerve atrophy, spastic paraparesis, retinitis pigmentosa and others [1,2]. HMSN VI is an axonal CMT 2A with optic atrophy . HMSN VI is caused by mutations in mitofusin 2 (
A 47-year old woman visited our hospital with a chief complaint of visual impairment in both eyes. The patient had muscle weakness and atrophy in distal lower extremities from about 7 years old, and used a wheelchair due to a disability that makes ambulation impossible as symptoms deteriorated. Muscle weakness and atrophy in both hands developed from about 20 years old. Her symptoms gradually deteriorated and the affected area expanded to the entire upper extremities. Four months before her visit to our hospital, visual acuity in both eyes had gradually reduced. Recently, she had a difficulty in recognizing people's faces from a 5m distance, but had no color vision deficiency or ocular pain. She had normal cognitive function development and achieved outstanding academic grades. After finishing graduate school, she is currently working as a teacher.
Physical examination revealed that the patient had normal cognitive function, and her pupils were 3 mm/3 mm, symmetric and reactive to light. According to ophthalmologic examination, corrected visual acuity was 20/130 in the right eye and 20/200 in the left eye, and uncorrected visual acuity was 20/500 in the right eye and 20/1,000 in the left eye. Although the retina was normal in all eyes on slit lamp examination, bilateral optic disc pallor was detected on the temporal sides in fundus photogram (Fig. 1). Visual field constriction was not observed, but central scotoma in both eyes was found on Goldmann perimetry (Fig. 2). She had no motor disturbances in the extraocular and facial muscles. Dysarthria and dysphagia were not detected. Diffuse muscle weakness and atrophy were observed in both upper and lower extremities, and the symptoms were more severe in the distal extremities. The sensory function was normal, and tendon reflexes were absent in both upper and lower extremities. Babinski reflexes were negative.
There were no electric pontentials in sensory and motor nerve conduction studies and needle electromyographic examinations revealed giant motor unit action potentials and reduced interference patterns. Pattern reversal visual evoked potentials were significantly prolonged in both eyes. MRI scanning of the cerebral hemispheres, orbits and optic nerves was normal, but high signal intensities were found in bilateral middle cerebellar peduncles on diffusion-weighted and fluid attenuated inversion recovery (FLAIR) imaging (Fig. 3). Her routine blood laboratory studies were normal, and serum lactate level was also normal at 2.5 mmol/L. She is the eldest daughter of a son and five daughters. No family members had symptoms of neuromuscular disorders.
We analyzed exons 1~19 of
Nicholson et al.  first identified
Although MFN2 is ubiquitously expressed in the whole nervous system , it does not explain why involvement of the central nervous system is relatively rare compared to that of the peripheral nervous system in patients with