| Background:FSHD is characterized by onset of weakness in an initially restricted andcharacteristic distribution,starting with facial weakness,and followed sequentially byscapular fixator,humeral weakness,and the clinical syndrome of FSHD was first described byLouis landouzy and Dejerine in1884.It is a dominantly inherited neuromuscular disorderand is the third most common dystrophy after the dystrophinopathies and myotonic musculardystrophy.The best estimate of prevalence is1:20000,with greater than95%of affectedindividuals showing signs by age20,the rate of progression is generally slow and steady.TheFSHD locus was mapped to the subtelomeric portion of chromosome4(4q35)in1990.Clinical diagnosis of FSHD can be made with the manifestations，pathophysiology andthe number of a repetitive element(3.3kb/KpnI) in the4q subtelomeric region.Objectives:To analyze the most common symptoms and clinical manifestations offacioscapulohumeral muscular dystrophy. Analyze serum myocardial enzymes changes andpathological features, evaluate the clinical severity of facioscapulohumeral musculardystrophy, and analyze the relationship between all the factors(age of onset、course ofdisease、initial symptoms) and the clinical severity.FSHD can mimic acquired polymyositis(PM) in particular when inflammatory infiltrates are present on muscle biopsy. For bettercharacterization of inflammatory response in FSHD, we performed histochemicalmorphological analysis for three groups of muscles; FSHD, PM and control musclebiopsies.In order to provide a reference for clinical diagnosis and guide targeted therapeuticinterventions.Materials and Methods:According to the diagnostic criteria,choose the out-patientand in-patient cases who were diagnosed as facioscapulohumeral muscular dystrophy indepartments of Neurology in the first hospital of jilin university.Collection the clinical datasof24cases from Sep.2006to Oct.2011period. The clinical datas include: gender, age,history, symptoms, signs, serum myocardial enzymes level, electrophysiological study,muscle pathology histochemistry dyeing and immunohistochemical staining, and thencompared, analyzed and summarized the results. the general index of all patients. For bettercharacterization of inflammatory response in FSHD, we performed histochemicalmorphological analysis for three groups of muscles：FSHD, PM and control muscle biopsies. Each parameter of myopathy was evaluated in five or ten randomly, selected fields, usingImage-Pro plus bioanalytical software. Comparison between groups was tested by twosample t-test analysis.Results:1.There is no significant gender differences in FSHD. Mean age of onset is20.33±7.36岁.Progression is descending,there is wide variability in disease severity.Theclinical presentation is characterized by an initially restricted distribution of weaknessfollowed sequentially by scapular fixator,humeral,truncal,and lower extremity weakness. Inour group,33.3%noticed facial muscle weakness as the first symptom,25%of patientsnoticed shoulder girdle weakness.The most commonly affected facial muscles are theorbicularis oculi(83.3%) and the orbicularis oris(83.3%). Extraocular and bulbar muscles aretypically spared in FSHD. The most commonly affected shoulder girdle muscles aresupraspinatus muscle(91.7%)，infraspinatus muscle(91.7%)，serratus anterior muscle(91.7%)，major pectoral muscle(50%)，biceps brachii(79.2%)and triceps brachii(66.7%).The weakness often is asymmetric，and this feature distinguishes FSHD from limbgirdle dystrophy.2.The most common feature is winged scapula(marked winging of thescapula on active shoulder flexion or abduction).Other signs includes:Gower sign, waddlinggait,positive Beevor’s sign (a physical finding fairly specific for FSHD)，scoliosis andpseudo muscular hypertrophy.3.An extreme variation in onset， clinical features andseverity is showed even within a family with all affected members carrying the same geneticlesion, and there is a heredity anticipation phenomenon (an earlier onset and more severephenotype in subsequent generations)in family members.4.The age of onset haverelationship with the clinical severity of the disease, the earlier the onset is, the severer thephenotype is.5. Serum myocardial enzymes was normal or lightly high, the lever of which islower than five as normal. Electrophysiological study shows myopathic defect.6.Routinehistochemical studies show typical dystrophic features, including various degrees ofmuscle-fiber degeneration and regeneration, variation in fiber size with small round fibers,muscle fiber atrophy, hypertrophy, internal nuclei, increased membranous nuclei, fewershows nuclei aggregation.The diameter of atrophied muscle fiber range from10μm to70μmsizes, round in shape in cross section, there are opaque fibers and Whirlpool fibers.AbnormalNADH-TR stained fibers include: moth-eaten; lobulated and intermyofibrillar networkdisorder. Connective tissue showed considerable proliferation in some patients and mayshows perimysial and perivascular T-cell infiltrates.Immunohistochemical staining with dystrophin-N,-C,-R，dysferlin，sarcoglycan and laminA/C monoclonal antibody normallyexpressed,3cases MHC-I up-regulated.7. There was larger mean surface area and longermean diameter of muscle fibers in the muscle of FSHD patients than in PM. However, thedifferences were irrelevant (p>0.05).We also measured muscle fibers’ mean density usingCOX stain to test whether dystrophic process causes change in mitochondrial enzymeactivity. Despite that, there was no large difference. In terms of cellular infiltrates, moreinflammatory cells per muscle fiber were observed in FSHD patients. Yet no statisticalimportance was reported (p>0.05).The regenerating and necrotic fibers showed nosignificant difference in FSHD and PM patients.Connective tissue showed considerableproliferation in FSHD with p value of0.02and <0.01from PM and CN patients respectively.Conclusion:1. The clinical spectrum of FSHD is wide ranging,age of onset is variable,with mostpatients becoming symptomatic in the second decade. Facial muscle weakness and shouldergirdle weakness is the most common first symptom. Serum myocardial enzymes was normalor lightly high, the lever of which is lower than five as normal. Electrophysiological studyshows myopathic defect.2.Routine histochemical studies show typical dystrophic features.Immunohistochemicalstaining with dystrophin-N,-C,-R，dysferlin，sarcoglycan and laminA/C monoclonalantibody normally expressed,3cases MHC-I up-regulated.3..Connective tissue showed considerable proliferation in FSHD with p value of0.02and <0.01from PM and CN patients respectively.4. In our group Family history of FSHD patients accounted for25%.An extremevariation in onset，clinical features and severity is showed even within a family with allaffected members carrying the same genetic lesion, and there is a heredity anticipationphenomenon in family members.5.The rank of FSHD’s clinical severity concentrated on2-7,the age of onset haverelationship with the clinical severity of the disease, the earlier the onset is, the severer thephenotype is. |
PDF Full Text Request