Relationship Between Coronavirus Disease 2019 Vaccination Rates and Rare But Potentially Fatal Adverse Events: A Regression Discontinuity Analysis of Western Countries

Background@#Owing to limited experience with the new vaccine platforms, discussion of vaccine safety is inevitable. However, media coverage of adverse events of special interest could influence the vaccination rate; thus, evaluating the outcomes of adverse events of special interest influencing vaccine administration is crucial. @*Methods@#We conducted regression discontinuity in time analysis to calculate the local average treatment effect (LATE) using datasets from Our World in Data and Johns Hopkins University Center for Systems Science and Engineering. For the United States, the United Kingdom, and Europe, the cutoff points were April 23rd and June 23rd, April 7th, and the 14th week of 2021, respectively. @*Results@#The LATE of the Advisory Committee on Immunization Practices (ACIP) meeting held on April 23rd was −0.249 for all vaccines, −0.133 (−0.189 to −0.076) for Pfizer, −0.064 (−0.115 to −0.012) for Moderna, and −0.038 (−0.047 to −0.030) for Johnson & Johnson. Discontinuities were observed for all three types of vaccines in the United States. The June 23rd meeting of the ACIP (mRNA vaccines and myocarditis) did not convene any discontinuities. Furthermore, there was no significant drop in the weekly average vaccination rates in Europe following the European Medicines Agency (EMA) statement on April 7th. Conversely, there was a significant drop in the first-dose vaccination rates in the United Kingdom related to the EMA report. The first-dose vaccination rate for all vaccines changed by −0.104 (−0.176 to −0.032). @*Conclusion@#Although monitoring and reporting of adverse events of special interest are important, a careful approach towards public announcements is warranted.

Differences in Resumption of Orthopedic Surgery According to Characteristics of Surgery during COVID-19 Pandemic: National Registry Data

Background@#Healthcare services have been restricted after the coronavirus disease 2019 (COVID-19) outbreak. With the pandemic still ongoing, the patterns of orthopedic surgery might have changed. The purpose of this study was to determine whether the reduced volumes of orthopedic surgery were recovered over time. Among the trauma and elective surgery, which accounted for most orthopedic surgical procedures, we also sought to elucidate whether the changes in the volumes of orthopedic surgery differed according to the type of surgery. @*Methods@#The volumes of orthopedic surgery were analyzed using the Health Insurance Review and Assessment Service of Korea databases. The surgical procedure codes were categorized depending on the characteristics of the procedures. The actual volumes of surgery were compared with the expected volumes to elucidate the effect of COVID-19 on surgical volumes. The expected volumes of surgery were estimated using Poisson regression models. @*Results@#The reducing effect of COVID-19 on the volumes of orthopedic surgery weakened as COVID-19 continued. Although the total volumes of orthopedic surgery decreased by 8.5%–10.1% in the first wave, those recovered to a 2.2%–2.8% decrease from the expected volumes during the second and third waves. Among the trauma and elective surgery, open reduction and internal fixation and cruciate ligament reconstruction decreased as COVID-19 continued, while total knee arthroplasty recovered. However, the volumes of hemiarthroplasty of the hip did not decrease through the year. @*Conclusions@#The number of orthopedic surgeries, which had decreased due to COVID-19, tended to recover over time, although the pandemic was still ongoing. However, the degree of resumption differed according to the characteristics of surgery. The findings of our study will be helpful to estimate the burden of orthopedic surgery in the era of persistent COVID-19.

Clinical and Radiological Features of Korean Patients With Anti-HMGCR Myopathy

Background@#and Purpose To understand the characteristics of Korean patients with anti-3-hydroxy-3-methylglutaryl-coenxyme A reductase (HMGCR) myopathy, we measured antiHMGCR antibodies and analyzed the clinical, radiological, and pathological features of patients with anti-HMGCR myopathy. @*Methods@#We measured titers of anti-HMGCR antibodies in the sera of 99 patients with inflammatory myopathy, 36 patients with genetic myopathy, and 63 healthy subjects using an enzyme-linked immunosorbent assay. We tested 16 myositis-specific autoantibodies (MSAs) in all patients with anti-HMGCR myopathy. @*Results@#Positivity for the anti-HMGCR antibody was observed in 17 (4 males and 13 females) of 99 patients with inflammatory myopathy. The median age at symptom onset was 60 years.Ten (59%) of the patients with anti-HMGCR positivity had taken statins. The titer of antiHMGCR antibodies was significantly higher in the statin-naïve group (median=230 U/mL, interquartile range=170–443 U/mL) than in the statin-exposed group (median=178 U/mL, interquartile range=105–210 U/mL, p=0.045). The most common symptom was proximal muscle weakness in 15 patients (88%), followed by myalgia in 9 (53%), neck weakness in 4 (24%), dysphagia in 3 (18%), and skin lesions in 2 (12%). The median titer of anti-HMGCR antibody was 202 U/mL. We found eight different MSAs in nine (53%) patients. The median disease duration from symptom onset to diagnosis was significantly shorter in the MSA-positive group than in the MSA-negative group (p=0.027). @*Conclusions@#Our study was the first to measure anti-HMGCR antibodies in inflammatory myopathy. It has provided new findings, including the suggestion of the coexistence of other MSAs in Korean patients.

Incidence, Disability, and Mortality in Patients With Guillain-Barré Syndrome in Korea:A Nationwide Population-Based Study

Background@#and Purpose This study aimed to identify the epidemiological features of Guillain-Barré syndrome (GBS) in the Korean population. @*Methods@#Patients with GBS were defined as those who were hospitalized with a primary diagnostic code of G61.0 on the Korean Classification of Disease in a department of neurology, rehabilitation medicine, or pediatrics. We evaluated the incidence and prevalence of GBS as well as physical disability, mortality, and cause of death in patients with GBS from 2002 to 2018 in the Korean population using the Korean National Health Insurance Service database. @*Results@#We identified 11,146 patients with GBS. The ratio of males to females was 1.48. The age-adjusted incidence rate per 100,000 persons increased steadily from 0.84 in 2002 to 1.68 in 2018, as did the age-adjusted prevalence rate per 100,000 persons, from 0.77 to 15.62. The incidence and prevalence of GBS increased with age, peaking at 70–79 years. Among 10,114 patients without physical disability at the time of GBS being diagnosed, 502 (5.0%) patients had moderate disability and 526 (5.2%) had severe disability by the end of the study period.A total of 1,221 (11.0%) patients with GBS died during the mean follow-up period of 17 years (2002–2019). There were 144 (1.3%) in-hospital deaths. @*Conclusions@#This was the first nationwide epidemiological study of patients with GBS covering the entire population including patients of all ages in the Republic of Korea. We have revealed the seasonality of admissions, disability, and long-term mortality rates in patients with GBS.

A Familial Case with Phenotypic Differences in a CAV3 Pathogenic Variant / 대한신경근육질환학회지

We reported an age 32 male with progressive proximal muscle weakness. The serum creatine kinase was 1,908 IU/L. The muscle biopsy from biceps brachii muscle showed nonspecific myopathic changes. The whole exome sequencing identified a heterozygous variant (c.296A>C) in CAV3. It was previously reported as a likely pathogenic variant. It was also detected in the male’s mother and brother. However, his mother and brother had only hyperCKemia without muscle weakness. Our case showed phenotypic heterogeneity in a family, with the same variant in CAV3.

Validation of the Individualized Neuromuscular Quality of Life Questionnaire in Korean Patients With Genetic Neuromuscular Diseases

Background@#and Purpose The Individualized Neuromuscular Quality of Life questionnaire (INQoL) is a widely used measure of the quality of life in patients with neuromuscular diseases. The purpose of this study was to translate and validate the Korean version of INQoL in Korean patients with neuromuscular diseases. @*Methods@#We translated the original INQoL version into Korean while applying appropriate language adaptations. The internal consistency, known-group validity, and test-retest reliability were also assessed. Construct validity was measured using the modified Rankin Scale (mRS) score and the manual muscle testing (MMT)-sum score based on the Medical Research Council scale, and concurrent validity was measured using the 36-item Short Form Survey (SF-36) questionnaire. @*Results@#This study enrolled 193 patients. The coefficients for internal consistency (Cronbach’s α=0.805 to 0.987) and test-retest reliability (Spearman’s ρ=0.453 to 0.886) were adequately high for all subscales except in the ‘treatment effects’ dimension. INQoL subscales other than those for locking, droopy eyelids, double vision, and swallowing difficulties were significantly associated with their relevant SF-36 domains (Spearman’s ρ=-0.274 to -0.833). Functional status and muscle strength were most strongly associated with independence (Spearman’s ρ=0.753 and p<0.001 for mRS score, Spearman’s ρ=-0.741 and p<0.001 for MMT-sum score). @*Conclusions@#The Korean INQoL is a reliable and validated measurement tool for Korean patients with neuromuscular diseases.

Statin-Induced Immune-Mediated Necrotizing Myopathy with Anti-HMGCR Antibody / 대한신경근육질환학회지

Anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (anti-HMGCR) antibody related immune-mediated necrotizing myopathy (IMNM) are usually associated with statin use. The disease has features of persistent muscle weakness and creatine kinase (CK) elevation after statin discontinuation. This report describes a 65-year-old female taking atorvastatin, presenting with both proximal lower extremity weakness. IMNM feature were detected on muscle biopsy and high anti-HMGCR autoantibody titer on enzyme-linked immunosorbent assay (ELISA). This patient was treated with corticosteroid. Muscle weakness and CK are improved after immunosuppressive therapy.

Clinical Features and Brain MRI Findings in Korean Patients with AGel Amyloidosis

Purpose@#AGel amyloidosis is systemic amyloidosis caused by pathogenic variants in the GSN gene. In this study, we sought to characterize the clinical and brain magnetic resonance image (MRI) features of Korean patients with AGel amyloidosis. @*Materials and Methods@#We examined 13 patients with AGel amyloidosis from three unrelated families. Brain MRIs were performed in eight patients and eight age- and sex-matched healthy controls. Therein, we analyzed gray and white matter content using voxel-based morphometry (VBM), tract-based spatial statistics (TBSS), and FreeSurfer. @*Results@#The median age at examination was 73 (interquartile range: 64–76) years. The median age at onset of cutis laxa was 20 (interquartile range: 15–30) years. All patients over that age of 60 years had dysarthria, cutis laxa, dysphagia, and facial palsy. Two patients in their 30s had only mild cutis laxa. The median age at dysarthria onset was 66 (interquartile range: 63.5–70) years. Ophthalmoparesis was observed in three patients. No patient presented with muscle weakness of the limbs. Axial fluid-attenuated inversion recovery images of the brain showed no significant differences between the patient and control groups. Also, analysis of VBM, TBSS, and FreeSurfer revealed no significant differences in cortical thickness between patients and healthy controls at the corrected significance level. @*Conclusion@#Our study outlines the clinical manifestations of prominent bulbar palsy and early-onset cutis laxa in 13 Korean patients with AGel amyloidosis and confirms that AGel amyloidosis mainly affects the peripheral nervous system rather than the central nervous system.

Rhino-orbito-cerebral Actinomycosis Infection

Purpose@#To report a case of actinomycosis infection originating in the orbitonasal cavity that quickly invaded the cerebrum.Case summary: A-57-year-old male with a history of right tooth extraction 7 days before the first visit presented with right eyelid swelling and pain that had developed 4 days prior to the visit and had become increasingly worse. The best-corrected visual acuity was light perception. The intraocular pressure of the patient was 37 mmHg in the right eye. Eyelid abscess, subconjunctival hemorrhage, and severe chemosis was observed. Orbital computed tomography showed multiple air pockets and enhancing soft tissue along the periorbital, maxillary, and ethmoid sinus. Emergent endoscopic sinus surgery, lateral canthotomy, and intravenous antifungal treatment were performed due to suspicion of mucormycosis infection. Two days after treatment, exenteration combined with otolaryngology and neurosurgery were performed, as brain magnetic resonance imaging scans indicated that intraorbital lesions had invaded the dura and frontal sinus. On Day 8 of treatment, Actinomyces odontolyticus was identified and intravenous Ampicillin was administered. Despite systemic antibiotic treatment, the infection could not be controlled. The patient died 28 days after treatment due to persistent intracranial hemorrhage and brain edema. @*Conclusions@#For patients with severe eyelid swelling with a history of tooth extraction, actinomycosis infection should be considered. Delays in diagnosis and treatment of this infection could lead to serious consequences.

Clinical Scales for the Evaluation of Myopathy Patients

With the rapid increase in the number of clinical trials in myopathy over the past decade, there is an increasing need for clinical scales to reflect patient’s clinical status. This article outlines the process of identifying possible measures. Detailed consideration has been given to key measures of muscle strength, function, and disability. As well as the usual assessment of the validity and reliability of the measures, three key characteristics were identified as necessary to the assessment of clinical scales used in health care: 1) the type of scale; 2) the clinical significance of the property being measured; and 3) the mathematical properties of the data. Consideration of such aspects facilitates the choice of clinical scales and the interpretation of data.

A Compound Heterozygous Pathogenic Variant in B4GALNT1 Is Associated With Axonal Charcot-Marie-Tooth Disease

Background@#and PurposePathogenic variants in B4GALNT1 have been reported to cause hereditary spastic paraplegia 26. This study has revealed that a novel compound heterozygous pathogenic variant in B4GALNT1 is associated with axonal Charcot-Marie-Tooth disease (CMT). @*Methods@#Whole-exome sequencing (WES) was used to identify the causative factors and characterize the clinical features of a Korean family with sensorimotor polyneuropathy. Functional assessment of the mutant genes was performed using a motor neuron cell line. @*Results@#The WES revealed a compound heterozygous pathogenic variant (c.128dupC and c.451G>A) in B4GALNT1 as the causative of the present patient, a 53-year-old male who presented with axonal sensorimotor polyneuropathy and cognitive impairment without spasticity. The electrodiagnostic study showed axonal sensorimotor polyneuropathy. B4GALNT1 was critical to the proliferation of motor neuron cells. The compensation assay revealed that the pathogenic variants might affect the enzymatic activity of B4GALNT1. @*Conclusions@#This study is the first to identify a case of autosomal recessive axonal CMT associated with a compound heterozygous pathogenic variant in B4GALNT1. This finding expands the clinical and genetic spectra of peripheral neuropathy.

Clinical Features and Brain MRI Findings in Korean Patients with AGel Amyloidosis

Purpose@#AGel amyloidosis is systemic amyloidosis caused by pathogenic variants in the GSN gene. In this study, we sought to characterize the clinical and brain magnetic resonance image (MRI) features of Korean patients with AGel amyloidosis. @*Materials and Methods@#We examined 13 patients with AGel amyloidosis from three unrelated families. Brain MRIs were performed in eight patients and eight age- and sex-matched healthy controls. Therein, we analyzed gray and white matter content using voxel-based morphometry (VBM), tract-based spatial statistics (TBSS), and FreeSurfer. @*Results@#The median age at examination was 73 (interquartile range: 64–76) years. The median age at onset of cutis laxa was 20 (interquartile range: 15–30) years. All patients over that age of 60 years had dysarthria, cutis laxa, dysphagia, and facial palsy. Two patients in their 30s had only mild cutis laxa. The median age at dysarthria onset was 66 (interquartile range: 63.5–70) years. Ophthalmoparesis was observed in three patients. No patient presented with muscle weakness of the limbs. Axial fluid-attenuated inversion recovery images of the brain showed no significant differences between the patient and control groups. Also, analysis of VBM, TBSS, and FreeSurfer revealed no significant differences in cortical thickness between patients and healthy controls at the corrected significance level. @*Conclusion@#Our study outlines the clinical manifestations of prominent bulbar palsy and early-onset cutis laxa in 13 Korean patients with AGel amyloidosis and confirms that AGel amyloidosis mainly affects the peripheral nervous system rather than the central nervous system.

Rhino-orbito-cerebral Actinomycosis Infection

Purpose@#To report a case of actinomycosis infection originating in the orbitonasal cavity that quickly invaded the cerebrum.Case summary: A-57-year-old male with a history of right tooth extraction 7 days before the first visit presented with right eyelid swelling and pain that had developed 4 days prior to the visit and had become increasingly worse. The best-corrected visual acuity was light perception. The intraocular pressure of the patient was 37 mmHg in the right eye. Eyelid abscess, subconjunctival hemorrhage, and severe chemosis was observed. Orbital computed tomography showed multiple air pockets and enhancing soft tissue along the periorbital, maxillary, and ethmoid sinus. Emergent endoscopic sinus surgery, lateral canthotomy, and intravenous antifungal treatment were performed due to suspicion of mucormycosis infection. Two days after treatment, exenteration combined with otolaryngology and neurosurgery were performed, as brain magnetic resonance imaging scans indicated that intraorbital lesions had invaded the dura and frontal sinus. On Day 8 of treatment, Actinomyces odontolyticus was identified and intravenous Ampicillin was administered. Despite systemic antibiotic treatment, the infection could not be controlled. The patient died 28 days after treatment due to persistent intracranial hemorrhage and brain edema. @*Conclusions@#For patients with severe eyelid swelling with a history of tooth extraction, actinomycosis infection should be considered. Delays in diagnosis and treatment of this infection could lead to serious consequences.

Clinical Scales for the Evaluation of Myopathy Patients

With the rapid increase in the number of clinical trials in myopathy over the past decade, there is an increasing need for clinical scales to reflect patient’s clinical status. This article outlines the process of identifying possible measures. Detailed consideration has been given to key measures of muscle strength, function, and disability. As well as the usual assessment of the validity and reliability of the measures, three key characteristics were identified as necessary to the assessment of clinical scales used in health care: 1) the type of scale; 2) the clinical significance of the property being measured; and 3) the mathematical properties of the data. Consideration of such aspects facilitates the choice of clinical scales and the interpretation of data.

A Compound Heterozygous Pathogenic Variant in B4GALNT1 Is Associated With Axonal Charcot-Marie-Tooth Disease

Background@#and PurposePathogenic variants in B4GALNT1 have been reported to cause hereditary spastic paraplegia 26. This study has revealed that a novel compound heterozygous pathogenic variant in B4GALNT1 is associated with axonal Charcot-Marie-Tooth disease (CMT). @*Methods@#Whole-exome sequencing (WES) was used to identify the causative factors and characterize the clinical features of a Korean family with sensorimotor polyneuropathy. Functional assessment of the mutant genes was performed using a motor neuron cell line. @*Results@#The WES revealed a compound heterozygous pathogenic variant (c.128dupC and c.451G>A) in B4GALNT1 as the causative of the present patient, a 53-year-old male who presented with axonal sensorimotor polyneuropathy and cognitive impairment without spasticity. The electrodiagnostic study showed axonal sensorimotor polyneuropathy. B4GALNT1 was critical to the proliferation of motor neuron cells. The compensation assay revealed that the pathogenic variants might affect the enzymatic activity of B4GALNT1. @*Conclusions@#This study is the first to identify a case of autosomal recessive axonal CMT associated with a compound heterozygous pathogenic variant in B4GALNT1. This finding expands the clinical and genetic spectra of peripheral neuropathy.

Two Cases of Facioscapulohumeral Muscular Dystrophy 2 in Korea

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant muscular disorder characterized by weakness of facial, shoulder, abdominal, hip girdle, humeral, and anterior distal leg muscles, with descending progression from the face to the legs in an asymmetric pattern. In about 5% of patients with FSHD, no D4Z4 repeat contraction on chromosome 4q35 is observed;this disease entity is called FSHD2. FSHD2 is characterized by DNA hypomethylation on the 4q-subtelomeric macrosatellite repeat array D4Z4. In Korea, there have been no previous reports of FSHD2. We report the first two cases of FSHD2 in Korea, carrying c.3801delG and c.1580C>T mutations in the SMCHD1 gene, respectively. For rapid and accurate diagnosis of FSHD2, genetic analysis of the D4Z4 haplotype and methylation with next-generation sequencing are required.

Posterior condylar offset changes and its effect on clinical outcomes after posteriorsubstituting, fixed-bearing total knee arthroplasty: anterior versus posterior referencing

Background@#We sought to determine whether there was a difference in the posterior condylar offset (PCO), posterior condylar offset ratio (PCOR) and clinical outcomes following total knee arthroplasty (TKA) with anterior referencing (AR) or posterior referencing (PR) systems. We also assessed whether the PCO and PCOR changes, as well as patient factors were related to range of motion (ROM) in each referencing system. @*Methods@#This retrospective study included 130 consecutive patients (184 knees) with osteoarthritis who underwent primary posterior cruciate ligament (PCL)-substituting fixed-bearing TKA. The difference between preoperative and postoperative PCO and PCOR values were calculated. Clinical outcomes including ROM and Western Ontario and McMaster University (WOMAC) scores were evaluated. Furthermore, multiple linear regression analysis was performed to determine the factors related to postoperative ROM in each referencing system. @*Results@#The postoperative PCO was greater in the AR group (28.4 mm) than in the PR group (27.4 mm), whereas the PCO was more consistently preserved in the PR group. The mean postoperative ROM after TKA was greater in the AR group (129°) than in the PR group (122°), whereas improvement in WOMAC score did not differ between the two groups. Preoperative ROM was the only factor related to postoperative ROM in both groups. @*Conclusions@#There was no difference in postoperative PCO in AR and PR group and the PCO was not associated with postoperative ROM. PCO was more consistently preserved after surgery in the PR group. The postoperative PCO and PCOR changes did not affect the postoperative ROM. Furthermore, similar clinical outcomes were achieved in the AR and PR groups.

Incidence and Risk Factors for the Ptosis after Trabeculectomy

Purpose@#To investigate the incidence and risk factors for the ptosis after trabeculectomy. @*Methods@#We retrospectively analyzed the medical records of 94 patients who underwent trabeculectomy by a single surgeon. Patients with previous eyelid surgery and ophthalmic surgery, as well as those with systemic disease affecting the eyelid, were excluded from the study. Ptosis was defined as higher eyelid crease compared with contralateral eyelid or a ≥2 mm reduction of margin reflex distance-1 after the surgery. Age, sex, bleb location, conjunctival incision site, mitomycin C concentration, range of mitomycin C contact area, and soaking time were analyzed. @*Results@#The incidence of ptosis was 19.1% (18/94) at 6 months after trabeculectomy. There were no statistically significant relationships between postoperative ptosis and the following factors: age, sex, surgical site, bleb site, and conjunctival incision site. The incidence of ptosis was significantly higher in the 0.04% mitomycin C group than in the 0.02% mitomycin C group (40.0% vs 11.6%, p = 0.002). The incidence of ptosis was significantly higher in eyes with a large contact area of mitomycin C to the posterior part of the eye, compared to eyes with a smaller contact area (44.4% vs 9.0%, p < 0.001). Logistic regression analysis showed that the range of mitomycin C contact area remained statistically significant. @*Conclusions@#The large contact area of mitomycin C to the posterior part of the eye during trabeculectomy was found to be a risk factor for postoperative ptosis.

Effectiveness of the Tear Varicella Zoster Virus Polymerase Chain Reaction inHerpes Zoster Ophthalmicus

Purpose@#To determine the efficacy of tear varicella zoster virus polymerase chain reaction (VZV PCR) results for the occurrenceof ocular symptoms in patients diagnosed with herpes zoster ophthalmicus (HZO), as compared to Hutchinson’s sign, and to determinethe relationship between recurrence of HZO and VZV PCR results. @*Methods@#We conducted a retrospective analysis using medical records from 69 patients diagnosed with HZO from February2015 to June 2018. We investigated whether Hutchinson’s sign and VZV PCR results were correlated with the occurrence of ocularsymptoms and recurrence of HZO. @*Results@#Of the 69 patients, 51 patients (73%) had ocular symptoms and 45 patients (65.2%) had conjunctivitis as the most commonocular symptom. There were correlations between Hutchinson’s sign and the occurrence of ocular symptoms, and betweenVZV PCR and the occurrence of ocular symptoms (p = 0.047 and p = 0.005, respectively). The receiver operating characteristiccurve of Hutchinson’s sign and VZV PCR in ocular involvement of the area under the curve of the tear VZV PCR was larger thanHutchinson’s sign (VZV PCR = 0.72; Hutchinson’s sign = 0.63). Only keratouveitis was identified as a risk factor for recurrenceof HZO (odds ratio = 30.53; p = 0.033). There was no correlation between keratouveitis and recurrence of HZO (p > 0.05). @*Conclusions@#In patients with HZO, the tear VZV PCR may be as effective a predictor of ocular involvement as Hutchinson’s sign,and keratouveitis diagnosed at the initial visit was associated with the recurrence of HZO.

A Family of Congenital Fiber Type Disproportion with Mutation in Tropomyosin 3 (TPM3) Gene Presenting as Altered Mentality with Respiratory Distress

Congenital fiber type disproportion (CFTD) has been related with mutations in ACTA1, SEPN1, RYR1 and tropomyosin 3 (TPM3) genes. Particularly, TPM3 mutation was identified as one of the most frequent cause of CFTD and was also detected in cap myopathy and nemaline myopathy. Herein we report patients of autosomal dominant TPM3 missense mutations with CFTD in a Korean family over twogenerations. Two of our patients, who developed mild muscle weakness in infancy, presented with altered mentality and respiratory distress despite relatively mild limb weakness.