The Clinical?Radiology?Myopathological Features And Genetic Analysis Of A Group Of Patients With Distal Myopathy

Background and Objectives:Distal myopathy is a rare and sporadic,autosomal dominant or recessive hereditary myopathy which is characterized as muscular weakness in the distal extremities,especially in lower extremities.In the past,the classification of distal myopathy are often depend on the clinical feature and muscle pathology.With the improvement of molecular biology and genetic diagnosis technology,more and more distal myopathy are classified by the changes of gene or protein.There are more than25 gene mutations related to distal myopathy so far,but many genes related to distal myopathy are not clear.The purpose of this study is to summarize the clinical characteristics,muscle pathology,and genetic analysis of patients with distal myopathy and provide a reference for the diagnosis of distal myopathy.Materials and methods:AII the 14 cases with distal myopathy were clinically diagnosed in the Department of Neurology,the First Affiliated Hospital of Nanchang University from January 2011 to March 2019.We summarized the clinical manifestations,serum creatine kinase,muscle magnetic resonance Imaging,muscle biopsy,and genetic analysis.Result:1.Clinical features:All of the 14 patients,9 were males and 5 were females,4 had similar family histories,3 were autosomal dominant inheritance.The onset age of patients were ranged from 4 to 57 years old,and the average onset age was 37.8 years old.The course of disease ranges from 2 years to 34 years.The initial symptom of the patient were as follows: 5 cases of fatigue of the lower limbs,3 cases of arms and legs weakness,3 cases of lower limbs weakness,1 case of dysphagia,1 case of right upper limb weakness,1 case of upper limbs weakness accompanied with eyelid ptosis.In the 14 patients,12 patients showed distal muscle strength less than proximal muscle strength,2 patients proximal muscle strength were equal to distal muscle strength.There were 7 cases of lower limbs atrophy,4 cases of upper and lower limbs atrophy,1 case of upper limb and 2 cases of no obvious atrophy in the limbs.2.Laboratory examinations:Serum creatine kinase was higher slightly in 5 patients and normal in 9 patients.13 patients had finished electromyography,4 patients' nerve conduction velocity and amplitude were reduced,2 patients' sensory nerve conduction velocity was not elicited.6 patients' action potential amplitude and time were narrowed,4 patients' action potential amplitude and time were increased.8 patients showed myogenic damage and 4 patients showed myogenic and neurogenic damage.The magnetic resonance imaging of the lower extremity muscles revealed muscle atrophy and steatosis were selective in both lower extremities ranging over the gastrocnemius,soleus muscle,tibialis anterior muscle,quadriceps muscle and son on.The involved muscles were more affected in the calf muscles than the leg muscles,the hip muscles were generally not implicated.3.Muscle pathological features:Muscle biopsy revealed 8 cases of muscle fiber atrophy accompanied with muscle fiber hypertrophy,5 cases of small horny or small round atrophic muscle fibers,6 cases of muscle fibers with rimmed vacuoles,1 case of typical spiral muscle fibers,and 1 case of eosinophilic cytoplasm in the muscle fibers.Immunohisto-chemical staining showed amorphous substance deposition in 2 patients,which were strongly positive for desmin,and one of them was moderately positive for ZASP.4.Gene mutation characteristics:Seven gene mutation sites were detected in the gene detection,BICD2 c.361C>G was detected in No.2 patient and her younger brother,TTNc.23332A>G was detected in No.5 patient,DESc.1256C>A was detected in No.7 patient,GNE2 c.527A>T was detected in No.11 patient,DMDc.10783C>A and POLG2 c.1400A>T were detected in No.13 patient,LDB3 c.463A> C was detected in No.14 and his relatives.GNE2 exon c.527A>T is a common hot spot mutation in Chinese and Japanese.Conclusions:1.The clinical manifestations of patients with distal myopathy was complex and diverse.The patients could get sick at any age.The main clinical characteristicsof distal myopathy were muscle weakness in the lower extremities.Some patients' eyelid muscles and throat muscle were involvement.Their CK was normal or mildly elevated.The EMG was characterized by myogenic damage in most patients,and a few patients had neurogenic damage.2.Muscle MRI suggested selective atrophy and steatosis in the lower extremities,calf muscles were more affected than thigh muscles.3.The muscle pathology of patients with distal myopathy was characterized by myopathy or muscular dystrophy changes and rimmed vacuole.A few patientes with distal myopathy showed neurogenic muscle damage.Protein deposition in muscle fibers is an important pathological feature of myofibrillar myopathy,which was contribute to clinical diagnosis.4.Distal myopathy were almost related to gene mutation,the targeting gene panel could improve clinical diagnosis and distinguish distal myopathy types.