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 . 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 . since the central nervous system has a large potential oxidative capacity due to the high level of oxygen consumption , involvement of the central nervous system is an unsurprising event in patients with cmt associated with mfn2 mutation . according to a recent study of chung et al .   which has a relatively large number of patients with mfn2 related cmt , cerebral involvements are detected in 38% ( 8 of 21 ) of all subjects , and most patients have white - matter lesions on brain mri scanning . the isolated involvement of bilateral middle cerebellar peduncles has been very rarely reported in patients with hmsn vi , therefore , we report this rare case with a brief review of literature . 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 . 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 5 m distance , but had no color vision deficiency or ocular pain . 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 . visual field constriction was not observed , but central scotoma in both eyes was found on goldmann perimetry ( fig . 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 . 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 . 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 . her routine blood laboratory studies were normal , and serum lactate level was also normal at 2.5 mmol / l . we analyzed exons 1~19 of mfn2 and their franks region by direct cycle sequencing , and identified heterozygous transversion of cytosine to thymine ( c.617c > t ) in the seventh coding exon , when compared with the reference sequences(nc_000001.10 , nm_014874.3 ) . mitochondrial dna mutations associated with leber 's hereditary optic atrophy ( 3460g > a , 11778g > a , 14484t > c and 4171c > a ) were not found . because the patient had not only peripheral neuropathy but also optic atrophy , she was diagnosed with hmsn vi caused by mfn2 mutation . nicholson et al .   first identified mfn2 mutations on chromosome 1p 36 in patients with hmsn vi , and mutations in mfn2 gene were also related with cmt2a and cmt5 . mfn2 is a mitochondrial outer membrane gtpase and is related with fusion and fission of mitochondria . opa1 ( optic atrophy 1 ) , located in the inner mitochondrial membrane , is associated with the most common type of pure autosomal dominant optic atrophy . since mfn2 and opa1 have complimentary functions of mitochondrial dynamics , mfn2 related cmt tends to involve the periventricular white matter rather than the cerebral cortex in the central nervous system . baloh et al . have asserted that the distal axons far from cell bodies of neurons are inclined to have an altered energy metabolism in the mfn2 mutant peripheral neurons , because the mitochondria supplement was insufficient in the region of the axons . interestingly , the patient had lesions only in the bilateral middle cerebellar peduncles on brain mri scanning . the middle cerebellar peduncles are paired structures that connect the cerebellum with axons of long motor and sensory neurons arising from the cerebral cortex through pontine nuclei . therefore , the lesions are likely to occur only in middle cerebellar peduncles because of insufficient mitochondrial trafficking compared to the cerebral white matter , which is composed of relatively shorter axons from cell bodies . moreover , bilateral middle cerebellar peduncles were altered , mostly due to the neurodegenerative disease . since mitochondrial dysfunction is a substantially significant cause for neurodegenerative diseases , mfn 2 related diseases such as hmsn vi seem to be profoundly associated with degeneration of the middle cerebellar peduncle . although a previous study reported the only case of involvement of the middle cerebellar peduncles in a patient with hmsn vi , brain mri images were not provided . in the case , mfn2 mutation site was c.1252c > t ( p.r418x ) , unlike the patient in our case . 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 mfn2 related cmt . the relationship between abnormal mitochondrial function caused by mfn2 mutation and involvement of the central nervous system still remains unclear . for this reason , additional studies are required and brain imaging techniques including mri will be beneficial in clarifying the pathogenic mechanism , in addition to providing diagnostic clues , in patients with hereditary motor and sensory neuropathy .
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 ( mfn2 ) mutation . in patients with 
 mfn2 related cmt , central nervous system is known to be also involved and cerebral white matter is mostly involved . 
 we report a patient confirmed as hmsn vi who had isolated bilateral middle cerebellar peduncular lesions in brain mri .