Involvement Of Facial Muscles Research Articles

Clinical and neurophysiological characterization of p.Gly59Ser mutation in DCTN1: a study in a Thai family and a brief review.

Mutations in the Dynactin 1 (DCTN1) gene lead to various neurodegenerative disorders. The p.Gly59Ser mutation, the first pathogenic mutation identified in DCTN1, was initially reported in a family with distal hereditary motor neuropathy and early vocal cord paralysis. Since its discovery in 2003, this mutation has been documented in only three families worldwide, to the best of our knowledge. This study examines six patients from a Thai family carrying the p.Gly59Ser mutation in DCTN1 and includes a literature review. Five of the patients were female. The mean age of onset was 32.6 ± 1.9 years. Thai patients showed early involvement of intrinsic hand, facial, and bulbar muscles, with vocal cord impairment manifesting later in the disease course. Tongue fasciculations, not previously reported with this mutation, were observed in most Thai patients. Bilateral split-hands were consistently noted. Arytenoidectomy and cordotomy have proven beneficial in relieving upper airway obstruction and preventing life-threatening upper airway complications from vocal cord paralysis. The p.Gly59Ser mutation in DCTN1 presents with autosomal-dominant, adult-onset, lower motor neuronopathy/neuropathy. Compared to earlier reports, Thai patients exhibited more widespread involvement, including facial, bulbar, tongue, vocal cord, and limb muscles. In addition to vocal cord paralysis, the split-hand phenomenon emerges as another clinical hallmark of this condition.

ANO10-Related Spinocerebellar Ataxia: MDSGene Systematic Literature Review and a Romani Case Series.

Biallelic pathogenic variants in the ANO10 gene cause autosomal recessive progressive ataxia (ATX-ANO10). Following the MDSGene protocol, we systematically investigated genotype-phenotype relationships in ATX-ANO10 based on the clinical and genetic data from 82 published and 12 newly identified patients. Most patients (>80%) had loss-of-function (LOF) variants. The most common variant was c.1150_1151del, found in all 29 patients of Romani ancestry, who had a 14-year earlier mean age at onset than patients homozygous for other LOF variants. We identified previously undescribed clinical features of ATX-ANO10 (e.g., facial muscle involvement and strabismus) suggesting the involvement of brainstem pathology, and we propose a diagnostic algorithm that may aid clinical ATX-ANO10 diagnosis. The early disease onset in patients with c.1150_1151del may indicate the existence of genetic/environmental disease-modifying factors in the Romani population. Our findings will inform patient counseling and may improve our understanding of the disease mechanism. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

The effect of myotonic dystrophy type 1 on temporomandibular joint and dentofacial morphology: A CBCT analysis.

Myotonic dystrophy type 1 (DM1) is a neuromuscular multisystem disease. Early involvement of facial muscles may produce an extra load on the temporomandibular joint (TMJ) in DM1. This study aimed to investigate the morphological analyses of the bone components of temporomandibular joint (TMJ), and dentofacial morphology in myotonic dystrophy type 1 (DM1) patients by cone-beam computed tomography (CBCT). Sixty-six individuals (33 DM1, and 33 healthy subjects) age ranging from 20 to 69 were included in the study. Clinical examinations of the patients' TMJ regions and evaluation of dentofacial morphology (maxillary deficiency, open-bite, deep palate and cross-bite) were performed. Dental occlusion was determined based on Angle's classification. CBCT images were evaluated regarding mandibular condyle morphology (convex, angled, flat and round) and osseous changes observed in the condyle (normal, osteophyte, erosion, flattening, sclerosis). DM1-specific morphological and bony TMJ alterations were determined. DM1 patients showed a high prevalence of morphological and osseous TMJ changes, and statistically significant skeletal alterations. The analysis of CBCT scans indicated the prevalent condylar shape among patients with DM1 was flat, the main osseous abnormality was flattening, there was a tendency towards skeletal Class II and a posterior cross-bite was frequently detected in DM1 patients. There was no statistically significant difference between the genders on the parameters evaluated in both groups. Adult patients with DM1 presented a high frequency of crossbite, tendency to skeletal Class II and morphological osseous alterations of TMJ. The analysis of the morphological condylar alterations in patients with DM1 may be beneficial in the diagnosis of TMJ disorders. This study reveals DM1-specific morphological and osseous TMJ alterations to provide an appropriate orthodontic/orthognathic treatment planning to patients.

Facial nerve vulnerability in spinal muscular atrophy and motor unit number index of the orbicularis oculi muscle.

Measures for assessing cranial nerve vulnerability in spinal muscular atrophy (SMA) have not yet been determined. Motor unit number index (MUNIX) studies have shown correlations with disease severity but have been used only in limb muscles. In the present study, we explore facial nerve response, MUNIX, and motor unit size index (MUSIX) of the orbicularis oculi muscle in a cohort of patients with SMA. Facial nerve response (measured as compound muscle action potential, CMAP), MUNIX, and MUSIX of the orbicularis oculi muscle were cross-sectionally recorded in patients with SMA and compared to healthy control subjects (HCs). Active maximum mouth opening (aMMO) was also measured at baseline in our SMA cohort. Thirty-seven patients with SMA (21 SMA II; 16 SMA III) and 27 HCs were recruited. CMAP of the facial nerve and MUNIX of orbicularis oculi proved to be feasible and well tolerated techniques. CMAP amplitude and MUNIX scores were significantly lower in patients with SMA compared to HCs (p < .0001). Both MUNIX and CMAP amplitude were significantly higher in patients with SMA III compared to SMA II. No significant difference emerged comparing CMAP amplitude, MUNIX and MUSIX scores between those with different functional status or nusinersen treatment. Our results provide neurophysiological evidence of facial nerve and muscle involvement in patients with SMA. CMAP of the facial nerve and MUNIX of orbicularis oculi showed high accuracy in discriminating between the various subtypes of SMA and in quantifying the motor unit loss of the facial nerve.

Editors' Note: Teaching Video NeuroImage: Bilateral Hemifacial Spasm in Giant Cell Arteritis.

In “Teaching Video NeuroImage: Bilateral Hemifacial Spasm in Giant Cell Arteritis,” Sechi et al. presented a video of bilateral hemifacial spasm in a patient with giant cell arteritis complicated by supratentorial infarcts. They attributed the facial contractions to facial nerve irritation. However, because the orbicularis and frontalis contraction occurred bilaterally and simultaneously, Cornblath and Eggenberger suggested it appeared to be centrally mediated and proposed it could be an epileptic phenomenon associated with the supratentorial infarcts. Sechi et al. responded that their patient (1) had asymmetric cheek movements characteristic of bilateral hemifacial spasm; (2) had exclusive involvement of upper facial muscles, consistent with peripheral irritation of the superior branch of the facial nerve; (3) improved with steroids (and was not given antiepileptic drugs); (4) had a normal EEG (although this was performed after the resolution of the facial contractions); and (5) had no recurrence of facial contractions in the subsequent 4 years. While it seems unlikely that the superior branches of the facial nerve would simultaneously be activated bilaterally, the rapid resolution and absence of recurrence of this patient's bilateral hemifacial spasm makes the etiology unclear. In “Teaching Video NeuroImage: Bilateral Hemifacial Spasm in Giant Cell Arteritis,” Sechi et al. presented a video of bilateral hemifacial spasm in a patient with giant cell arteritis complicated by supratentorial infarcts. They attributed the facial contractions to facial nerve irritation. However, because the orbicularis and frontalis contraction occurred bilaterally and simultaneously, Cornblath and Eggenberger suggested it appeared to be centrally mediated and proposed it could be an epileptic phenomenon associated with the supratentorial infarcts. Sechi et al. responded that their patient (1) had asymmetric cheek movements characteristic of bilateral hemifacial spasm; (2) had exclusive involvement of upper facial muscles, consistent with peripheral irritation of the superior branch of the facial nerve; (3) improved with steroids (and was not given antiepileptic drugs); (4) had a normal EEG (although this was performed after the resolution of the facial contractions); and (5) had no recurrence of facial contractions in the subsequent 4 years. While it seems unlikely that the superior branches of the facial nerve would simultaneously be activated bilaterally, the rapid resolution and absence of recurrence of this patient's bilateral hemifacial spasm makes the etiology unclear.

NOTCH2NLC-related oculopharyngodistal myopathy type 3 complicated with focal segmental glomerular sclerosis: a case report

BackgroundOculopharyngodistal myopathy (OPDM) is an adult-onset neuromuscular disease characterized by progressive ocular, facial, pharyngeal, and distal limb muscle involvement. Recent research showed that GGC repeat expansions in the NOTCH2NLC gene were observed in a proportion of OPDM patients, and these patients were designated as having OPDM type 3 (OPDM3). Heterogeneous neuromuscular manifestations have been described previously in studies of OPDM3; however, kidney involvement in this disease has rarely been reported.Case presentationHere, we report the case of a 22-year-old Chinese patient with typical manifestations of OPDM complicated with focal segmental glomerular sclerosis (FSGS). This patient with sporadic FSGS exhibited distal motor neuropathy and rimmed vacuolar myopathy in clinical and pathological examinations. An expansion of 122 CGG repeats located in the 5’ untranslated region (UTR) of the NOTCH2NLC gene was identified as the causative mutation in this patient. The clinical and histopathological findings fully met the criteria for the diagnosis of OPDM3. In addition, intranuclear inclusions were detected in the renal tubule epithelial cells of this patient, indicating that the kidney may also be impaired in NOTCH2NLC-related GGC repeat expansion disorders (NREDs).ConclusionsOur case report demonstrated the clinicopathological cooccurrence of sporadic FSGS and OPDM3 in a patient, which highlighted that the kidney may show inclusion depositions in OPDM3, thus expanding the clinical spectrum of NREDs.

GFPT1-Associated Congenital Myasthenic Syndrome Mimicking a Glycogen Storage Disease - Diagnostic Pitfalls in Myopathology Solved by Next-Generation-Sequencing.

GFPT1-related congenital myasthenic syndrome (CMS) is characterized by progressive limb girdle weakness, and less prominent involvement of facial, bulbar, or respiratory muscles. While tubular aggregates in muscle biopsy are considered highly indicative in GFPT1-associated CMS, excessive glycogen storage has not been described. Here, we report on three affected siblings with limb-girdle myasthenia due to biallelic pathogenic variants in GFPT1: the previously reported missense variant c.41G > A (p.Arg14Gln) and the novel truncating variant c.1265_1268del (p.Phe422TrpfsTer26). Patients showed progressive proximal atrophic muscular weakness with respiratory involvement, and a lethal disease course in adulthood. In the diagnostic workup at that time, muscle biopsy suggested a glycogen storage disease. Initially, Pompe disease was suspected. However, enzymatic activity of acid alpha-glucosidase was normal, and gene panel analysis including 38 genes associated with limb-girdle weakness (GAA included) remained unevocative. Hence, a non-specified glycogen storage myopathy was diagnosed. A decade later, the diagnosis of GFPT1-related CMS was established by genome sequencing. Myopathological reexamination showed pronounced glycogen accumulations, that were exclusively found in denervated muscle fibers. Only single fibers showed very small tubular aggregates, identified in evaluation of serial sections. This family demonstrates how diagnostic pitfalls can be addressed by an integrative approach including broad genetic analysis and re-evaluation of clinical as well as myopathological findings.

Asymmetrical scapular winging, bilateral facial muscle involvement and distal myopathy with normal CPK; unusual features in anti JO-I positive polymyositis

Introduction Polymyositis is an idiopathic inflammatory myopathy which present with typical symmetrical proximal muscle weakness with the evidence of muscle inflammation. The acute inflammation of muscle results in high levels of CPK and has a relapsing remitting course with a good response to anti-inflammatory treatment. We present here a patient presented with a chronic myopathy with relapsing remitting fashion, with asymmetrical scapula winging, and bilateral facial weakness, with predominant distal muscle weakness which was supported by EMG.

The GGC repeat expansion in NOTCH2NLC is associated with oculopharyngodistal myopathy type 3.

Oculopharyngodistal myopathy (OPDM) is an adult-onset neuromuscular disease characterized by progressive ocular, facial, pharyngeal and distal limb muscle involvement. Trinucleotide repeat expansions in LRP12 or GIPC1 were recently reported to be associated with OPDM. However, a significant portion of OPDM patients have unknown genetic causes. In this study, long-read whole-genome sequencing and repeat-primed PCR were performed and we identified GGC repeat expansions in the NOTCH2NLC gene in 16.7% (4/24) of a cohort of Chinese OPDM patients, designated as OPDM type 3 (OPDM3). Methylation analysis indicated that methylation levels of the NOTCH2NLC gene were unaltered in OPDM3 patients, but increased significantly in asymptomatic carriers. Quantitative real-time PCR analysis indicated that NOTCH2NLC mRNA levels were increased in muscle but not in blood of OPDM3 patients. Immunofluorescence on OPDM muscle samples and expressing mutant NOTCH2NLC with (GGC)69 repeat expansions in HEK293 cells indicated that mutant NOTCH2NLC-polyglycine protein might be a major component of intranuclear inclusions, and contribute to toxicity in cultured cells. In addition, two RNA-binding proteins, hnRNP A/B and MBNL1, were both co-localized with p62 in intranuclear inclusions in OPDM muscle samples. These results indicated that a toxic protein gain-of-function mechanism and RNA gain-of-function mechanism may both play a vital role in the pathogenic processes of OPDM3. This study extended the spectrum of NOTCH2NLC repeat expansion-related diseases to a predominant myopathy phenotype presenting as OPDM, and provided evidence for possible pathogenesis of these diseases.

Latency of Spread: An Important Clinical Indicator Reflecting the Complexity Level of Offending Vessels in Patients with Typical Hemifacial Spasm.

To investigate whether the latency of spread could reflect the complexity level of intraoperative offending vessels in patients with typical hemifacial spasm. A total of 96 patients with typical hemifacial spasm who underwent microvascular decompression (MVD) in our department between August 2018 and December 2019 were retrospectively analyzed. We introduced a new concept of three complexity levels of offending vessels based on six vascular classifications proposed by Kwan Park et al. and the difficulty of intraoperative management reviewed by surgical videos. One-way analysis of variance, Spearman correlation analysis, and multivariate linear regression analysis were performed. There were significant differences in latency of spread among the three complexity levels of offending vessels (p < 0.01). Spearman correlation analysis showed a strong negative correlation between vascular complexity level and the latency of spread (r=-0.7997, p < 0.0001). Multivariate linear regression analysis showed that the vascular complexity level was the main factor affecting the latency of spread (p < 0.01). In contrast, other factors such as sex, side, age, hypertension, and diabetes had no significant effects. The latency of spread, as an important clinical indicator, can reflect the complexity level of offending vessels in patients with typical hemifacial spasm before MVD.

Anaesthesia and orphan disease: A patient with neuromyotonia undergoing single lung ventilation.

Anaesthesia and orphan disease: A patient with neuromyotonia undergoing single lung ventilation.

Effects of weakness of orofacial muscles on swallowing and communication in FSHD.

This study explores the use of quantitative data on strength and fatigability of orofacial muscles in patients with facioscapulohumeral muscular dystrophy (FSHD) and assesses the frequency of swallowing and communication difficulties and their relationship to orofacial muscle involvement. We included 43 patients with FSHD and 35 healthy controls and used the Iowa Oral Performance Instrument (IOPI) to obtain quantitative measurements of strength and endurance of lip compression, cheek (buccodental) compression, and tongue elevation. For the assessment of swallowing and communication difficulties, we used the dysphagia-specific quality of life (SWAL-QOL) and Communicative Participation Item Bank questionnaires. Cheek compression strength was reduced in patients with FSHD compared to healthy controls. Dysphagia and difficulty with verbal communication were reported by 25% and 35% of patients, respectively, and correlated to cheek compression strength and endurance and to anterior tongue elevation endurance. Prolonged cheek compression or anterior tongue elevation endurance (decreased fatigability) made swallowing or speech problems less likely to occur. Cheek compression strength is the most sensitive IOPI measure for orofacial weakness in FSHD. Orofacial weakness contributes to dysphagia and speech difficulties in FSHD, which are both common, though generally mild. Higher endurance of orofacial muscles was associated with a lower chance of dysphagia or speech problems. More research is required for further refinement of the pattern of facial muscle involvement in FSHD and to provide new insights for improvement of speech and language therapy.

Phenotype-genotype relations in facioscapulohumeral muscular dystrophy type 1.

To determine how much of the clinical variability in facioscapulohumeral muscular dystrophy type 1 (FSHD1) can be explained by the D4Z4 repeat array size, D4Z4 methylation and familial factors, we included 152 carriers of an FSHD1 allele (23 single cases, 129 familial cases from 37 families) and performed state-of-the-art genetic testing, extensive clinical evaluation and quantitative muscle MRI. Familial factors accounted for 50% of the variance in disease severity (FSHD clinical score). The explained variance by the D4Z4 repeat array size for disease severity was limited (approximately 10%), and varied per body region (facial muscles, upper and lower extremities approximately 30%, 15% and 3%, respectively). Unaffected gene carriers had longer repeat array sizes compared to symptomatic individuals (7.3 vs 6.0 units, P = 0.000) and slightly higher Delta1 methylation levels (D4Z4 methylation corrected for repeat size, 0.96 vs -2.46, P = 0.048). The D4Z4 repeat array size and D4Z4 methylation contribute to variability in disease severity and penetrance, but other disease modifying factors must be involved as well. The larger effect of the D4Z4 repeat array on facial muscle involvement suggests that these muscles are more sensitive to the influence of the FSHD1 locus itself, whereas leg muscle involvement seems highly dependent on modifying factors.

Electromyography: Beyond positive diagnosis of myastenic syndrome

Objectives Electromyography (EMG) plays a major role to confirm the presence of neuromuscular transmission disorders. Furthermore, it helps to recognize the presynaptic or postsynaptic nature of the disorder. Indeed, specialized neurophysiological tests and characteristic electrophysiological findings are widely useful for etiological diagnosis [1] , [2] . Results Here we report two cases, a 36 years-old woman and 37 years-old men who presented to our department for facial muscle weakness. The female presented for drooping of both eyelids with diplopia, which appears while reading. Neurological examination showed bilateral asymmetric ptosis and complete ophtalmoplegia. Pupillary light reflex was normal as well as the rest of the neurological examination. The neostigmine test was positive. Repetitive nerve stimulation (RNS) testat 3 Hz stimulation, showed a significant decremental response in both area and amplitude with repetitive compound muscle action potentials (R-CMAP). Muscle biopsy eliminated centro-nuclear myopathy. We then considered the diagnosis of postsynaptic congenital myasthenic syndrome. The man presented with a ten days history of facial muscle weakness, dysphonia and swallowing disorders without diurnal fluctuation. Neurological examination noted symmetric proximal limb weakness. Clinical picture was concordant with acute inflammatory demyelinating polyradiculoneuropathy. Lumbar puncture did not evidence albumino-cytologic dissociation. Electrodiagnostic studies demonstrated a reduction in the initial CMAP amplitude, a decremental response to slow stimulation rates (3 Hz), followed by incremental response after a tetanic stimulation consistant with Lambert Eaton Syndrome. Conclusion In general, full anamnestic data and careful clinical examination are sufficient to make the diagnosis of myastenic syndrome. Nevertheless, the lack of diurnal fluctuation and a clear pattern of muscle distribution can sometimes lead to misdiagnosing this disorder [2] , [3] . Moreover, myastenic syndrome with predominant facial muscle involvement share overlapping symptoms with other muscle disease like mitochondrial and centro-nuclear myopathy. These findings delineate the contribution of EMG to differential and etiologic diagnosis [1] .

Ophthalmic manifestations of facial nerve palsy

Facial nerve palsy is a common pathology that develops due to various diseases, traumas and medical interventions. The most common peripheral type of facial paralysis leads to acute unilateral involvement of facial muscles along with the development of paralytic lagophthalmos. The absence of adequate and timely medical treatment in patients with paralytic lagophthalmos can lead to severe corneal complications such as cornea perforation causing loss of eye and consequently restricted professional ability, work capacity and significant decrease of patient's life quality. Patients with paralytic lagophthalmos require timely, complex, planned treatment involving various correction methods aimed at protection of the cornea, as well as anatomical and functional recovery of the eyelids. Chemodenervation of the upper eyelid muscles is a pathogenetically substantiated method that can help restore the protective function of the upper eyelid and prevent corneal complications; it can be recommended for early stages of the disease.

Telemedicine for Facio-Scapulo-Humeral Muscular Dystrophy: A multidisciplinary approach to improve quality of life and reduce hospitalization rate?

BackgroundFacio-Scapulo-Humeral Muscular Dystrophy (FSHD) is an autosomal dominant inherited disorder characterized by a variable and asymmetric involvement of facial, trunk, upper and lower extremity muscles. Although respiratory weakness is a relatively unknown feature of FSHD, it is not rare. Telemedicine has been used in a variety of health care fields, but only recently, with the advent of sophisticated technology, its interest among health professionals became evident, even in such diseases. ObjectiveTo demonstrate the telemedicine efficacy in FSHD. MethodsFour siblings affected by a severe form of FSHD, living in a rural area far away from the referral center for neuromuscular diseases, who used a wheelchair, suffered from chronic respiratory failure and were provided with long-term non-invasive mechanical ventilation, received a 6-month period of telemedicine support. This consisted of video conferencing (respiratory physiotherapy, psychological support, neurological and pneumological assessment, nurse-coach supervision) and telemonitoring of cardiorespiratory variables (oxygen saturation, blood pressure, and heart rate). ResultsWe performed 540 video conference sessions per patient, including three daily contacts with short monitoring oximetry measurements, blood pressure, and heart-rate measurements, psychological support, neurological and pneumological assessment, nurse-coach supervision. ConclusionsOur findings indicate that our telemedicine system was user-friendly, efficient for the home treatment of FSHD, and allowed reducing hospital admissions.

A case of juvenile polymyositis post viral hepatitis A

Polymyositis is rare as a stand-alone entity and is often misdiagnosed; most patients whose condition has been diagnosed as polymyositis have inclusion-body myositis, necrotizing autoimmune myositis, or inflammatory dystrophy. Polymyositis remains a diagnosis of exclusion and is best defined as a subacute proximal myopathy in adults who do not have rash, a family history of neuromuscular disease, exposure to myotoxic drugs (e.g. statins, penicillamine, and zidovudine), involvement of facial and extraocular muscles, endocrinopathy, or the clinical phenotype of inclusion body myositis. The etiology of polymyositis may be due to underlying systemic autoimmune diseases, viral, parasitic, bacterial infections or drug induced. Here we describe a case of juvenile polymyositis post viral infection with hepatitis A.

A novel MYH2 mutation in family members presenting with congenital myopathy, ophthalmoplegia and facial weakness.

Myosin heavy chain (MyHC) is a major structural component of the striated muscle contractile apparatus. In adult human limb skeletal muscle, there are three major MyHC isoforms, slow/beta cardiac MyHC, MyHC IIa and MHC IIx, which are important for the functional characteristics of different muscle fiber types. Hereditary myosin myopathies have emerged as an important group of diseases with variable clinical and morphological expression dependent on the mutated isoform, and also the type and location of the mutation. Myosin myopathy with external ophthalmoplegia is associated with mutations in MYH2, encoding for MyHC IIa that is mainly expressed in type 2A muscle fibers and is inherited in dominant as well as recessive manner. We present a family with myopathy with early onset proximal muscle weakness, facial muscle involvement and ophthalmoplegia. Muscle biopsy demonstrated lack of type 2A muscle fibers and genetic work up demonstrated that the disease was caused by a novel recessive MYH2 mutation: c.1009-1G>A resulting in skipping of exon 12, which is predicted to result in a frame shift and introducing at premature stop codon at position 347 (p.Ser337Leufs*11).

Clinical, pathological and genetic characteristics of autosomal dominant inherited dynamin2 centronuclear myopathy.

The aim of the present study was to report on a family with pathologically and genetically diagnosed autosomal dominant inherited centronuclear myopathy (CNM). In addition, this study aimed to investigate the clinical, pathological and molecular genetic characteristics of the disease. This pedigree was traced back three generations, four patients underwent neurological examination, two patients underwent muscle biopsy, and eight family members were subjected to dynamin2 (DNM2) gene mutation analysis. DNM2 mutations were detected in seven family members, of which four patients exhibited DNM2 mutation‑specific clinical and pathological features. Lower extremity weakness was the predominant symptom of these patients, however, proximal and distal lower extremity involvement was inconsistent. All patients exhibited marked systematic muscle atrophy and various degrees of facial muscle involvement. The patients presented the typical pathological changes of CNM, and their muscle tissues were heavily replaced by adipose tissue, with clustered distribution of muscle fibers as another notable feature. DNM2‑CNM patients of this pedigree exhibited heterogeneous clinical and pathological features, providing a basis for further molecular genetic analysis.

Mild Clinical Features and Histopathologically Atypical Cores in Two Korean Families with Central Core Disease HarboringRYR1Mutations at the C-Terminal Region

BackgroundCentral core disease (CCD) is a congenital myopathy characterized by distinctive cores in muscle fibers. Mutations in the gene encoding ryanodine receptor 1 (RYR1) have been identified in most CCD patients.Case ReportTwo unrelated patients presented with slowly progressive or nonprogressive proximal muscle weakness since childhood. Their family history revealed some members with the same clinical problem. Histological analysis of muscle biopsy samples revealed numerous peripheral cores in the muscle fibers. RYR1 sequence analysis disclosed a novel mutation in exon 101 (c.14590T>C) and confirmed a previously reported mutation in exon 102 (c.14678G>A).ConclusionsWe report herein two families with CCD in whom missense mutations at the C-terminal of RYR1 were identified. Although it has been accepted that such mutations are usually associated with a severe clinical phenotype and clearly demarcated central cores, our patients exhibited a mild clinical phenotype without facial muscle involvement and skeletal deformities, and atypical cores in their muscle biopsy specimens.