Molecular mechanisms of muscle atrophy in myotonic dystrophies

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Timchenko, Lubov

2013-01-01

Myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2) are multisystemic diseases that primarily affect skeletal muscle, causing myotonia, muscle atrophy, and muscle weakness. DM1 and DM2 pathologies are caused by expansion of CTG and CCTG repeats in non-coding regions of the genes encoding myotonic dystrophy protein kinase (DMPK) and Zinc finger protein 9 (ZNF9) respectively. These expansions cause DM pathologies through accumulation of mutant RNAs that alter RNA metabolism in p...

[Dystrophia myotonica (Steinert disease)--a frequently misdiagnosed disease].

Science.gov (United States)

Kuhn, E; Lehmann-Horn, F; Rüdel, R

1990-06-01

Dystrophia myotonica (Steinert's disease) is the most common hereditary disease of the neuromuscular system in adults. Its mode of inheritance is autosomal dominant. The gene responsible for its is located on chromosome 19 in the linkage domain of the loci for the apolipoproteins C2, C1 und E and of the creatine kinase of skeletal muscle (CKMM). Myotonic dystrophy is categorized in an adult and in a congenital form. In the adult form, the characteristic findings are muscular atrophy in certain regions of the body (face, neck and distally in the extremities) and myotonia. Cataract, intraocular hypotension, gonadal atrophy, conduction abnormalities in the heart and hearing deficiencies appear quite often in the course of the disease. In the congenital form, general muscle weekness (particularly pronounced in the face) is the leading finding, combined with retarded loco motor and mental development. A decisive criterion for the diagnosis of this form is the occurrence of myotonic dystrophy in the patient's mother. Electromyographic investigation is indicated when a suspicion of myotonic dystrophy cannot be ascertained on the basis of clinical and genetic findings. Myotonic runs in the EMG will then corroborate the suspicion. Recent electrophysiological investigations have indicated that at least three different types of channels for the passage of ions through the membrane of the skeletal muscle cells show abnormal behaviour, i.e. the channel for Cl-, Na+ and K+. These findings corroborate the hypothesis that the abnormality responsible for myotonic dystrophy is situated in the membrane systems. A pharmacological treatment of the muscular dystrophy has not yet been developed.(ABSTRACT TRUNCATED AT 250 WORDS)

Survey of Canadian Myotonic Dystrophy Patients' Access to Computer Technology.

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Climans, Seth A; Piechowicz, Christine; Koopman, Wilma J; Venance, Shannon L

2017-09-01

Myotonic dystrophy type 1 is an autosomal dominant condition affecting distal hand strength, energy, and cognition. Increasingly, patients and families are seeking information online. An online neuromuscular patient portal under development can help patients access resources and interact with each other regardless of location. It is unknown how individuals living with myotonic dystrophy interact with technology and whether barriers to access exist. We aimed to characterize technology use among participants with myotonic dystrophy and to determine whether there is interest in a patient portal. Surveys were mailed to 156 participants with myotonic dystrophy type 1 registered with the Canadian Neuromuscular Disease Registry. Seventy-five participants (60% female) responded; almost half were younger than 46 years. Most (84%) used the internet; almost half of the responders (47%) used social media. The complexity and cost of technology were commonly cited reasons not to use technology. The majority of responders (76%) were interested in a myotonic dystrophy patient portal. Patients in a Canada-wide registry of myotonic dystrophy have access to and use technology such as computers and mobile phones. These patients expressed interest in a portal that would provide them with an opportunity to network with others with myotonic dystrophy and to access information about the disease.

Can long-term thiamine treatment improve the clinical outcomes of myotonic dystrophy type 1?

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Costantini, Antonio; Trevi, Erika; Pala, Maria Immacolata; Fancellu, Roberto

2016-09-01

Myotonic dystrophy type 1, also known as Steinert's disease, is an autosomal dominant disorder with multisystemic clinical features affecting the skeletal and cardiac muscles, the eyes, and the endocrine system. Thiamine (vitamin B1) is a cofactor of fundamental enzymes involved in the energetic cell metabolism; recent studies described its role in oxidative stress, protein processing, peroxisomal function, and gene expression. Thiamine deficiency is critical mainly in the central and peripheral nervous system, as well as in the muscular cells. Our aim was to investigate the potential therapeutical effects of long-term treatment with thiamine in myotonic dystrophy type 1 in an observational open-label pilot study. We described two patients with myotonic dystrophy type 1 treated with intramuscular thiamine 100 mg twice a week for 12 or 11 months. We evaluated the patients using the grading of muscle strength according to Medical Research Council (MRC), the Muscular Impairment Rating Scale (MIRS), and the Modified Barthel index. High-dose thiamine treatment was well tolerated and effective in improving the motor symptomatology, particularly the muscle strength evaluated with the MRC scale, and the patients' activities of daily living using the Modified Barthel Index. At the end of treatment, the MRC score was 5 in the proximal muscles and 2-4 in the distal muscles (the MRC score before the treatment was 3-4 and 1-3, respectively). The MIRS grade improved by 25% compared to baseline for both patients. In patient #1, the Modified Barthel Index improved by 44%, and in patient #2 by 29%. These findings suggest that clinical outcomes are improved by long-term thiamine treatment.

Pattern Dystrophy of the Macula in a Case of Steinert Disease

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Filipe Esteves

2013-09-01

Full Text Available Introduction: Myotonic dystrophies are typically associated with ocular complications like ptosis, weakness of the ocular muscle and cataracts, but also with less recognized retinal changes. Case Report: A 41-year-old female with type 1 myotonic dystrophy complained of progressive vision loss. Slit lamp examination revealed the presence of typical bilateral polychromatic cataract with posterior subcapsular component. Dilated fundus examination was remarkable for bilateral macular depigmented changes. Multimodal imaging analysis of the macula suggested the presence of a butterfly-shaped pattern dystrophy. Discussion: In cases of myotonic dystrophies it is of great relevance to analyze the presence of retinal changes that might limit the visual improvement following cataract extraction.

CONGENITAL MYOTONIC DYSTROPHY – CASE REPORT

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David Neubauer

2001-07-01

Full Text Available Background. Myotonic dystrophy is inherited as an autosomal dominant trait. It is characterized by myotonia, myopathy of voluntary and involuntary muscles, frontal baldness in men, cardiac conduction abnormalities, catharacts, intellectual deterioration and endocrinopathy. Men with this disorder have often gonadal atrophy and infertility. On the other hand women are generally fertile. During pregnancy their myopathy worsens, often causing severe obstetrical complications. Their children may develop congenital form of the disease with signs of myopathy in utero and have great difficulties in maintaining life functions after birth, together with other characteristical signs of this form: bilateral facial weakness, severe hypotonia, feeding difficulties, talipes equinovarus and mental retardation. The authors present a female newborn with such congenital form of myotonic dystrophy.Conclusions. The authors have emphasized the importance of medical history, regular updating of all the cases of neuromuscular diseases in the region and clinical characteristics for the recognition of congenital form of myotonic dystrophy because of possible prenatal diagnostics and better antenatal and postantal care.

Sleep disturbances in myotonic dystrophy type 2

OpenAIRE

Shepard, Paul; Lam, Erek M.; St. Louis, Erik K.; Dominik, Jacob

2012-01-01

Sleep disorders in myotonic dystrophy type 1 (DM1) are common and include sleep disordered breathing (SDB), hypersomnia, and fatigue. Little is known regarding the occurrence of sleep disturbance in myotonic dystrophy type 2 (DM2). We hypothesized that DM2 patients may frequently harbor sleep disorders. We reviewed medical records of all genetically confirmed cases of DM2 seen at our sleep center between 1997 and 2010 for demographic, laboratory, overnight oximetry, and polysomnography (PSG) ...

Dysphagia is present but mild in myotonic dystrophy type 2

NARCIS (Netherlands)

R. Ensink; Bert de Swart; J. van Vliet; A. Tieleman; Baziel van Engelen; S. Knuijt

2009-01-01

The phenotype of myotonic dystrophy type 2 (DM2) shows similarities as well as differences to that of myotonic dystrophy type 1 (DM1). Dysphagia, a predominant feature in DM1, has not yet been examined in DM2. In a recent nationwide questionnaire survey of gastrointestinal symptoms in DM2, 12 out of

Concurrence of myotonic dystrophy and epilepsy: a case report

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Worku, Dawit Kibru

2014-01-01

Introduction Myotonic dystrophy is a clinically and genetically heterogeneous multisystem disorder with a prevalence of 1 in 8000 in the general population. Case presentation A 25-year-old Ethiopian man presented with symptoms of myotonia, muscle wasting, gait problems, frontal baldness, and family history characterizing the hereditary disorder myotonic dystrophy. He had been on treatment for idiopathic generalized epilepsy for over 15 years. A needle electromyography showed insertional class...

Epiretinal membrane: a treatable cause of visual disability in myotonic dystrophy type 1.

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Kersten, Hannah M; Roxburgh, Richard H; Child, Nicholas; Polkinghorne, Philip J; Frampton, Chris; Danesh-Meyer, Helen V

2014-01-01

A wide range of ocular abnormalities have been documented to occur in patients with myotonic dystrophy type 1. The objectives of this study were to investigate the macular and optic nerve morphology using optical coherence tomography in patients with myotonic dystrophy type 1. A total of 30 myotonic dystrophy type 1 patients and 28 controls were recruited for participation. All participants underwent a thorough ophthalmologic examination, including spectral-domain optical coherence tomography of the macula and retinal nerve fibre layer. Images were reviewed by a retinal specialist ophthalmologist, masked to the diagnosis of the participants. Average macular thickness was significantly greater in the myotonic dystrophy group compared to controls [327.3 μm vs. 308.5 μm (p Visual acuity was reduced due to the presence of epiretinal membrane in six patient eyes and none of the control eyes. The presence of an epiretinal membrane was significantly correlated with increasing age in the patient group. We report an increased prevalence of epiretinal membrane in the myotonic dystrophy type 1 group. This may be a previously under-recognised form of visual impairment in this group. Epiretinal membranes can be treated surgically. We suggest that, in addition to a comprehensive clinical examination, optical coherence tomography examination is implemented as part of an ophthalmological assessment for the myotonic dystrophy type 1 patient with reduced visual acuity.

Aberrant Myokine Signaling in Congenital Myotonic Dystrophy

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Masayuki Nakamori

2017-10-01

Full Text Available Summary: Myotonic dystrophy types 1 (DM1 and 2 (DM2 are dominantly inherited neuromuscular disorders caused by a toxic gain of function of expanded CUG and CCUG repeats, respectively. Although both disorders are clinically similar, congenital myotonic dystrophy (CDM, a severe DM form, is found only in DM1. CDM is also characterized by muscle fiber immaturity not observed in adult DM, suggesting specific pathological mechanisms. Here, we revealed upregulation of the interleukin-6 (IL-6 myokine signaling pathway in CDM muscles. We also found a correlation between muscle immaturity and not only IL-6 expression but also expanded CTG repeat length and CpG methylation status upstream of the repeats. Aberrant CpG methylation was associated with transcriptional dysregulation at the repeat locus, increasing the toxic RNA burden that upregulates IL-6. Because the IL-6 pathway is involved in myocyte maturation and muscle atrophy, our results indicate that enhanced RNA toxicity contributes to severe CDM phenotypes through aberrant IL-6 signaling. : Congenital myotonic dystrophy (CDM manifests characteristic genetic (very large CTG repeat expansions, epigenetic (CpG hypermethylation upstream of the repeat, and phenotypic (muscle immaturity features not seen in adult DM. Nakamori et al. find phenotype-genotype and epigenotype correlation in CDM muscle and reveal involvement of the IL-6 myokine signaling pathway in the disease process. Keywords: CTCF, ER stress, IL-6, muscular dystrophy, NF-κB, trinucleotide, cytokine, splicing

Skeletal muscle CT of lower extremities in myotonic dystrophy

International Nuclear Information System (INIS)

Takahashi, Ryosuke; Imai, Terukuni; Sadashima, Hiromichi; Matsumoto, Sadayuki; Yamamoto, Toru; Kusaka, Hirofumi; Yamasaki, Masahiro; Maya, Kiyomi; Tanabe, Masaya

1988-01-01

We evaluated the leg and thigh muscles of 4 control subjects and 10 patients with myotonic dystrophy using computed tomography. Taking previous reports about the skeletal muscle CT of myotonic dystrophy into account, we concluded that the following 5 features are characteristic of myotonic dystrophy: 1. The main change is the appearance of low-density areas in muscles; these areas reflect fat tissue. In addition, the muscle mass decreases in size. 2. The leg is more severely affected than the thigh. 3. In the thigh, although the m. quadriceps femoris, especially the vastus muscles, tends to be affected, the m. adductor longus and magnus tend to be preserved. 4. In the leg, although the m. tibialis anterior and m. triceps surae tend to be affected, the m. peroneus longus, brevis, and m. tibialis posterior tend to be preserved. 5. Compensatory hypertrophy is often observed in the m. rectus femoris, m. adductor longus, m. adductor magnus, m. peroneus longus, and m. peroneus brevis, accompanied by the involvement of their agonist muscles. (author)

Best practice guidelines and recommendations on the molecular diagnosis of myotonic dystrophy types 1 and 2

NARCIS (Netherlands)

Kamsteeg, E.J.; Kress, W.; Catalli, C.; Hertz, J.M.; Witsch-Baumgartner, M.; Buckley, M.F.; Engelen, B.G.M. van; Schwartz, M.; Scheffer, H.

2012-01-01

Myotonic dystrophy is an autosomal dominant, multisystem disorder that is characterized by myotonic myopathy. The symptoms and severity of myotonic dystrophy type l (DM1) ranges from severe and congenital forms, which frequently result in death because of respiratory deficiency, through to

Faecal incontinence in myotonic dystrophy

OpenAIRE

Abercrombie, J; Rogers, J; Swash, M

1998-01-01

Two siblings with myotonic dystrophy presented for treatment of faecal incontinence. The pathophysiology of this functional disorder is described with the results of anorectal manometry, EMG, and biopsy of smooth and striated muscle of the anorectal sphincters. Both medical and surgical management of the incontinence was unsatisfactory in the long term. Involvement of gastrointestinal musculature is a characteristic feature the disease.



Two Cases of Endometrial Cancer in Twin Sisters with Myotonic Dystrophy

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Ezra Y. Koh

2016-01-01

Full Text Available We describe two cases of endometrial cancer (EC occurring in nulligravid twin sisters with myotonic dystrophy. Both tested negative for Lynch syndrome and both were treated with laparoscopic hysterectomy with bilateral salpingooophorectomy and adjuvant radiotherapy. Although EC tends to run in families, the diagnosis in itself is not considered sufficient cause for screening or prophylactic measures in close relatives. However, the presence of additional risk factors, such as nulligravidity and myotonic dystrophy in the underlying cases, may call for extra vigilance in first-degree family members.

Muscle pathology in myotonic dystrophy: light and electron microscopic investigation in eighteen patients.

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Nadaj-Pakleza, A; Lusakowska, A; Sułek-Piątkowska, A; Krysa, W; Rajkiewicz, M; Kwieciński, H; Kamińska, A

2011-05-01

Myotonic dystrophy (DM) is the most common muscular dystrophy in adults. Two known genetic subtypes include DM1 (myotonic dystrophy type 1) and DM2 (myotonic dystrophy type 2). Genetic testing is considered as the only reliable diagnostic criterion in myotonic dystrophies. Relatively little is known about DM1 and DM2 myopathology. Thus, the aim of our study was to characterise light and electron microscopic features of DM1 and DM2 in patients with genetically proven types of the disease. We studied 3 DM1 cases and 15 DM2 cases from which muscle biopsies were taken for diagnostic purposes during the period from 1973 to 2006, before genetic testing became available at our hospital. The DM1 group included 3 males (age at biopsy 15-19). The DM2 group included 15 patients (5 men and 10 women, age at biopsy 26-60). The preferential type 1 fibre atrophy was seen in all three DM1 cases in light microscopy, and substantial central nucleation was present in two biopsies. Electron microscopy revealed central nuclei in all three examined muscle biopsies. No other structural or degenerative changes were detected, probably due to the young age of our patients. Central nucleation, prevalence of type 2 muscle fibres, and the presence of pyknotic nuclear clumps were observed in DM2 patients in light microscopy. Among the ultrastructural abnormalities observed in our DM2 group, the presence of internal nuclei, severely atrophied muscle fibres, and lipofuscin accumulation were consistent findings. In addition, a variety of ultrastructural abnormalities were identified by us in DM2. It appears that no single ultrastructural abnormality is characteristic for the DM2 muscle pathology. It seems, however, that certain constellations of morphological changes might be indicative of certain types of myotonic dystrophy.

Vascular adrenergic receptor responses in skeletal muscle in myotonic dystrophy

International Nuclear Information System (INIS)

Mechler, F.; Mastaglia, F.L.

1981-01-01

The pharmacological responses of vascular adrenergic receptors to intravenously administered epinephrine, phentolamine, and propranolol were assessed by measuring muscle blood flow (MBF) changes in the tibialis anterior muscle using the xenon 133 clearance technique and were compared in 8 normal subjects and 11 patients with myotonic dystrophy. In cases with advanced involvement of the muscle, the resting MBF was reduced and was not significantly altered by epinephrine before or after alpha- or beta-receptor blockade. In patients in whom the tibialis anterior muscle was normal or only minimally affected clinically, a paradoxical reduction in the epinephrine-induced increase in MBF was found after alpha blockade by phentolamine, and the epinephrine-induced MBF increase was not completely blocked by propranolol as in the normal subjects. These findings point to functional alteration in the properties of vascular adrenergic receptors in muscle in myotonic dystrophy. While this may be another manifestation of a widespread cell membrane defect in the disease, the possibility that the changes are secondary to the myotonic state cannot be excluded

Psychiatric disorders appear equally in patients with myotonic dystrophy, facioscapulohumeral dystrophy, and hereditary motor and sensory neuropathy type I.

NARCIS (Netherlands)

Kalkman, J.S.; Schillings, M.L.; Zwarts, M.J.; Engelen, B.G.M. van; Bleijenberg, G.

2007-01-01

OBJECTIVES: To study the presence of psychiatric comorbidity assessed by the use of a structured clinical interview and self-reported questionnaires in a large sample of patients with adult-onset myotonic dystrophy (DM), facioscapulohumeral muscular dystrophy (FSHD), and hereditary motor and sensory

Disfagia orofaríngea na distrofia miotônica: avaliação fonoaudiológica e análise nasofibrolaringoscópica Oropharyngeal dysphagia in the myotonic dystrophy: phonoaudiological evaluation and nasofibrolaryngoscopical analysis

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Ana Lúcia de Magalhães Leal Chiappetta

2001-06-01

Full Text Available Apresentamos vinte pacientes com distrofia miotônica de Steinert, avaliados entre 1995 e 1999, pela análise fonoaudiológica e nasofibrolaringoscópica, com o objetivo de analisar e classificar as alterações da deglutição orofaríngea e funções do sistema estomatognático e considerar os fatores preditivos. A idade dos pacientes variou de 12 a 53 anos; 13 eram do sexo masculino e 7 do feminino. Os principais achados foram: (1 há relação estatisticamente significante entre avaliação fonoaudiológica e nasofibrolaringoscópica; (2 foram observadas alterações do sistema estomatognático, em 100% dos casos; (3 foram registradas alterações de deglutição em 95% dos pacientes, à avaliação fonoaudiológica, e em 70%, à nasofibrolaringoscopia; (4 os pacientes têm maior dificuldade para deglutir alimentos consistentes; (5 os músculos estomatognáticos muito alterados, desordem da fase faringeal, tosse após deglutição, antecedentes de pneumonia e queixas de mastigação/ deglutição apresentaram correlação estatisticamente significante com maior gravidade da doença. Foram avaliadas, estática e funcionalmente, estruturas envolvidas na dinâmica da deglutição. Esta avaliação deve constar da rotina do atendimento aos pacientes com distrofia miotônica de Steinert.We herein present twenty myotonic dystrophy of Steinert patients with the main objective to evaluate and classify the oropharyngeal swallowing by the phonoaudiological clinical and nasofibrolaryngoscopical analysis. The age of the patients varied from 12 to 53 years, being 13 male and 7 female. The mean data: (1 statistically significant relation between the phonoaudiological clinical evaluation and nasofibrolaryngoscopical one; (2 stomatognatical system disorders present in 100%; (3 swallowing disorders present in 95%, when clinically evaluated, and in 70% when evaluated by the nasofibrolaryngoscopy; (4 higher difficulty to swallow consistent feed; (5

Sleep disturbances in myotonic dystrophy type 2.

Science.gov (United States)

Shepard, Paul; Lam, Erek M; St Louis, Erik K; Dominik, Jacob

2012-01-01

Sleep disorders in myotonic dystrophy type 1 (DM1) are common and include sleep-disordered breathing, hypersomnia, and fatigue. Little is known regarding the occurrence of sleep disturbance in myotonic dystrophy type 2 (DM2). We hypothesized that DM2 patients may frequently harbor sleep disorders. We reviewed medical records of all genetically confirmed cases of DM2 seen at our sleep center between 1997 and 2010 for demographic, laboratory, overnight oximetry, and polysomnography (PSG) data. Eight patients (5 women, 3 men) with DM2 were identified. Excessive daytime sleepiness was seen in 6 patients (75%), insomnia in 5 (62.5%), and excessive fatigue in 4 (50%). Obstructive sleep apnea was diagnosed in 3 of 5 patients (60%) studied with PSG. Respiratory muscle weakness was present in all 6 patients (100%) who received pulmonary function testing. Four of 8 (50%) met criteria for diagnosis of restless legs syndrome. The clinical spectrum of DM2 may include a wide range of sleep disturbances. Although respiratory muscle weakness was frequent, sustained sleep-related hypoxia suggestive of hypoventilation was not seen in our patients. Further prospective studies are needed to examine the frequency and scope of sleep disturbances in DM2. Copyright © 2012 S. Karger AG, Basel.

Prevalence and correlates of apathy in myotonic dystrophy type 1

OpenAIRE

Gallais, Benjamin; Montreuil, Mich?le; Gargiulo, Marcela; Eymard, Bruno; Gagnon, Cynthia; Laberge, Luc

2015-01-01

Background Apathy in DM1 has long been acknowledged in clinical practice. However, a major drawback is that the concept has been only sparsely explored in previous specific studies. This study aimed to determine the prevalence of apathy in myotonic dystrophy (DM1), to compare it with facioscapulohumeral dystrophy (FSHD) patients and normal healthy controls, and explore its relationship to psychopathological features and cognitive function. Methods Levels of apathy in 38 DM1 patients with adul...

EEG observations in dystrophia myotonica (Curschmann-Steinert)

NARCIS (Netherlands)

Beijersbergen, R.H.S.M.; Kemp, A.; Storm van Leeuwen, W.

An investigation has been carried out in a group of 84 (+2) patients suffering from myotonic dystrophia (Curschmann-Steinert). Manual measurements show that in these patients: (1) the alpha rhythms have low frequencies, related to the age of the patient and to the duration and severity of the

1H and 31P nuclear magnetic resonance spectroscopy of erythrocyte extracts in myotonic muscular dystrophy

International Nuclear Information System (INIS)

Gadoth, N.; Grinblat, J.; Tel Aviv Univ.; Shvo, H.; Navon, G.

1984-01-01

Extracts freshly prepared from erythrocytes of patients with myotonic muscular dystrophy, their unaffected siblings, and normal control subjects were examined with both 1 H and 31 P nuclear magnetic resonance spectroscopy. A moderate variability was found in the relative amounts of various nonphosphorylated compounds among patients and control subjects; however, no significant differences were found between the groups. As for the phosphorylated compounds, the sum of ADP+ATP was found significantly elevated in the myotonic muscular dystrophy patients

[Perioperative treatment of a patient with myotonic muscular dystrophy (Curschmann-Steinert disease)].

Science.gov (United States)

Thölke, M H; Tolksdorf, W; Mitrenga, I

1991-04-01

The perioperative period is hazardous for patients with neuromuscular disorder. In case of dystrophia myotonica the anaesthesist must avoid all stimuli that may cause a myotonic crisis. If neuromuscular blockade is required, the moderately long-acting vecuronium bromide seems to be the drug of first choice. Blockade and recovery should be monitored. Postoperative pulmonary complications can be minimised by using regional anaesthetic techniques including epidural anaesthesia with local anaesthetics and/or opioids.

A neonate with congenital myotonic dystrophy

International Nuclear Information System (INIS)

Itani, Yasufumi; Anbo, Kazutoshi; Kashiwagi, Sigeru; Yokoya, Susumu; Kato, Kazuo

1984-01-01

A boy's neonate with congenital myotonic dystrophy who had difficulty in breathing immediately after birth was reported. A long-term management for artificial breathing was required because of a marked decrease of muscular tone, equinus and the difficulty in sucking milk. Myogenic pattern was seen on EMG and atrophied type I fibers and increased number of type 2 C fibers suggesting the prolongation of differentiation of muscle fibers were seen by muscle biopsy. Cranial CT revealed a marked atrophy of the cerebral cortex and low density area in the white matter, although the latter disappeared 4 months later. (Namekawa, K.)

Cell membrane integrity in myotonic dystrophy type 1: implications for therapy

NARCIS (Netherlands)

Gonzalez, A.M.M.; Kranzen, J.; Croes, H.J.E.; Bijl, S.; Broek, W.J.A.A. van den; Kessel, I.D.G. van; Engelen, B.G.M. van; Deutekom, J.C. van; Wieringa, B.; Mulders, S.A.; Wansink, D.G.

2015-01-01

Myotonic Dystrophy type 1 (DM1) is a multisystemic disease caused by toxic RNA from a DMPK gene carrying an expanded (CTG*CAG)n repeat. Promising strategies for treatment of DM1 patients are currently being tested. These include antisense oligonucleotides and drugs for elimination of expanded RNA or

Involvement of the central nervous system in myotonic dystrophy

International Nuclear Information System (INIS)

Fukui, Ritsuko; Tobimatsu, Shozo; Kuroiwa, Yoshigoro; Iwashita, Hiroshi; Kato, Motohiro.

1985-01-01

In order to evaluate the central nervous system involvement in myotonic dystrophy, intelligence quotient (IQ), brain CT scan, EEG and pattern-reversal visual evoked potential (VEP) were analyzed in 10 patients with myotonic dystrophy. Impaired intelligence was observed in 9 out of 10 patients, abnormal brain CT in 7, and EEG abnormality in 7. The brain CT showed a diffuse cortical atrophy, a dilatation of the ventricles, and a periventricular lucency, mainly around the anterior horn of the lateral ventricle. The EEG findings showed a tendency toward generalized slowing of the background activity. These abnormal findings were well related to the clinical severity of MD, indicating that there is a diffuse cerebral involvement in the majority of the MD patients. VEP showed a prolonged P100 latency in 5 out of 10 patints, or 7 out of 19 eyes examined. These prolonged latency of the P100 component was considered to be due to dysfunctions of the visual pathway in the cerebral hemisphere, rather than due to cataracts and retinal dysfunctions because it was observed only in moderate and severe cases. These severe and moderate cases showed abnormalities in all four examinations. It was concluded that combination of different parameters might be useful to evaluate the central nervous system involvement in patients with MD. (author)

Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds

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Arandel, Ludovic; Polay Espinoza, Micaela; Matloka, Magdalena; Bazinet, Audrey; De Dea Diniz, Damily; Naouar, Naïra; Rau, Frédérique; Jollet, Arnaud; Edom-Vovard, Frédérique; Mamchaoui, Kamel; Tarnopolsky, Mark; Puymirat, Jack; Battail, Christophe; Boland, Anne; Deleuze, Jean-Francois; Mouly, Vincent; Klein, Arnaud F.

2017-01-01

ABSTRACT Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared with control and DM2 cells. Alternative splicing defects were observed in differentiated DM1 muscle cell lines, but not in DM2 lines. Splicing alterations did not result from differentiation delay because similar changes were found in immortalized DM1 transdifferentiated fibroblasts in which myogenic differentiation has been forced by overexpression of MYOD1. As a proof-of-concept, we show that antisense approaches alleviate disease-associated defects, and an RNA-seq analysis confirmed that the vast majority of mis-spliced events in immortalized DM1 muscle cells were affected by antisense treatment, with half of them significantly rescued in treated DM1 cells. Immortalized DM1 muscle cell lines displaying characteristic disease-associated molecular features such as nuclear RNA aggregates and splicing defects can be used as robust readouts for the screening of therapeutic compounds. Therefore, immortalized DM1 and DM2 muscle cell lines represent new models and tools to investigate molecular pathophysiological mechanisms and evaluate the in vitro effects of compounds on RNA toxicity associated with myotonic dystrophy mutations. PMID:28188264

Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds

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Ludovic Arandel

2017-04-01

Full Text Available Myotonic dystrophy type 1 (DM1 and type 2 (DM2 are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared with control and DM2 cells. Alternative splicing defects were observed in differentiated DM1 muscle cell lines, but not in DM2 lines. Splicing alterations did not result from differentiation delay because similar changes were found in immortalized DM1 transdifferentiated fibroblasts in which myogenic differentiation has been forced by overexpression of MYOD1. As a proof-of-concept, we show that antisense approaches alleviate disease-associated defects, and an RNA-seq analysis confirmed that the vast majority of mis-spliced events in immortalized DM1 muscle cells were affected by antisense treatment, with half of them significantly rescued in treated DM1 cells. Immortalized DM1 muscle cell lines displaying characteristic disease-associated molecular features such as nuclear RNA aggregates and splicing defects can be used as robust readouts for the screening of therapeutic compounds. Therefore, immortalized DM1 and DM2 muscle cell lines represent new models and tools to investigate molecular pathophysiological mechanisms and evaluate the in vitro effects of compounds on RNA toxicity associated with myotonic dystrophy mutations.

Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds.

Science.gov (United States)

Arandel, Ludovic; Polay Espinoza, Micaela; Matloka, Magdalena; Bazinet, Audrey; De Dea Diniz, Damily; Naouar, Naïra; Rau, Frédérique; Jollet, Arnaud; Edom-Vovard, Frédérique; Mamchaoui, Kamel; Tarnopolsky, Mark; Puymirat, Jack; Battail, Christophe; Boland, Anne; Deleuze, Jean-Francois; Mouly, Vincent; Klein, Arnaud F; Furling, Denis

2017-04-01

Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded repeats, a hallmark of myotonic dystrophy. Selected clones of DM1 and DM2 immortalized myoblasts behave as parental primary myoblasts with a reduced fusion capacity of immortalized DM1 myoblasts when compared with control and DM2 cells. Alternative splicing defects were observed in differentiated DM1 muscle cell lines, but not in DM2 lines. Splicing alterations did not result from differentiation delay because similar changes were found in immortalized DM1 transdifferentiated fibroblasts in which myogenic differentiation has been forced by overexpression of MYOD1. As a proof-of-concept, we show that antisense approaches alleviate disease-associated defects, and an RNA-seq analysis confirmed that the vast majority of mis-spliced events in immortalized DM1 muscle cells were affected by antisense treatment, with half of them significantly rescued in treated DM1 cells. Immortalized DM1 muscle cell lines displaying characteristic disease-associated molecular features such as nuclear RNA aggregates and splicing defects can be used as robust readouts for the screening of therapeutic compounds. Therefore, immortalized DM1 and DM2 muscle cell lines represent new models and tools to investigate molecular pathophysiological mechanisms and evaluate the in vitro effects of compounds on RNA toxicity associated with myotonic dystrophy mutations. © 2017. Published by The Company of Biologists Ltd.

Science.gov (United States)

NIGRO, GERARDO; PAPA, ANDREA ANTONIO; POLITANO, LUISA

2012-01-01

Myotonic dystrophy (Dystrophia Myotonica, DM) is the most frequently inherited neuromuscular disease of adult life. It is a multisystemic disease with major cardiac involvement. Core features of myotonic dystrophy are myotonia, muscle weakness, cataract, respiratory failure and cardiac conduction abnormalities. Classical DM, first described by Steinert and called Steinert's disease or DM1 (Dystrophia Myotonica type 1) has been identified as an autosomal dominant disorder associated with the presence of an abnormal expansion of a CTG trinucleotide repeat in the 3' untranslated region of DMPK gene on chromosome 19. This review will mainly focus on the various aspects of cardiac involvement in DM1 patients and the current role of cardiac pacing in their treatment. PMID:23097601

French translation and cross-cultural adaptation of The Myotonic Dystrophy Health Index.

Science.gov (United States)

Gagnon, Cynthia; Tremblay, Marjolaine; CôTé, Isabelle; Heatwole, Chad

2018-04-01

Validation studies of disease-specific instruments for myotonic dystrophy type-1 (DM1) are required prior to their global use in clinical trials involving different cultures and countries. Here we translate and culturally adapt the Myotonic Dystrophy Health Index (MDHI), a disease-specific patient-reported outcome (PRO) measure, for a French DM1 population. Using the International Society for Pharmacoeconomics and Outcomes Research Task Force method for translation and adaptation of PRO questionnaires, we created a French translation of the MDHI. We subsequently tested this instrument in a cohort of French-speaking patients with DM1. The MDHI was forward and back translated and modified by consensus to create the most compatible translation. Cognitive interviews were conducted with 5 patients with DM1 to ensure the usability and understanding of the translation. The French version of the MDHI is an optimal translation of the original instrument that is acceptable to native patients and ready for clinical trial use. Muscle Nerve 57: 686-689, 2018. © 2017 Wiley Periodicals, Inc.

Myotonic Dystrophy Type 1 Management and Therapeutics.

Science.gov (United States)

Smith, Cheryl A; Gutmann, Laurie

2016-12-01

Myotonic dystrophy (DM1) is the most common form of adult muscular dystrophy. It is a multisystem disorder with a complex pathophysiology. Although inheritance is autosomal dominant, disease variability is attributed to anticipation, a maternal expansion bias, variable penetrance, somatic mosaicism, and a multitude of aberrant pre-mRNA splicing events. Patient presentations range from asymptomatic or mild late onset adult to severe congenital forms. Multiple organ systems may be affected. Patients may experience early cataracts, myotonia, muscle weakness/atrophy, fatigue, excessive daytime sleepiness, central/obstructive apnea, respiratory failure, cardiac arrhythmia, insulin resistance, dysphagia, GI dysmotility, cognitive impairment, Cluster C personality traits, and/or mood disorders. At present, there is no curative or disease-modifying treatment, although clinical treatment trials have become more promising. Management focuses on genetic counseling, preserving function and independence, preventing cardiopulmonary complications, and symptomatic treatment (e.g., pain, myotonia, hypersomnolence, etc.). Currently, there is an increasing international consensus on monitoring and treatment options for these patients which necessitates a multidisciplinary team to provide comprehensive, coordinated clinical care.

Peripheral neuropathy in patients with myotonic dystrophy type 2.

Science.gov (United States)

Leonardis, L

2017-05-01

Myotonic dystrophy type 2 (dystrophia myotonica type 2-DM2) is an autosomal dominant multi-organ disorder. The involvement of the peripheral nervous system was found in 25%-45% of patients with myotonic dystrophy type 1, although limited data are available concerning polyneuropathy in patients with DM2, which was the aim of this study with a thorough presentation of the cases with peripheral neuropathy. Patients with genetically confirmed DM2 underwent motor nerve conduction studies of the median, ulnar, tibial and fibular nerves and sensory nerve conduction studies of the median (second finger), ulnar (fifth finger), radial (forearm) and sural nerves. Seventeen adult patients with DM2 participated in the study. Fifty-three percent (9/17) of our patients had abnormality of one or more attributes (latency, amplitude or conduction velocity) in two or more separate nerves. Four types of neuropathies were found: (i) predominantly axonal motor and sensory polyneuropathy, (ii) motor polyneuropathy, (iii) predominantly demyelinating motor and sensory polyneuropathy and (iv) mutilating polyneuropathy with ulcers. The most common forms are axonal motor and sensory polyneuropathy (29%) and motor neuropathy (18% of all examined patients). No correlations were found between the presence of neuropathy and age, CCTG repeats, blood glucose or HbA1C. Peripheral neuropathy is common in patients with DM2 and presents one of the multisystemic manifestations of DM2. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Living with myotonic dystrophy; what can be learned from couples? A qualitative study

NARCIS (Netherlands)

Cup, E.H.C.; Kinebanian, A.; Satink, T.J.; Pieterse, A.J.; Hendricks, H.T.; Oostendorp, R.A.B.; Wilt, G.J. van der; Engelen, B.G.M. van

2011-01-01

BACKGROUND: Myotonic dystrophy type 1 (MD1) is one of the most prevalent neuromuscular diseases, yet very little is known about how MD1 affects the lives of couples and how they themselves manage individually and together. To better match health care to their problems, concerns and needs, it is

Muscle phenotype in patients with myotonic dystrophy type 1

DEFF Research Database (Denmark)

Andersen, Anne Grete Kielgast; Orngreen, Mette C; Preisler, Nicolai Rasmus

2012-01-01

Introduction: The pathogenesis of muscle involvement in patients with myotonic dystrophy type 1 (DM1) is not well understood. In this study, we characterized the muscle phenotype in patients with confirmed DM1. Methods: In 38 patients, muscle strength was tested by hand-held dynamometry. Myotonia...... was evaluated by a handgrip test and by analyzing the decrement of the compound muscle action potential. Muscle biopsies were assessed for morphological changes and Na(+) -K(+) pump content. Results: Muscle strength correlated with a decline in Na(+) -K(+) pump content (r = 0.60, P

Reliability and feasibility of the six minute walk test in subjects with myotonic dystrophy.

Science.gov (United States)

Kierkegaard, Marie; Tollbäck, Anna

2007-12-01

The objective was to describe test-retest reliability and feasibility of the six minute walk test in adult subjects with myotonic dystrophy type 1. Twelve subjects (28-68 years, mean 44) performed three six minute walk tests on two occasions, one week apart. Relative reliability was high (ICC(2.1)=0.99) and absolute reliability values were low (standard error of measurement 12 m, repeatability 33 m). Feasibility was investigated in a sample of 64 subjects (19-70 years, mean 43). Fifty-two subjects were able to perform two tests on the same day. Subjects with severe proximal weakness had difficulties performing repeated tests. A practice trial followed by a second test on the same day can be recommended for most subjects, and the best test should be used for evaluations. In conclusion, even though the study sample was small, the present study indicates that the six minute walk test is reliable and feasible in subjects with myotonic dystrophy type 1.

Perceived functioning and disability in adults with myotonic dystrophy type 1: a survey according to the International Classification Of Functioning, Disability and Health.

Science.gov (United States)

Kierkegaard, Marie; Harms-Ringdahl, Karin; Widén Holmqvist, Lotta; Tollbäck, Anna

2009-06-01

The purpose of this study was to describe and analyse self-rated perceived functioning, disability and environmental facilitators/barriers with regard to disease severity, using the International Classification of Functioning, Disability and Health (ICF) checklist, in adults with myotonic dystrophy type 1. Cross-sectional design. Forty-one women and 29 men with myotonic dystrophy type 1. A modified ICF checklist was used for self-rating of perceived problems in 29 body-function categories, difficulties in 52 activity and participation categories, and facilitators/barriers in 23 environmental-factor categories according to the verbal anchors of the ICF qualifiers. Disease severity classification was based on the muscular impairment rating scale. Of the persons with myotonic dystrophy type 1, 80% perceived problems of excessive daytime sleepiness, 76% of muscle power, and 66% of energy and drive functions, while over 59% perceived difficulties in physically demanding mobility activities. Disabilities in mobility, self-care and domestic life were more frequently reported by persons with severe disease. Support from the immediate family, medicines and social security services were perceived as facilitators for 50-60% of the participants. Disabilities and important environmental facilitators in adults with myotonic dystrophy type 1 were identified, and this clinically-relevant information can be used for developing health services for people with this condition.

Myotonic dystrophy type 1 with diabetes mellitus, mixed hypogonadism and adrenal insufficiency

Directory of Open Access Journals (Sweden)

Ken Takeshima

2018-01-01

Full Text Available Myotonic dystrophy type 1 (DM1 is an autosomal dominant multisystem disease affecting muscles, the eyes and the endocrine organs. Diabetes mellitus and primary hypogonadism are endocrine manifestations typically seen in patients with DM1. Abnormalities of hypothalamic–pituitary–adrenal (HPA axis have also been reported in some DM1 patients. We present a case of DM1 with a rare combination of multiple endocrinopathies; diabetes mellitus, a combined form of primary and secondary hypogonadism, and dysfunction of the HPA axis. In the present case, diabetes mellitus was characterized by severe insulin resistance with hyperinsulinemia. Glycemic control improved after modification of insulin sensitizers, such as metformin and pioglitazone. Hypogonadism was treated with testosterone replacement therapy. Notably, body composition analysis revealed increase in muscle mass and decrease in fat mass in our patient. This implies that manifestations of hypogonadism could be hidden by symptoms of myotonic dystrophy. Our patient had no symptoms associated with adrenal deficiency, so adrenal dysfunction was carefully followed up without hydrocortisone replacement therapy. In this report, we highlight the necessity for evaluation and treatment of multiple endocrinopathies in patients with DM1.

Design and analysis of effects of triplet repeat oligonucleotides in cell models for myotonic dystrophy

NARCIS (Netherlands)

Gonzalez-Barriga, A.; Mulders, S.A.M.; Giessen, J. van der; Hooijer, J.D.; Bijl, S.; Kessel, I.D.G. van; Beers, J. van; Deutekom, J.C. van; Fransen, J.A.M.; Wieringa, B.; Wansink, D.G.

2013-01-01

Myotonic dystrophy type 1 (DM1) is caused by DM protein kinase (DMPK) transcripts containing an expanded (CUG)n repeat. Antisense oligonucleotide (AON)-mediated suppression of these mutant RNAs is considered a promising therapeutic strategy for this severe disorder. Earlier, we identified a

Can long-term thiamine treatment improve the clinical outcomes of myotonic dystrophy type 1?

Directory of Open Access Journals (Sweden)

Antonio Costantini

2016-01-01

Full Text Available Myotonic dystrophy type 1, also known as Steinert′s disease, is an autosomal dominant disorder with multisystemic clinical features affecting the skeletal and cardiac muscles, the eyes, and the endocrine system. Thiamine (vitamin B1 is a cofactor of fundamental enzymes involved in the energetic cell metabolism; recent studies described its role in oxidative stress, protein processing, peroxisomal function, and gene expression. Thiamine deficiency is critical mainly in the central and peripheral nervous system, as well as in the muscular cells. Our aim was to investigate the potential therapeutical effects of long-term treatment with thiamine in myotonic dystrophy type 1 in an observational open-label pilot study. We described two patients with myotonic dystrophy type 1 treated with intramuscular thiamine 100 mg twice a week for 12 or 11 months. We evaluated the patients using the grading of muscle strength according to Medical Research Council (MRC, the Muscular Impairment Rating Scale (MIRS, and the Modified Barthel index. High-dose thiamine treatment was well tolerated and effective in improving the motor symptomatology, particularly the muscle strength evaluated with the MRC scale, and the patients′ activities of daily living using the Modified Barthel Index. At the end of treatment, the MRC score was 5 in the proximal muscles and 2-4 in the distal muscles (the MRC score before the treatment was 3-4 and 1-3, respectively. The MIRS grade improved by 25% compared to baseline for both patients. In patient #1, the Modified Barthel Index improved by 44%, and in patient #2 by 29%. These findings suggest that clinical outcomes are improved by long-term thiamine treatment.

Molecular and preclinical aspects of antisense oligonucleotide treatment for myotonic dystrophy type 1

NARCIS (Netherlands)

Gonzalez Barriga, A.M.M.

2017-01-01

Myotonic Dystrophy type 1 (DM1) is a genetic disorder caused by an expansion of a (CTG)n repeat in the DMPK gene, which is carried by all individuals, but normally contains less than 37 triplets. Only when this threshold is exceeded the person carrying it will develop DM1, with an age of onset and

Immortalized human myotonic dystrophy muscle cell lines to assess therapeutic compounds

OpenAIRE

Arandel, Ludovic; Polay Espinoza, Micaela; Matloka, Magdalena; Bazinet, Audrey; De Dea Diniz, Damily; Naouar, Na?ra; Rau, Fr?d?rique; Jollet, Arnaud; Edom-Vovard, Fr?d?rique; Mamchaoui, Kamel; Tarnopolsky, Mark; Puymirat, Jack; Battail, Christophe; Boland, Anne; Deleuze, Jean-Francois

2017-01-01

International audience; Myotonic dystrophy type 1 (DM1) and type 2 (DM2) are autosomal dominant neuromuscular diseases caused by microsatellite expansions and belong to the family of RNA-dominant disorders. Availability of cellular models in which the DM mutation is expressed within its natural context is essential to facilitate efforts to identify new therapeutic compounds. Here, we generated immortalized DM1 and DM2 human muscle cell lines that display nuclear RNA aggregates of expanded rep...

Risk of cancer in relatives of patients with myotonic dystrophy

DEFF Research Database (Denmark)

Lund, M; Diaz, L J; Gørtz, S

2014-01-01

BACKGROUND AND PURPOSE: Myotonic dystrophies (DM) are autosomal dominantly inherited neuromuscular disorders caused by unstable nucleotide repeat expansions. DM and cancer have been associated, but the pathogenesis behind the association remains unclear. It could relate to derived effects of the DM...... genotype in which case non-DM relatives of DM patients would not be expected to be at increased risk of cancer. To elucidate this, a population-based cohort study investigating risk of cancer in relatives of DM patients was conducted. METHODS: DM was identified using the National Danish Patient Registry...

Triplet repeat sequences in human DNA can be detected by hybridization to a synthetic (5'-CGG-3')17 oligodeoxyribonucleotide

DEFF Research Database (Denmark)

Behn-Krappa, A; Mollenhauer, J; Doerfler, W

1993-01-01

The seemingly autonomous amplification of naturally occurring triplet repeat sequences in the human genome has been implicated in the causation of human genetic disease, such as the fragile X (Martin-Bell) syndrome, myotonic dystrophy (Curshmann-Steinert), spinal and bulbar muscular atrophy...

Benign and malignant tumors in the UK myotonic dystrophy patient registry.

Science.gov (United States)

Alsaggaf, Rotana; Wang, Youjin; Marini-Bettolo, Chiara; Wood, Libby; Nikolenko, Nikoletta; Lochmüller, Hanns; Greene, Mark H; Gadalla, Shahinaz M

2018-02-01

In light of recent evidence indicating that cancer is part of the myotonic dystrophy (DM) phenotype, we assessed the prevalence of benign and malignant tumors among 220 patients enrolled in the UK Myotonic Dystrophy Patient Registry and evaluated factors associated with their development. A survey was distributed to collect tumor history and lifestyle information. We used multinomial logistic regression for the analysis. Thirty-nine benign (30 patients), and 16 malignant (15 patients) tumors were reported. Increasing age (odds ratio [OR] = 1.13, 95% confidence interval [CI] = 1.05-1.21, P = 0.001) and earlier age at DM diagnosis (OR = 1.06, 95% CI = 1.00-1.13, P = 0.04) were associated with benign and malignant tumors (OR = 1.20, 95% CI = 1.10-1.30, P < 0.001 and OR = 1.08, 95% CI = 1.01-1.15, P = 0.02, respectively). Female gender was associated with benign tumors only (OR = 6.43, 95% CI = 1.79-23.04, P = 0.004). No associations were observed between tumors and smoking (P = 0.24), alcohol consumption (P = 0.50), or body mass index (P = 0.21). Our results confirm previous findings suggesting a limited role for common lifestyle factors and a potential genetic contribution in DM tumor predisposition. Muscle Nerve 57: 316-320, 2018. © 2017 Wiley Periodicals, Inc.

Best practice guidelines and recommendations on the molecular diagnosis of myotonic dystrophy types 1 and 2

DEFF Research Database (Denmark)

Kamsteeg, Erik-Jan; Kress, Wolfram; Catalli, Claudio

2012-01-01

-onset baldness and cataract. In adult patients, cardiac conduction abnormalities may occur and cause a shorter life span. In subsequent generations, the symptoms in DM1 may present at an earlier age and have a more severe course (anticipation). In myotonic dystrophy type 2 (DM2), no anticipation is described...

Genotype–Phenotype Correlations in Iranian Myotonic Dystrophy Type I Patients

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Kimia Kahrizi

2010-04-01

Full Text Available Objectives: Myotonic Dystrophy type I (DM1 is a dominantly inherited disorder with a multisystemic pattern affecting skeletal muscle, heart, eye, endocrine and central nervous system. DM1 is associated with the expansion and instability of CTG repeat in the 3' untranslated region of the myotonic dystrophy protein kinase (DMPK gene located on chromosome 19q13.3. The aim of this study was to determine clinical and genetic characteristic of DM1 in Iranian patients. Genotype-phenotype correlation was also assessed in a small group of studied patients. Methods: Twenty six DM1 patients belonging to seventeen families were analyzed. Clinical assessment was based on the muscular disability rating scale (MDRS and a sum of symptoms score (SSS. Molecular analysis (PCR and Southern blot was used to clarify uncertain clinical diagnosis and in order to confirm clinical findings. Results: There was an inverse and significant correlation between age of onset  and expanded allele  length (P=0.026, tau-b=-0.360 based on Kendall's tau-b correlation coefficient, while there was no significant correlation between age of onset and severity of the clinical symptoms (P<0.05. Also no significant correlation was observed between the two severity scales of the disease (MDRS and SSS and expanded allele length (P<0.05. Expanded allele length was correlated with hypogonadism (P=0.007 and cognitive impairment (P=0.034. Discussion: There was no correlation between cataract and endocrine dysfunction with the expansion size in DM1 patients. Generally it seems there is discordant correlation between clinical symptoms and expanded allele length.

A low absolute number of expanded transcripts is involved in myotonic dystrophy type 1 manifestation in muscle

NARCIS (Netherlands)

Gudde, A.E.; Gonzalez-Barriga, A.; Broek, W.J. van den; Wieringa, B.; Wansink, D.G.

2016-01-01

Muscular manifestation of myotonic dystrophy type 1 (DM1), a common inheritable degenerative multisystem disorder, is mainly caused by expression of RNA from a (CTG.CAG)n-expanded DM1 locus. Here, we report on comparative profiling of expression of normal and expanded endogenous or transgenic

Musculoskeletal pain in patients with myotonic dystrophy type 2.

Science.gov (United States)

George, Annette; Schneider-Gold, Christiane; Zier, Sandra; Reiners, Karlheinz; Sommer, Claudia

2004-12-01

Myotonic dystrophy type 2/proximal myotonic myopathy (DM2/PROMM) is an autosomal dominant multisystem disorder. Musculoskeletal pain is one of its frequent symptoms but also occurs in other chronic noninflammatory muscle disorders (OMD). To characterize the phenotype of DM2/PROMM-associated musculoskeletal pain and to test whether it shows features distinct from OMD. Outpatient clinic for patients with neuromuscular disorders, university hospital. Twenty-four patients with DM2/PROMM (12 women and 12 men; median age, 57 years) and 24 age- and sex-matched patients with OMD consecutively recruited during a 3-year period were examined for musculoskeletal pain. Standardized pain assessment; McGill Pain Questionnaire; depression score; and quantification of pain thresholds to blunt pressure on limb muscles with analgometer. Unlike patients with OMD who have musculoskeletal pain, patients with DM2/PROMM distinguished a wide spectrum of coexisting pain types. The major pain type in patients with DM2/PROMM was exercise-related, temperature-modulated, and palpation-induced, whereas, cramps were rare. In 8 of the patients with DM2/PROMM and in 3 of the patients with OMD, musculoskeletal pain was the most disabling symptom. Besides many similarities, DM2/PROMM-associated musculoskeletal pain shows features distinct from OMD.

Feasibility and effects of a physical exercise programme in adults with myotonic dystrophy type 1: a randomized controlled pilot study.

Science.gov (United States)

Kierkegaard, Marie; Harms-Ringdahl, Karin; Edström, Lars; Widén Holmqvist, Lotta; Tollbäck, Anna

2011-07-01

To investigate the feasibility and effects of a physical exercise programme on functioning and health-related quality of life in adults with myotonic dystrophy type 1. A randomized controlled trial. Thirty-five adults with myotonic dystrophy type 1. After stratification for level of functioning, study participants were assigned by lot to either a training group or a control group. Training-group participants attended a 60-minute comprehensive group-training programme, Friskis&Svettis® Open Doors, twice a week for 14 weeks. The six-minute walk test was the primary outcome measure and the timed-stands test, the timed up-and-go test, the Epworth sleepiness scale and the Short Form-36 health survey were secondary outcome measures. Intention-to-treat analyses revealed no significant differences in any outcome measures, except for an increased between-group difference after intervention in the Short Form-36 mental health subscale and a decrease in the vitality subscale for the control group. The programme was well tolerated and many training-group participants perceived subjective changes for the better. No negative effects were reported. The Friskis&Svettis® Open Doors programme was feasible for adults with myotonic dystrophy type 1 who had been screened for cardiac involvement, had distal or mild-to-moderate proximal muscle impairment, and no severe cognitive impairments. No beneficial or detrimental effects were evident.

[Educational and Professional Qualifications of Adults With Myotonic Dystrophies - A Misleading Perception by the Myopathic Face?].

Science.gov (United States)

Stahl, K; Wenninger, S; Schüller, A; Montagnese, F; Schoser, B

2016-04-01

Myotonic dystrophies types 1 and 2 (DM1 / DM2) are the most frequent inherited progressive, segmental progeroid, multisystemic neuromuscular diseases in adulthood. The executive impairment is one of the key disease features. The myopathic face triggers the general perception of DM1 patients being associated with a low educational level. We used a standardized questionnaire to evaluate educational levels in adults with genetically confirmed DM1 and DM2 in comparison to data of the general population. Investigated topics included the level of education, e. g. the highest university degree aquired. Out of a total cohort of 546 DM patients, 125 DM1 and 156 DM2 patients (51 %) participated in this study. There was no statistically significant difference between the two collectives as far as high school levels are concerned. 50.4 % of DM1 and 48.3 % of DM2 patients obtained the higher education entrance qualification compared to 29.6 % of the normal German population. However, there were significant differences between the two collectives in "spelling problems" (DM1 cohort: p = 0.039), "difficulty in mental arithmetic" (p = 0.043), and classification of patients "with learning difficulties" (p = 0.012). Misled by a myopathic face, many physicians associate myotonic dystrophy with cognitive deficiency. Based on our study, the minimal deviation between DM1 and DM2 and the normal German population indicates that the multisystemic disease does not significantly influence the maximum attainable level of education in adults with DM1. In summary, physicians should be aware that the general educational levels are rather normal in patients with myotonic dystrophy type 1 and rethink their perception of DM1 patients. © Georg Thieme Verlag KG Stuttgart · New York.

Can long-term thiamine treatment improve the clinical outcomes of myotonic dystrophy type 1?

OpenAIRE

Costantini, Antonio; Trevi, Erika; Pala, Maria Immacolata; Fancellu, Roberto

2016-01-01

Myotonic dystrophy type 1, also known as Steinert′s disease, is an autosomal dominant disorder with multisystemic clinical features affecting the skeletal and cardiac muscles, the eyes, and the endocrine system. Thiamine (vitamin B1) is a cofactor of fundamental enzymes involved in the energetic cell metabolism; recent studies described its role in oxidative stress, protein processing, peroxisomal function, and gene expression. Thiamine deficiency is critical mainly in the central and periphe...

Sequestration of MBNL1 Protein by Mutant ZNF9 mRNA in Lymphocytes of Patients with Myotonic Dystrophy Type 2

Czech Academy of Sciences Publication Activity Database

Souček, O.; Voháňka, S.; Zaorálková, J.; Falková, I.; Hrabálková, R.; Falk, Martin; Lukáš, Z.

2012-01-01

Roč. 75, č. 5 (2012), s. 606-609 ISSN 1210-7859 Institutional research plan: CEZ:AV0Z50040702 Institutional support: RVO:68081707 Keywords : myotonic dystrophy * lymphocytes * MBNL1 sequestration Subject RIV: BO - Biophysics Impact factor: 0.366, year: 2012

Molecular Genetic Analysis of Fetal Tissues from a Family Affected by Myotonic Dystrophy

Czech Academy of Sciences Publication Activity Database

Lukáš, Z.; Falk, Martin; Falková, I.; Feit, J.; Fajkusová, L.; Zítková, J.; Valášková, I.

2012-01-01

Roč. 75, č. 6 (2012), s. 730-736 ISSN 1210-7859 R&D Projects: GA AV ČR(CZ) IAA500040802; GA ČR GBP302/12/G157; GA ČR(CZ) GAP302/10/1022; GA MŠk(CZ) LD12039; GA MŠk(CZ) EE2.3.30.0030 Grant - others:IBCT(XE) MP1002 Nano-IBCT Institutional research plan: CEZ:AV0Z50040702 Institutional support: RVO:68081707 Keywords : myotonic dystrophy * DMPK mutation * fetal tissue Subject RIV: BO - Biophysics Impact factor: 0.366, year: 2012

Is the epicardial left ventricular lead implantation an alternative approach to percutaneous attempt in patients with Steinert disease? A case report

Science.gov (United States)

PAPA, ANDREA ANTONIO; RAGO, ANNA; PETILLO, ROBERTA; D’AMBROSIO, PAOLA; SCUTIFERO, MARIANNA; FEO, MARISA DE; MAIELLO, CIRO; PALLADINO, ALBERTO

2017-01-01

Steinert’s disease or Myotonic Dystrophy type 1 (DM1) is an autosomal dominant multisystemic disorder characterized by myotonia, muscle and facial weakness, cataracts, cognitive, endocrine and gastrointestinal involvement, and cardiac conduction abnormalities. Although mild myocardial dysfunction may be detected in this syndrome with age, overt myocardial dysfunction with heart failure is not frequent. Cardiac resynchronization therapy is an effective treatment to improve morbidity and reduce mortality in patients with DM1 showing intra-ventricular conduction delay and/or congestive heart failure. We report the case of a patient with Steinert disease showing an early onset ventricular dysfunction due to chronic right ventricular apical pacing, in which an epicardial left ventricular lead implantation was performed following the failure of the percutaneous attempt. As no relief in symptoms of heart failure, nor an improvement of left ventricular ejection fraction and reverse remodelling was observed six months later, the patient was addressed to the heart transplantation.

Anestesia para colecistectomia videolaparoscópica em paciente portador de Doença de Steinert: relato de caso e revisão de literatura Anestesia para colecistectomía videolaparoscópica en oaciente oortador de Enfermedad de Steinert: relato de caso y revisión de la literatura Anesthesia for videolaparoscopic cholecystectomy in a patient with Steinert Disease: case report and review of the literature

Directory of Open Access Journals (Sweden)

Flora Margarida Barra Bisinotto

2010-04-01

anestesiólogo. Los pacientes presentan una mayor sensibilidad a los fármacos anestésicos y complicaciones, principalmente cardíacas y pulmonares. Además de eso, existe la posibilidad de presentar hipertermia maligna y crisis miotónica. Se ha descrito el caso de un paciente que tuvo una complicación pulmonar importante después de haber sido sometido a la anestesia general. RELATO DEL CASO: Paciente de 39 años, portador de DM1, sometido a la anestesia general para colecistectomía videolaparoscópica. La anestesia fue venosa total con propofol y remifentanil y rocuronio. El procedimiento quirúrgico de 90 minutos no presentó intercurrencias, pero después de la extubación, el paciente presentó insuficiencia respiratoria y crisis miotónica, que hizo la intubación traqueal imposible. Se utilizó la máscara laríngea, que posibilitó la oxigenación adecuada, y la ventilación mecánica se mantuvo hasta la recuperación total de la actividad respiratoria. Evolucionó sin otras complicaciones. CONCLUSIONES: La DM1 es una enfermedad que presenta varias peculiaridades para el anestesiólogo. El conocimiento minucioso de su involucración sistémica, asociado a la acción diferenciada de los fármacos anestésicos en esos pacientes, proporcionará un acto anestésico-quirúrgico más seguro.BACKGROUND AND OBJECTIVES: Myotonic dystrophies are autosomal dominant neuromuscular diseases. Among them, myotonic dystrophy type 1 (MD1, or Steinert disease, is the most common in adults, and besides muscular involvement it also has important systemic manifestations. Myotonic dystrophy type 1 poses a challenge to the anesthesiologist. Those patients are more sensitive to anesthetics and prone to cardiac and pulmonary complications. Besides, the possibility of developing malignant hyperthermia and myotonic episodes is also present. CASE REPORT: This is a 39-year old patient with DM1 who underwent general anesthesia for videolaparoscopic cholecystectomy. Total intravenous

CT findings of muscular dystrophy; Limb girdle type (LG), myotonic type (MYD) and Duchenne type (DMD)

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Saitoh, Hiroshi (Tokushima Univ. (Japan). School of Medicine)

1991-07-01

CT scans of muscles in patients with limb girdle type (LG), myotonic type (MYD) and Duchenne type (DMD) dystrophies were obtained at five different body levels: the neck, L3 vertebral body, pelvic girdle, thigh and lower leg. CT numbers, cross sectional areas (CSA) and %CSA of muscle or fat were evaluated in each muscle. The characteristic CT patterns for each type of muscular dystrophy were obtained. Compared with DMD, the gracilis and soleus were more severely damaged in LG and the biceps femoris remained relatively preserved among the hamstrings. In addition, the multifidus of the neck and sternocleidomastoid also were more severely damaged in MYD. This study suggests that CT scan will be useful in the differential diagnosis of these types of muscular dystrophy as well as in planning appropriate rehabilitation and detecting damaged muscles. (author).

Limb-Girdle Muscular Dystrophy (LGMD)

Science.gov (United States)

... Marie-Tooth Disease (CMT) Congenital Muscular Dystrophy (CMD) Duchenne Muscular Dystrophy (DMD) Emery-Dreifuss Muscular Dystrophy Endocrine Myopathies Metabolic Diseases of Muscle Mitochondrial Myopathies (MM) Myotonic Dystrophy (DM) Spinal-Bulbar ...

Cognitive behavioural therapy with optional graded exercise therapy in patients with severe fatigue with myotonic dystrophy type 1: a multicentre, single-blind, randomised trial.

Science.gov (United States)

Okkersen, Kees; Jimenez-Moreno, Cecilia; Wenninger, Stephan; Daidj, Ferroudja; Glennon, Jeffrey; Cumming, Sarah; Littleford, Roberta; Monckton, Darren G; Lochmüller, Hanns; Catt, Michael; Faber, Catharina G; Hapca, Adrian; Donnan, Peter T; Gorman, Gráinne; Bassez, Guillaume; Schoser, Benedikt; Knoop, Hans; Treweek, Shaun; van Engelen, Baziel G M

2018-06-18

Myotonic dystrophy type 1 is the most common form of muscular dystrophy in adults and leads to severe fatigue, substantial physical functional impairment, and restricted social participation. In this study, we aimed to determine whether cognitive behavioural therapy optionally combined with graded exercise compared with standard care alone improved the health status of patients with myotonic dystrophy type 1. We did a multicentre, single-blind, randomised trial, at four neuromuscular referral centres with experience in treating patients with myotonic dystrophy type 1 located in Paris (France), Munich (Germany), Nijmegen (Netherlands), and Newcastle (UK). Eligible participants were patients aged 18 years and older with a confirmed genetic diagnosis of myotonic dystrophy type 1, who were severely fatigued (ie, a score of ≥35 on the checklist-individual strength, subscale fatigue). We randomly assigned participants (1:1) to either cognitive behavioural therapy plus standard care and optional graded exercise or standard care alone. Randomisation was done via a central web-based system, stratified by study site. Cognitive behavioural therapy focused on addressing reduced patient initiative, increasing physical activity, optimising social interaction, regulating sleep-wake patterns, coping with pain, and addressing beliefs about fatigue and myotonic dystrophy type 1. Cognitive behavioural therapy was delivered over a 10-month period in 10-14 sessions. A graded exercise module could be added to cognitive behavioural therapy in Nijmegen and Newcastle. The primary outcome was the 10-month change from baseline in scores on the DM1-Activ-c scale, a measure of capacity for activity and social participation (score range 0-100). Statistical analysis of the primary outcome included all participants for whom data were available, using mixed-effects linear regression models with baseline scores as a covariate. Safety data were presented as descriptives. This trial is registered

Prenatal molecular diagnosis of inherited neuromuscular diseases: Duchenne/Becker muscular dystrophy, myotonic dystrophy type 1 and spinal muscular atrophy.

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Esposito, Gabriella; Ruggiero, Raffaella; Savarese, Maria; Savarese, Giovanni; Tremolaterra, Maria Roberta; Salvatore, Francesco; Carsana, Antonella

2013-12-01

Neuromuscular disease is a broad term that encompasses many diseases that either directly, via an intrinsic muscle disorder, or indirectly, via a nerve disorder, impairs muscle function. Here we report the experience of our group in the counselling and molecular prenatal diagnosis of three inherited neuromuscular diseases, i.e., Duchenne/Becker muscular dystrophy (DMD/BMD), myotonic dystrophy type 1 (DM1), spinal muscular atrophy (SMA). We performed a total of 83 DMD/BMD, 15 DM1 and 54 SMA prenatal diagnoses using a combination of technologies for either direct or linkage diagnosis. We identified 16, 5 and 10 affected foetuses, respectively. The improvement of analytical procedures in recent years has increased the mutation detection rate and reduced the analytical time. Due to the complexity of the experimental procedures and the high, specific professional expertise required for both laboratory activities and the related counselling, these types of analyses should be preferentially performed in reference molecular diagnostic centres.

T2 relaxometry of brain in myotonic dystrophy

Energy Technology Data Exchange (ETDEWEB)

Di Costanzo, A.; Bonavita, V.; Tedeschi, G. [Inst. of Neurological Sciences, 2. Univ. of Naples (Italy); Di Salle, F. [Dept. of Biomorphological and Functional Sciences, Univ. ' ' Federico II' ' , Naples (Italy); Santoro, L. [Dept. of Neurological Sciences, University ' ' Federico II' ' , Naples (Italy)

2001-03-01

We investigated the nature and extent of brain involvement in myotonic dystrophy (DM), examining possible T2 relaxation abnormalities in the brain of 20 patients with adult-onset DM and 20 sex- and age-matched normal controls. Brain MRI was performed at 0.5 T, and T2 values were calculated from signal intensity in two echoes. Regions of interest included: frontal, parietal, temporal, occipital and callosal (rostral and splenial) normal-appearing white matter; frontal, occipital, insular and hippocampal cortex; caudate nucleus, putamen, globus pallidus and thalamus. All white-matter and occipital and right frontal cortex regions showed a significantly longer T2 in the patients. Multiple regression analysis, including grey- and white-matter T2 as dependent variables, plus age at onset and at imaging, disease duration, muscular disability, brain atrophy and CTG trinucleotide repeats as independent variables, revealed that only white-matter T2 elongation and disease duration correlated positively. White-matter involvement in DM is more extensive than previously reported by MRI and neuropathological studies and seems to be progressive in the course of disease. (orig.)

T2 relaxometry of brain in myotonic dystrophy

International Nuclear Information System (INIS)

Di Costanzo, A.; Bonavita, V.; Tedeschi, G.; Di Salle, F.; Santoro, L.

2001-01-01

We investigated the nature and extent of brain involvement in myotonic dystrophy (DM), examining possible T2 relaxation abnormalities in the brain of 20 patients with adult-onset DM and 20 sex- and age-matched normal controls. Brain MRI was performed at 0.5 T, and T2 values were calculated from signal intensity in two echoes. Regions of interest included: frontal, parietal, temporal, occipital and callosal (rostral and splenial) normal-appearing white matter; frontal, occipital, insular and hippocampal cortex; caudate nucleus, putamen, globus pallidus and thalamus. All white-matter and occipital and right frontal cortex regions showed a significantly longer T2 in the patients. Multiple regression analysis, including grey- and white-matter T2 as dependent variables, plus age at onset and at imaging, disease duration, muscular disability, brain atrophy and CTG trinucleotide repeats as independent variables, revealed that only white-matter T2 elongation and disease duration correlated positively. White-matter involvement in DM is more extensive than previously reported by MRI and neuropathological studies and seems to be progressive in the course of disease. (orig.)

Eosinophilic myositis as first manifestation in a patient with type 2 myotonic dystrophy CCTG expansion mutation and rheumatoid arthritis.

Science.gov (United States)

Meyer, Alain; Lannes, Béatrice; Carapito, Raphaël; Bahram, Seiamak; Echaniz-Laguna, Andoni; Geny, Bernard; Sibilia, Jean; Gottenberg, Jacques Eric

2015-02-01

Eosinophilic myositis is characterized by eosinophilic infiltration of skeletal muscles. In the absence of an identifiable causative factor or source (including parasitic infection, intake of drugs or L-tryptophan, certain systemic disorders as well as malignant diseases), the diagnosis of idiopathic eosinophilic myositis is usually retained. However, some muscular dystrophies have been recently identified in this subset of eosinophilic myositis. Here, we report a patient with an 8 kb CCTG expansion in intron 1 of the CNBP gene, a mutation characteristic of myotonic dystrophy type 2 (DM2), whose first manifestation was "idiopathic" eosinophilic myositis. This report suggests that in "idiopathic" eosinophilic myositis, clinicians should consider muscular dystrophies, including DM2. Copyright © 2014 Elsevier B.V. All rights reserved.

Emerging strategies for cell and gene therapy of the muscular dystrophies

OpenAIRE

Muir, Lindsey A.; Chamberlain, Jeffrey S.

2009-01-01

The muscular dystrophies are a heterogeneous group of over 40 disorders that are characterised by muscle weakness and wasting. The most common are Duchenne muscular dystrophy and Becker muscular dystrophy, which result from mutations within the gene encoding dystrophin; myotonic dystrophy type 1, which results from an expanded trinucleotide repeat in the myotonic dystrophy protein kinase gene; and facioscapulohumeral dystrophy, which is associated with contractions in the subtelomeric region ...

Effects of Functional Electrical Stimulation Lower Extremity Training in Myotonic Dystrophy Type I: A Pilot Controlled Study.

Science.gov (United States)

Cudia, Paola; Weis, Luca; Baba, Alfonc; Kiper, Pawel; Marcante, Andrea; Rossi, Simonetta; Angelini, Corrado; Piccione, Francesco

2016-11-01

Functional electrical stimulation (FES) is a new rehabilitative approach that combines electrical stimulation with a functional task. This pilot study evaluated the safety and effectiveness of FES lower extremity training in myotonic dystrophy type 1. This is a controlled pilot study that enrolled 20 patients with myotonic dystrophy type 1 over 2 years. Eight patients (age, 39-67 years) fulfilled the inclusion criteria. Four participants performed FES cycling training for 15 days (one daily session of 30 minutes for 5 days a week). A control group, matched for clinical and genetic variables, who had contraindications to electrical stimulation, performed 6 weeks of conventional resistance and aerobic training. The modified Medical Research Council Scale and functional assessments were performed before and after treatment. Cohen d effect size was used for statistical analysis. Functional electrical stimulation induced lower extremity training was well tolerated and resulted in a greater improvement of tibialis anterior muscle strength (d = 1,583), overall muscle strength (d = 1,723), and endurance (d = 0,626) than conventional training. Functional electrical stimulation might be considered a safe and valid tool to improve muscle function, also in muscles severely compromised in which no other restorative options are available. Confirmation of FES efficacy through further clinical trials is strongly advised.

Toward a more personalized motor function rehabilitation in Myotonic dystrophy type 1: The role of neuroplasticity.

Directory of Open Access Journals (Sweden)

Simona Portaro

Full Text Available Myotonic dystrophy type 1 (DM1 is the most prevalent adult muscular dystrophy, often accompanied by impairments in attention, memory, visuospatial and executive functions. Given that DM1 is a multi-system disorder, it requires a multi-disciplinary approach, including effective rehabilitation programs, focusing on the central nervous system neuroplasticity, in order to develop patient-tailored rehabilitative procedures for motor function recovery. Herein, we performed a transcranial magnetic stimulation (TMS study aimed at investigating central motor conduction time, sensory-motor plasticity, and cortical excitability in 7 genetically defined DM1 patients. As compared to healthy individuals, DM1 patients showed a delayed central motor conduction time and an abnormal sensory-motor plasticity, with no alteration of cortical excitability. These findings may be useful to define patient-tailored motor rehabilitative programs.

Cognitive behaviour therapy plus aerobic exercise training to increase activity in patients with myotonic dystrophy type 1 (DM1) compared to usual care (OPTIMISTIC): study protocol for randomised controlled trial

NARCIS (Netherlands)

van Engelen, Baziel; Abghari, Shaghayegh; Aschrafi, Armaz; Bouman, Sacha; Cornelissen, Yvonne; Glennon, Jeffrey; Groot, Perry; Heerschap, Arend; Heskamp, Linda; Heskes, Tom; Kapusta, Katarzyna; Klerks, Ellen; Knoop, Hans; Maas, Daphne; Okkersen, Kees; Poelmans, Geert; Rahmadi, Ridho; van Nimwegen, Marlies; Gorman, Grainne; Moreno, Cecilia Jimenez; Lochmüller, Hanns; Trenell, Mike; van Laar, Sandra; Wood, Libby; Schoser, Benedikt; Wenninger, Stephan; Schüller, Angela; Auguston, Mrs Rémie; Baptiste, Lignier; Barau, Caroline; Bassez, Guillaume; Chevalier, Pascale; Couppey, Florence; Delmas, Stéphanie; Deux, Jean-François; Dogan, Celine; Hamadouche, Amira; Hankiewicz, Karolina; Lhermet, Laure; Minier, Lisa; Rialland, Amandine; Schmitz, David; Monckton, Darren G.; Cumming, Sarah A.; Adam, Berit; Donnan, Peter; Hannah, Michael; Hogarth, Fiona; Littleford, Roberta; McKenzie, Emma

2015-01-01

Background: Myotonic dystrophy type 1 (DM1) is a rare, inherited chronic progressive disease as well as an autosomal dominant multi-systemic disorder. It is probably one of the most common adult forms of muscular dystrophy, with a prevalence of approximately 10 per 100,000 people affected. With 733

Cognitive behaviour therapy plus aerobic exercise training to increase activity in patients with myotonic dystrophy type 1 (DM1) compared to usual care (OPTIMISTIC): study protocol for randomised controlled trial

NARCIS (Netherlands)

Engelen, B.G.M. van; Groot, P.C.; Abghari, S.; Aschrafi, A.; Bouman, S.F.; Cornelissen, Y.; Glennon, J.C.; Heerschap, A.; Heskamp, L.; Heskes, T.M.; Kapusta, K.A.; Klerks, E.; Knoop, H.; Maas, D; Okkersen, C.P.; Poelmans, G.J.V.; Rahmadi, R.; Nimwegen, M. van; et al.,

2015-01-01

BACKGROUND: Myotonic dystrophy type 1 (DM1) is a rare, inherited chronic progressive disease as well as an autosomal dominant multi-systemic disorder. It is probably one of the most common adult forms of muscular dystrophy, with a prevalence of approximately 10 per 100,000 people affected. With 733

Endocrine function over time in patients with myotonic dystrophy type 1

DEFF Research Database (Denmark)

Dahlqvist, Julia Rebecka; Ørngreen, M C; Witting, N

2015-01-01

BACKGROUND AND PURPOSE: Patients with myotonic dystrophy type 1 (DM1) have an increased incidence of endocrine dysfunction. In this study, the temporal evolution of endocrine dysfunction in patients with DM1 was investigated. METHODS: Endocrine function was assessed in 68 patients with DM1, in whom...... endocrine function had been followed, on average, for 8 years. The endocrine function was assessed by measuring the concentration of hormones and metabolites in blood and by validating libido with questionnaires. RESULTS: At baseline, 30 of the 68 patients presented with at least one hormonal dysfunction....... When re-evaluated after 8 years, 57 of 68 patients had endocrine dysfunction. Diabetic patients had increased from one to four. At follow-up, hyperparathyroidism occurred in 25% and abnormal thyroid-stimulating hormone in 21%, compared with 14% and 9% at baseline. Sixteen of 33 men had increased...

Association of peripheral neuropathy with sleep-related breathing disorders in myotonic dystrophies

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Banach M

2017-01-01

Full Text Available Marta Banach,1,* Jakub Antczak,1,* Rafał Rola21Department of Clinical Neurophysiology, 2First Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland *These authors contributed equally to this workBackground: Myotonic dystrophy (DM type 1 and type 2 are inherited diseases characterized by myotonia and myopathy. Additional symptoms include, among others, peripheral neuropathy and sleep-related breathing disorders (SRBDs. There is growing evidence for a complex association between DM1 and DM2, which was described in patients with diabetes mellitus and in the general population. In this study, we investigated whether there is an association between peripheral neuropathy and SRBDs also in the population of patients with DM.Methods: The study included 16 patients with DM1 (mean age, 37.9±14.1 years; 20–69 years and eight patients with DM2 (mean age, 47.6±14.1 years; 20–65 years, who underwent a sensory and motor nerve conduction study (NCS and diagnostic screening for SRBDs. In both groups, the NCS parameters were correlated with respiratory parameters.Results: In both groups, the amplitude of the ulnar sensory nerve action potential (SNAP correlated with the mean arterial oxygen saturation (SaO2. In addition, in the DM2 group, the median SNAP correlated with the mean SaO2. In the DM1 group, the median SNAP and the distal motor latency (DML of the ulnar nerve correlated with the apnea–hypopnea index, while the oxygen desaturation index correlated with the DML of the tibial nerve and with conduction velocity in the sural nerve.Conclusion: Our results indicate a complex association between neuropathy and SRBDs in DM1 and DM2. Axonal degeneration may contribute to nocturnal hypoxemia and vice versa. Neuropathy may contribute to muscle weakness, which in turn may cause respiratory events.Keywords: myotonic dystrophy, SRBD and neuropathy with AHI, SNAP, CMAP

Redefining the non-dystrophic myotonic syndromes. Phenotypic characterisation based on genetic testing.

NARCIS (Netherlands)

Trip, J.

2010-01-01

Chapter 1 gives a general introduction to non-dystrophic myotonic syndromes (NDMs). Chapter 2 comprises a systematic review about drug treatment for myotonia. Three small crossover studies evaluated myotonia in myotonic dystrophy. Unfortunately, for the treatment of myotonia in NDMs we were unable

Steinert syndrome and repercussions in dental medicine.

Science.gov (United States)

Baptista, Helena; Lopes Cardoso, Inês

2017-03-01

Steinert syndrome, also called myotonic dystrophy type 1, is a genetic disorder with autosomal dominant transmission characterized by myotonia and a multisystemic clinical picture that affects several tissues of the human body. The most common systemic phenotypes are: muscular, cardiac, respiratory, CNS, ocular, gynecological, digestive, orthopedical, as well as cognitive and psychological symptoms (cognitive decline). Muscles involved in voluntary movement are highly affected by myotonia especially distal muscles of upper limbs. These patients also show changes in face, chewing and pharynx muscles that can lead to swallowing and speech problems, dysphagia and in most cases to food aspiration and suffocation. Poor oral hygiene resulting from reduced motor mobility and reduced saliva flux can lead to gingival inflammation and periodontal disease. Other oral manifestations include disturbances at the temporomandibular articulation, dental occlusion changes and reduction in teeth number as a result of caries. Main causes of death are pneumonia and cardiac arrhythmias. The etiopathogeny of this syndrome is still not clear, conditioning the existence of a specific treatment for this disease. Nowadays, treatments consist on the release of the existing symptoms, in an attempt to give a better life quality to patients. It is very important to implement actions that can prevent complications and consequently decrease death. Treatments should be applied in an early stage of the disease. Bronchoscopy and artificial respiration should be used to prevent pneumonia, and regular electrocardiographic monitoring should be done to evaluate defects in the conductive system. Several approaches have been applied to rehabilitate swallowing dysfunction and avoid aspiration like videofluoroscopy, postural techniques and adjustment of diet type. It is the aim of this paper to clarify the ethiology, diagnosis, systemic and oral characteristics of the syndrome, as well as to discuss

Treatment of sleep central apnea with non-invasive mechanical ventilation with 2 levels of positive pressure (bilevel in a patient with myotonic dystrophy type 1

Directory of Open Access Journals (Sweden)

Ricardo Tera Akamine

2014-06-01

Bi-level positive airway pressure treatment at spontaneous/timed mode showed an improvement in snoring, apneas, and Epworth sleepiness scale decreased from 20 to 10. This case illustrates the beneficial effects of Bi-level positive airway pressure support in central sleep apnea syndrome of a patient with myotonic dystrophy type 1.

A Population-based survey of risk for cancer in individuals diagnosed with myotonic dystrophy

Science.gov (United States)

Abbott, Diana; Johnson, Nicholas E; Cannon-Albright, Lisa A.

2018-01-01

Introduction The risk of cancer in patients diagnosed with myotonic dystrophy (DM) is reported for the homogeneous Utah population. Methods Clinical data accessed from the largest Utah healthcare providers have been record-linked to the Utah Population Database (UPDB), a population-based resource also linked to the Utah Cancer Registry. Relative risks were estimated for 36 cancers of different types in 281 DM patients. Results Testicular cancer (RR=10.74; 95% CI: 1.91, 38.79), endometrial cancer (6.98; 1.24, 25.22), and Non-Hodgkins lymphoma (4.25; 1.16, 12.43) were all observed at significant excess in DM patients. Discussion This study confirms an overall increased risk of cancer in DM. Individuals diagnosed with DM might benefit from risk counseling. PMID:27064430

Targeting DMPK with Antisense Oligonucleotide Improves Muscle Strength in Myotonic Dystrophy Type 1 Mice

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Dominic Jauvin

2017-06-01

Full Text Available Myotonic dystrophy type 1 (DM1, a dominant hereditary muscular dystrophy, is caused by an abnormal expansion of a (CTGn trinucleotide repeat in the 3′ UTR of the human dystrophia myotonica protein kinase (DMPK gene. As a consequence, mutant transcripts containing expanded CUG repeats are retained in nuclear foci and alter the function of splicing regulatory factors members of the MBNL and CELF families, resulting in alternative splicing misregulation of specific transcripts in affected DM1 tissues. In the present study, we treated DMSXL mice systemically with a 2′-4′-constrained, ethyl-modified (ISIS 486178 antisense oligonucleotide (ASO targeted to the 3′ UTR of the DMPK gene, which led to a 70% reduction in CUGexp RNA abundance and foci in different skeletal muscles and a 30% reduction in the heart. Furthermore, treatment with ISIS 486178 ASO improved body weight, muscle strength, and muscle histology, whereas no overt toxicity was detected. This is evidence that the reduction of CUGexp RNA improves muscle strength in DM1, suggesting that muscle weakness in DM1 patients may be improved following elimination of toxic RNAs.

Targeting DMPK with Antisense Oligonucleotide Improves Muscle Strength in Myotonic Dystrophy Type 1 Mice.

Science.gov (United States)

Jauvin, Dominic; Chrétien, Jessina; Pandey, Sanjay K; Martineau, Laurie; Revillod, Lucille; Bassez, Guillaume; Lachon, Aline; MacLeod, A Robert; Gourdon, Geneviève; Wheeler, Thurman M; Thornton, Charles A; Bennett, C Frank; Puymirat, Jack

2017-06-16

Myotonic dystrophy type 1 (DM1), a dominant hereditary muscular dystrophy, is caused by an abnormal expansion of a (CTG) n trinucleotide repeat in the 3' UTR of the human dystrophia myotonica protein kinase (DMPK) gene. As a consequence, mutant transcripts containing expanded CUG repeats are retained in nuclear foci and alter the function of splicing regulatory factors members of the MBNL and CELF families, resulting in alternative splicing misregulation of specific transcripts in affected DM1 tissues. In the present study, we treated DMSXL mice systemically with a 2'-4'-constrained, ethyl-modified (ISIS 486178) antisense oligonucleotide (ASO) targeted to the 3' UTR of the DMPK gene, which led to a 70% reduction in CUG exp RNA abundance and foci in different skeletal muscles and a 30% reduction in the heart. Furthermore, treatment with ISIS 486178 ASO improved body weight, muscle strength, and muscle histology, whereas no overt toxicity was detected. This is evidence that the reduction of CUG exp RNA improves muscle strength in DM1, suggesting that muscle weakness in DM1 patients may be improved following elimination of toxic RNAs. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Prediction of myotonic dystrophy clinical severity based on the number of intragenic [CTG]{sub n} trinucleotide repeats

Energy Technology Data Exchange (ETDEWEB)

Gennarelli, M.; Dallapiccola, B. [Universita Tor Vergata, Rome (Italy); Novelli, G. [Universita Cattolica del Sacro Cuore, Rome (Italy)] [and others

1996-11-11

We carried out a genotype-phenotype correlation study, based on clinical findings in 465 patients with myotonic dystrophy (DM), in order to assess [CTG] repeat number as a predictive test of disease severity. Our analysis showed that the DM subtypes defined by strict clinical criteria fall into three different classes with a log-normal distribution. This distribution is useful in predicting the probability of specific DM phenotypes based on triplet [CTG] number. This study demonstrates that measurement of triplet expansions in patients` lymphocyte DNA is highly valuable and accurate for prognostic assessment. 45 refs., 1 fig., 2 tabs.

Sensitivity to Rocuronium-Induced Neuromuscular Block and Reversibility with Sugammadex in a Patient with Myotonic Dystrophy

Directory of Open Access Journals (Sweden)

Akihiro Kashiwai

2012-01-01

Full Text Available We report a patient with myotonic dystrophy who showed prolonged rocuronium-induced neuromuscular blockade, although with a fast recovery with sugammadex. During general anesthesia with propofol and remifentanil, the times to spontaneous recovery of the first twitch (T1 of train of four to 10% of control values after an intubating dose of rocuronium 1 mg/kg and an additional dose of 0.2 mg/kg were 112 min and 62 min, respectively. Despite the high sensitivity to rocuronium, sugammadex 2 mg/kg administered at a T1 of 10% safely and effectively antagonized rocuronium-induced neuromuscular block in 90 s.

Prevalence and correlates of apathy in myotonic dystrophy type 1.

Science.gov (United States)

Gallais, Benjamin; Montreuil, Michèle; Gargiulo, Marcela; Eymard, Bruno; Gagnon, Cynthia; Laberge, Luc

2015-08-22

Apathy in DM1 has long been acknowledged in clinical practice. However, a major drawback is that the concept has been only sparsely explored in previous specific studies. This study aimed to determine the prevalence of apathy in myotonic dystrophy (DM1), to compare it with facioscapulohumeral dystrophy (FSHD) patients and normal healthy controls, and explore its relationship to psychopathological features and cognitive function. Levels of apathy in 38 DM1 patients with adult phenotypes were compared with 19 patients with FSHD and 20 matched controls. Patient participants were consecutively recruited, regarding their interdisciplinary annual evaluation at the neuromuscular pathology reference center (Institute of Myology, Paris, France), within an 18-month period. Additional measurements included motor disability, fatigue, depression, anxiety, and cognitive abilities. Inter-group comparisons were performed using non-parametric Kruskal-Wallis tests and Mann-Whitney U Tests. Intra-group comparisons were carried out with the Wilcoxon Signed rank and Friedman tests. Also, Spearman's correlations were used to assess the strength of linear relationships between pairs of variables. The significance level was set at 0.05. Global score of apathy was significantly higher in DM1 patients than in FSHD patients (p fatigue, depression, and anxiety. Apathy is a frequent symptom in DM1 (almost 40 %). It is more prevalent than in a similarly disabled group of patients with FSHD and in controls. Results also show that apathy in DM1 is independent of the psychopathological domain, fatigue, age, and motor disability, but associated to general cognitive status. These results altogether could suggest a central cause for apathy in DM1 rather than an adjustment process to cope with the progressive and debilitating nature of the disease. Data emphasize the importance to evaluate this symptom in routine clinical management of DM1 patients.

MBNL Sequestration by Toxic RNAs and RNA Misprocessing in the Myotonic Dystrophy Brain

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Marianne Goodwin

2015-08-01

Full Text Available For some neurological disorders, disease is primarily RNA mediated due to expression of non-coding microsatellite expansion RNAs (RNAexp. Toxicity is thought to result from enhanced binding of proteins to these expansions and depletion from their normal cellular targets. However, experimental evidence for this sequestration model is lacking. Here, we use HITS-CLIP and pre-mRNA processing analysis of human control versus myotonic dystrophy (DM brains to provide compelling evidence for this RNA toxicity model. MBNL2 binds directly to DM repeat expansions in the brain, resulting in depletion from its normal RNA targets with downstream effects on alternative splicing and polyadenylation. Similar RNA processing defects were detected in Mbnl compound-knockout mice, highlighted by dysregulation of Mapt splicing and fetal tau isoform expression in adults. These results demonstrate that MBNL proteins are directly sequestered by RNAexp in the DM brain and introduce a powerful experimental tool to evaluate RNA-mediated toxicity in other expansion diseases.

Functioning and disability in adults with myotonic dystrophy type 1.

Science.gov (United States)

Kierkegaard, Marie; Harms-Ringdahl, Karin; Holmqvist, Lotta Widén; Tollbäck, Anna

2011-01-01

 To provide a comprehensive description of functioning and disability with regard to stages of disease progression in adults with myotonic dystrophy type 1 (DM1). Further to explore associations of measures of manual dexterity and of walking capacity with measures of activities of daily living (ADL) and participation in social and lifestyle activities. Seventy persons with DM1 underwent examinations, tests and answered questionnaires. Stages of disease progression were based on the muscular impairment rating scale.  Overweight, cardiac dysfunctions, respiratory restrictions, fatigue and/or low physical activity levels were found in approximately 40% of those with DM1. Over 75% had muscle impairments, and activity limitations in manual dexterity and walking. Dependence in personal and instrumental ADL was found in 16% and 39%, respectively, and participation restrictions in social and lifestyle activities in 52%. The presence of concurrent body-function impairments, activity limitations and participation restrictions was high. Significant differences were found in muscle impairment, manual dexterity, mobility, ADL and social and lifestyle activities with regard to disease progression. Cut-off values in measures of manual dexterity and walking capacity associated to functioning are proposed.  This information can be used for developing clinical practise and for health promotion for persons with DM1.

The clinical and genetic correlates of MRI findings in myotonic dystrophy

International Nuclear Information System (INIS)

Bachmann, G.; Damian, M.S.; Koch, M.; Schilling, G.; Fach, B.; Stoeppler, S.

1996-01-01

Amplification of an unstable CTG trinucleotide repeat sequence in a protein kinase gene on chromosome 19 has recently been recognised as the molecular basis of myotonic dystrophy (DM), a multisystem disorder with a wide spectrum of muscular and extramuscular manifestations. The CTG expansion of 40 patients was assessed by direct genotype analysis of the white blood cell DNA and correlated with MRI of the brain and muscles, and with functional clinical data. Cerebral pathology on MRI consisted of diffuse atrophy (68 %), subcortical white matter lesions (65 %), wide Virchow-Robin spaces (38 %) and thickening of the skull (35 %). Cerebral atrophy and extent of white matter disease correlated significantly with mental retardation, duration of disease and CTG fragment amplification. MRI of the muscular system showed fatty degeneration of different degrees in neighbouring muscles causing a mosaic pattern of the thigh in 38 % and the calf in 44 %. Muscular changes on MRI were strongly correlated with muscular impairment but less strongly with CTG expansion. Changes on MRI reflect the stage of development of tissue pathology in DM, modified by defect of the DM gene. Pathology on MRI is strongly correlated with functional deficits. (orig.). With 8 figs., 3 tabs

Abnormal splicing switch of DMD's penultimate exon compromises muscle fibre maintenance in myotonic dystrophy.

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Rau, Frédérique; Lainé, Jeanne; Ramanoudjame, Laetitita; Ferry, Arnaud; Arandel, Ludovic; Delalande, Olivier; Jollet, Arnaud; Dingli, Florent; Lee, Kuang-Yung; Peccate, Cécile; Lorain, Stéphanie; Kabashi, Edor; Athanasopoulos, Takis; Koo, Taeyoung; Loew, Damarys; Swanson, Maurice S; Le Rumeur, Elisabeth; Dickson, George; Allamand, Valérie; Marie, Joëlle; Furling, Denis

2015-05-28

Myotonic Dystrophy type 1 (DM1) is a dominant neuromuscular disease caused by nuclear-retained RNAs containing expanded CUG repeats. These toxic RNAs alter the activities of RNA splicing factors resulting in alternative splicing misregulation and muscular dysfunction. Here we show that the abnormal splicing of DMD exon 78 found in dystrophic muscles of DM1 patients is due to the functional loss of MBNL1 and leads to the re-expression of an embryonic dystrophin in place of the adult isoform. Forced expression of embryonic dystrophin in zebrafish using an exon-skipping approach severely impairs the mobility and muscle architecture. Moreover, reproducing Dmd exon 78 missplicing switch in mice induces muscle fibre remodelling and ultrastructural abnormalities including ringed fibres, sarcoplasmic masses or Z-band disorganization, which are characteristic features of dystrophic DM1 skeletal muscles. Thus, we propose that splicing misregulation of DMD exon 78 compromises muscle fibre maintenance and contributes to the progressive dystrophic process in DM1.

Using digital technologies to engage with medical research: views of myotonic dystrophy patients in Japan.

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Coathup, Victoria; Teare, Harriet J A; Minari, Jusaku; Yoshizawa, Go; Kaye, Jane; Takahashi, Masanori P; Kato, Kazuto

2016-08-24

As in other countries, the traditional doctor-patient relationship in the Japanese healthcare system has often been characterised as being of a paternalistic nature. However, in recent years there has been a gradual shift towards a more participatory-patient model in Japan. With advances in technology, the possibility to use digital technologies to improve patient interactions is growing and is in line with changing attitudes in the medical profession and society within Japan and elsewhere. The implementation of an online patient engagement platform is being considered by the Myotonic Dystrophy Registry of Japan. The aim of this exploratory study was to understand patients' views and attitudes to using digital tools in patient registries and engagement with medical research in Japan, prior to implementation of the digital platform. We conducted an exploratory, cross-sectional, self-completed questionnaire with a sample of myotonic dystrophy (MD) patients attending an Open Day at Osaka University, Japan. Patients were eligible for inclusion if they were 18 years or older, and were diagnosed with MD. A total of 68 patients and family members attended the Open Day and were invited to participate in the survey. Of those, 59 % submitted a completed questionnaire (n = 40). The survey showed that the majority of patients felt that they were not receiving the information they wanted from their clinicians, which included recent medical research findings and opportunities to participate in clinical trials, and 88 % of patients indicated they would be willing to engage with digital technologies to receive relevant medical information. Patients also expressed an interest in having control over when and how they received this information, as well as being informed of how their data is used and shared with other researchers. Overall, the findings from this study suggest that there is scope to develop a digital platform to engage with patients so that they can receive

Pain in patients with myotonic dystrophy type 2: a postal survey in Finland.

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Suokas, Kimmo I; Haanpää, Maija; Kautiainen, Hannu; Udd, Bjarne; Hietaharju, Aki J

2012-01-01

Widespread musculoskeletal pain is a well-known symptom of myotonic dystrophy type 2 (DM2), but so far it has been addressed in only a few studies. A postal survey for all traceable DM2 patients (n = 132) was conducted. A specific questionnaire, and severity and interference subscales of the Brief Pain Inventory, quality of life (RAND-36), and modified Beck Depression Inventory were completed. The response rate was 70%. The mean age of respondents was 53 years, 59% of whom were women. Current pain was reported by 54%. Lifetime prevalence of pain was 76%. The mean intensity of pain at its highest in the last week was 5.9, and 2.3 at its lowest (on a numerical rating scale of 0-10). Quality of life was lower in DM2 patients who reported pain. In 18%, the depression score was noticeably different. Pain of moderate severity and unpleasant muscular symptoms are common in DM2. DM2 should be taken into consideration in the differential diagnosis of musculoskeletal pain. Copyright © 2011 Wiley Periodicals, Inc.

Balance outcomes following a tap dance program for a child with congenital myotonic muscular dystrophy.

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Biricocchi, Charlanne; Drake, JaimeLynn; Svien, Lana

2014-01-01

This case report describes the effects of a 6-week progressive tap dance program on static and dynamic balance for a child with type 1 congenital myotonic muscular dystrophy (congenital MMD1). A 6-year-old girl with congenital MMD1 participated in a 1-hour progressive tap dance program. Classes were held once a week for 6 consecutive weeks and included 3 children with adaptive needs and 1 peer with typical development. The Bruininks-Oseretsky Test of Motor Proficiency, second edition (BOT-2) balance subsection and the Pediatric Balance Scale were completed at the beginning of the first class and the sixth class. The participant's BOT-2 score improved from 3 to 14. Her Pediatric Balance Scale score did not change. Participation in a progressive tap dance class by a child with congenital MMD1 may facilitate improvements in static and dynamic balance.

Treatment of sleep central apnea with non-invasive mechanical ventilation with 2 levels of positive pressure (bilevel) in a patient with myotonic dystrophy type 1

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Ricardo Tera Akamine; Luís Fernando Grossklauss; Gustavo Antonio Moreira; Marcia Pradella-Hallinan; Marco Antônio Chiéia; Denis Mesquita; Acary Souza Bulle Oliveira; Sergio Tufik

2014-01-01

We are reporting a case of a 29 year-old female with diagnosis of myotonic dystrophy type 1 (Steinert’s disease) with excessive daytime sleepiness, muscle fatigue, snoring, frequent arousals, non-restorative sleep, and witnessed apneas. Pulmonary function tests revealed a mild decrease of forced vital capacity. Nocturnal polysomnography showed an increase of apnea/hypopnea index (85.9 events/h), mainly of central type (236), minimal oxygen saturation of 72%, and end-tidal carbon dioxide value...

Brain gray matter structural network in myotonic dystrophy type 1.

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Atsuhiko Sugiyama

Full Text Available This study aimed to investigate abnormalities in structural covariance network constructed from gray matter volume in myotonic dystrophy type 1 (DM1 patients by using graph theoretical analysis for further clarification of the underlying mechanisms of central nervous system involvement. Twenty-eight DM1 patients (4 childhood onset, 10 juvenile onset, 14 adult onset, excluding three cases from 31 consecutive patients who underwent magnetic resonance imaging in a certain period, and 28 age- and sex- matched healthy control subjects were included in this study. The normalized gray matter images of both groups were subjected to voxel based morphometry (VBM and Graph Analysis Toolbox for graph theoretical analysis. VBM revealed extensive gray matter atrophy in DM1 patients, including cortical and subcortical structures. On graph theoretical analysis, there were no significant differences between DM1 and control groups in terms of the global measures of connectivity. Betweenness centrality was increased in several regions including the left fusiform gyrus, whereas it was decreased in the right striatum. The absence of significant differences between the groups in global network measurements on graph theoretical analysis is consistent with the fact that the general cognitive function is preserved in DM1 patients. In DM1 patients, increased connectivity in the left fusiform gyrus and decreased connectivity in the right striatum might be associated with impairment in face perception and theory of mind, and schizotypal-paranoid personality traits, respectively.

Role of myotonic dystrophy protein kinase (DMPK in glucose homeostasis and muscle insulin action.

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Esther Llagostera

2007-11-01

Full Text Available Myotonic dystrophy 1 (DM1 is caused by a CTG expansion in the 3'-unstranslated region of the DMPK gene, which encodes a serine/threonine protein kinase. One of the common clinical features of DM1 patients is insulin resistance, which has been associated with a pathogenic effect of the repeat expansions. Here we show that DMPK itself is a positive modulator of insulin action. DMPK-deficient (dmpk-/- mice exhibit impaired insulin signaling in muscle tissues but not in adipocytes and liver, tissues in which DMPK is not expressed. Dmpk-/- mice display metabolic derangements such as abnormal glucose tolerance, reduced glucose uptake and impaired insulin-dependent GLUT4 trafficking in muscle. Using DMPK mutants, we show that DMPK is required for a correct intracellular trafficking of insulin and IGF-1 receptors, providing a mechanism to explain the molecular and metabolic phenotype of dmpk-/- mice. Taken together, these findings indicate that reduced DMPK expression may directly influence the onset of insulin-resistance in DM1 patients and point to dmpk as a new candidate gene for susceptibility to type 2-diabetes.

Effects of hand-training in persons with myotonic dystrophy type 1--a randomised controlled cross-over pilot study.

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Aldehag, Anna; Jonsson, Hans; Lindblad, Jan; Kottorp, Anders; Ansved, Tor; Kierkegaard, Marie

2013-10-01

To investigate the effects of a hand-training programme on grip, pinch and wrist force, manual dexterity and activities of daily living, in adults with myotonic dystrophy type 1 (DM1). In this randomised controlled trial with a crossover design, 35 adults with DM1 were, after stratification for grip force, assigned by lot to two groups. Group A started with 12 weeks of hand training, while group B had no intervention. After a wash-out period of 12 weeks, where none received training, the order was reversed. The Grippit® was used as primary outcome measure and the hand-held Microfet2™ myometer, the Purdue Pegboard, the Canadian Occupational Performance Measure (COPM) and the Assessment of Motor and Process Skills (AMPS) were secondary outcome measures. Assessments were performed before and after training and control periods, i.e. four times altogether. Ten persons dropped out and 13 had acceptable adherence. Intention-to-treat analyses revealed significant intervention effects for isometric wrist flexor force (p = 0.048), and for COPM performance (p = 0.047) and satisfaction (p = 0.027). On an individual level, improvements were in general showed after a training period. The hand-training programme had positive effects on wrist flexor force and self-perception of occupational performance, and of satisfaction with performance. No evident detrimental effects were shown. Myotonic dystrophy type 1 (DM1) is a slowly progressive neuromuscular disease characterised by myotonia and muscle weakness and wasting. People with DM1 are often concerned about their ability to carry out ADL and to participate in, e.g. work, sports and hobbies when they gradually become weaker. This pilot study showed that a hand-training programme improved wrist flexor force and self-perception and satisfaction of occupational performance. Resistance training of hand muscles with a silicon-based putty can be a therapy option for people with DM1 in clinical practise.

Erythrocytes in muscular dystrophy. Investigation with 31P nuclear magnetic resonance spectroscopy

International Nuclear Information System (INIS)

Sarpel, G.; Lubansky, H.J.; Danon, M.J.; Omachi, A.

1981-01-01

Phosphorus 31 nuclear magnetic resonance ( 31 P NMR) signals were recorded from intact human erythrocytes for 16 hours. Total phosphate concentration, which was estimated as the sum of the individual 31 P signals, was 25% lower in erythrocytes from men with myotonic dystrophy than in control erythrocytes. The inorganic-phosphate fraction contained the highest average phosphate concentration over the 16-hour period, and made the major contribution to the difference in total phosphate between the two groups. This result was not observed in erythrocytes from either women with myotonic dystrophy or patients with Duchenne's dystrophy and may be due to a change in cell membrane permeability to inorganic phosphate, which leads to lower steady-state concentrations of the intracellular phosphates

Erythrocytes in muscular dystrophy. Investigation with 31P nuclear magnetic resonance spectroscopy

International Nuclear Information System (INIS)

Sarpel, G.; Lubansky, H.J.; Danon, M.J.; Omachi, A.

1981-01-01

Phosphorus 31 nuclear magnetic resonance (31P NMR) signals were recorded from intact human erythrocytes for 16 hours. Total phosphate concentration, which was estimated as the sum of the individual 31P signals, was 25% lower in erythrocytes from men with myotonic dystrophy than in control erythrocytes. The inorganic-phosphate fraction contained the highest average phosphate concentration over the 16-hour period, and made the major contribution to the difference in total phosphate between the two groups. This result was not observed in erythrocytes from either women with myotonic dystrophy or patients with Duchenne's dystrophy and may be due to a change in cell membrane permeability to inorganic phosphate, which lead to lower steady-state concentrations of the intracellular phosphates

NMR Spectroscopy and Molecular Dynamics Simulation of r(CCGCUGCGG)2 Reveal a Dynamic UU Internal Loop Found in Myotonic Dystrophy Type 1†

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Parkesh, Raman; Fountain, Matthew; Disney, Matthew D.

2011-01-01

The NMR structure of an RNA with a copy of the 5′CUG/3′GUC motif found in the triplet repeating disorder myotonic dystrophy type 1 (DM1) is disclosed. The lowest energy conformation of the UU pair is a single hydrogen bonded structure; however, the UU protons undergo exchange indicating structural dynamics. Molecular dynamics simulations show that the single hydrogen bonded structure is the most populated one but the UU pair interconverts between 0, 1, and 2 hydrogen bonded pairs. These studies have implications for the recognition of the DM1 RNA by small molecules and proteins. PMID:21204525

Expanded [CCTG]n repetitions are not associated with abnormal methylation at the CNBP locus in myotonic dystrophy type 2 (DM2) patients.

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Santoro, Massimo; Fontana, Luana; Maiorca, Francesca; Centofanti, Federica; Massa, Roberto; Silvestri, Gabriella; Novelli, Giuseppe; Botta, Annalisa

2018-03-01

Myotonic Dystrophy type 2 (DM2) is a multisystemic disorder associated with an expanded [CCTG]n repeat in intron 1 of the CNBP gene. Epigenetic modifications have been reported in many repeat expansion disorders, including myotonic dystrophy type 1 (DM1), either as a mechanism to explain somatic repeat instability or transcriptional alterations in disease genes. The purpose of our work was to determine the effect of DM2 mutation on the methylation status of CpG islands localized in the 5' promoter region and in the 3' end of the [CCTG]n expansion of the CNBP gene. By bisulfite pyrosequencing, we characterized the methylation profile of two different CpG islands within these regions, either in whole blood and skeletal muscle tissues of DM2 patients (n=72 and n=7, respectively) and controls (n=50 and n=7, respectively). Moreover, we compared the relative mRNA transcript levels of CNBP gene in leukocytes and in skeletal muscle tissues from controls and DM2 patients. We found that CpG sites located in the promoter region showed hypomethylation, whereas CpG sites at 3' end of the CCTG array are hypermethylated. Statistical analyses did not demonstrate any significant differences in the methylation profile between DM2 patients and controls in both tissues analyzed. According to the methylation analysis, CNBP gene expression levels are not significantly altered in DM2 patients. These results show that [CCTG]n repeat expansion, differently from the DM1 mutation, does not influence the methylation status of the CNBP gene and suggest that other molecular mechanisms are involved in the pathogenesis of DM2. Copyright © 2018 Elsevier B.V. All rights reserved.

[Combined spinal-epidural anesthesia for cesarean section in a parturient with myotonic dystrophy].

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Mori, Kosuke; Mizuno, Ju; Nagaoka, Takehiko; Harashima, Toshiya; Morita, Sigeho

2010-08-01

Myotonic dystrophy (MD) is a muscle disorder characterized by progressive muscle wasting and weakness, and is the most common form of muscular dystrophy that begins in adulthood, often after pregnancy. MD might be related to occurrence of malignant hyperthermia. Therefore, the cesarean section is often performed for the parturient with MD. We had an experience of combined spinal-epidural anesthesia for cesarean section in a parturient complicated with MD. A 40-year-old woman had rhabdomyolysis caused by ritodrine at 15-week gestation and was diagnosed as MD by electromyography. Her first baby died due to respiratory failure fourth day after birth. She had hatchet face, slight weakness of her lower extremities, and easy fatigability. Her manual muscle test was 5/5 at upper extremities and 4/5 at lower extremities. She underwent emergency cesarean section for premature rupture of the membrane, weak pain during labor, and obstructed labor at 33-week gestation. We placed an epidural catheter from T12/L1 and punctured arachnoid with 25 G spinal needle. We performed spinal anesthesia using 0.5% hyperbaric bupivacaine 1.5 ml and epidural anesthesia using 2% lidocaine 6 ml. Her anesthetic level reached bilaterally to T7 and operation started 18 minutes after combined spinal-epidural anesthesia. Her baby was born 23 minutes after the anesthesia. As her baby was 1/5 at Apgar score, the baby was tracheally intubated and artificially ventilated. The cesarean section was finished in 33 minutes uneventfully. She had no adverse events and was discharged on the 8th postoperative day. Later her baby was diagnosed as congenital MD by gene analysis. Combined spinal-epidural anesthesia with the amide-typed local anesthetic agents could be useful and safe for cesarean section in the parturient with MD.

Clinical and electromyographic criteria for the diagnosis of hereditary myotonic syndromes

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V. P. Fedotov

2012-01-01

Full Text Available Hereditary myotonic syndromes (HMS are a group of genetically heterogeneous diseases of the chlorine and sodium ion channels (channelopathies with evident clinical polymorphism and high prevalence in the population. The differential diagnosis of early‑stage NMS poses a challenge to clinicians to this day. The investigation has attempted to elaborate informative differentiating criteria on the basis of a clinical and electromyographic study of 2 groups of patients with hereditary Thomsen or Becker myotonia (n = 45 and myotonic dystrophy type 1 (n = 39 verified by DNA analysis of the CLCN1 and DMPK genes. Along with the clinical symptoms, there may be the value of M‑response amplitude decrement in rhythmic stimulation of the n. ulnaris and the duration of myotonic discharges at pin electromyography of the m. tibialis anterior.

Abnormal functional brain connectivity and personality traits in myotonic dystrophy type 1.

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Serra, Laura; Silvestri, Gabriella; Petrucci, Antonio; Basile, Barbara; Masciullo, Marcella; Makovac, Elena; Torso, Mario; Spanò, Barbara; Mastropasqua, Chiara; Harrison, Neil A; Bianchi, Maria L E; Giacanelli, Manlio; Caltagirone, Carlo; Cercignani, Mara; Bozzali, Marco

2014-05-01

Myotonic dystrophy type 1 (DM1), the most common muscular dystrophy observed in adults, is a genetic multisystem disorder affecting several other organs besides skeletal muscle, including the brain. Cognitive and personality abnormalities have been reported; however, no studies have investigated brain functional networks and their relationship with personality traits/disorders in patients with DM1. To use resting-state functional magnetic resonance imaging to assess the potential relationship between personality traits/disorders and changes to functional connectivity within the default mode network (DMN) in patients with DM1. We enrolled 27 patients with genetically confirmed DM1 and 16 matched healthy control individuals. Patients underwent personality assessment using clinical interview and Minnesota Multiphasic Personality Inventory-2 administration; all participants underwent resting-state functional magnetic resonance imaging. Investigations were conducted at the Istituto di Ricovero e Cura a Carattere Scientifico Santa Lucia Foundation, Catholic University of Sacred Heart, and Azienda Ospedaliera San Camillo Forlanini. Resting-state functional magnetic resonance imaging. Measures of personality traits in patients and changes in functional connectivity within the DMN in patients and controls. Changes in functional connectivity and atypical personality traits in patients were correlated. We combined results obtained from the Minnesota Multiphasic Personality Inventory-2 and clinical interview to identify a continuum of atypical personality profiles ranging from schizotypal personality traits to paranoid personality disorder within our DM1 patients. We also demonstrated an increase in functional connectivity in the bilateral posterior cingulate and left parietal DMN nodes in DM1 patients compared with controls. Moreover, patients with DM1 showed strong associations between DMN functional connectivity and schizotypal-paranoid traits. Our findings provide novel

CT finding and cerebrospinal fluid proteins in muscular dystrophy patients

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Hirase, Tsutomu; Ide, Masami; Araki, Shukuro; Okamoto, Hiroshi (Kumamoto Univ. (Japan). School of Medicine); Kawasaki, Shoichiro; Imamura, Shigehiro

1983-06-01

We analyzed the microcomponents of protein fractions in the cerebrospinal fluid of patients with various types of muscular dystrophy. The degenerative pattern is characterized by an increase in the prealbumin and a decrease in the ..gamma..-globulin fraction is shown in the Duchenne and congenital muscular dystrophy. The increase in CSF IgG, ..gamma..-globulin fraction is shown in the myotonic dystrophy. In addition to the abnormality of IQ, EEG, and brain CT, abnormal CSF proteins obviously suggest the presence of CNS involvement in muscular dystrophy.

CT finding and cerebrospinal fluid proteins in muscular dystrophy patients

International Nuclear Information System (INIS)

Hirase, Tsutomu; Ide, Masami; Araki, Shukuro; Okamoto, Hiroshi; Kawasaki, Shoichiro; Imamura, Shigehiro.

1983-01-01

We analyzed the microcomponents of protein fractions in the cerebrospinal fluid of patients with various types of muscular dystrophy. The degenerative pattern is characterized by an increase in the prealbumin and a decrease in the γ-globulin fraction is shown in the Duchenne and congenital muscular dystrophy. The increase in CSF IgG, γ-globulin fraction is shown in the myotonic dystrophy. In addition to the abnormality of IQ, EEG, and brain CT, abnormal CSF proteins obviously suggest the presence of CNS involvement in muscular dystrophy. (author)

Tibialis anterior muscle needle biopsy and sensitive biomolecular methods: a useful tool in myotonic dystrophy type 1

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S. Iachettini

2015-10-01

Full Text Available Myotonic dystrophy type 1 (DM1 is a neuromuscular disorder caused by a CTG repeat expansion in 3’UTR of DMPK gene. This mutation causes accumulation of toxic RNA in nuclear foci leading to splicing misregulation of specific genes. In view of future clinical trials with antisense oligonucleotides in DM1 patients, it is important to set up sensitive and minimally-invasive tools to monitor the efficacy of treatments on skeletal muscle. A tibialis anterior (TA muscle sample of about 60 mg was obtained from 5 DM1 patients and 5 healthy subjects through a needle biopsy. A fragment of about 40 mg was used for histological examination and a fragment of about 20 mg was used for biomolecular analysis. The TA fragments obtained with the minimally-invasive needle biopsy technique is enough to perform all the histopathological and biomolecular evaluations useful to monitor a clinical trial on DM1 patients.

Anterior temporal white matter lesions in myotonic dystrophy with intellectual impairment: an MRI and neuropathological study

International Nuclear Information System (INIS)

Ogata, A.; Tashiro, K.; Terae, S.; Fujita, M.

1998-01-01

We studied 12 patients with myotonic dystrophy using MRI and the Mini-mental state examination (MMSE), to see it specific MRI findings were associated with intellectual impairment. We also compared them with the neuropathological findings in an autopsy case of MD with intellectual impairment. Mild intellectual impairment was found in 8 of the 12 patients. On T 2-weighted and proton density-weighted images, high-intensity areas were seen in cerebral white matter in 10 of the 12 patients. In seven of these, anterior temporal white-matter lesions (ATWML) were found; all seven had mild intellectual impairment (MMSE 22-26), whereas none of the four patients with normal mentation had ATWML. In only one of the eight patients with intellectual impairment were white-matter lesions not found. Pathological findings were severe loss and disordered arrangement of myelin sheaths and axons in addition to heterotopic neurons within anterior temporal white matter. Bilateral ATWML might be a factor for intellectual impairment in MD. The retrospective pathological study raised the possibility that the ATWML are compatible with focal dysplasia of white matter. (orig.)

The relative frequency of common neuromuscular diagnoses in a reference center.

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Cotta, Ana; Paim, Júlia Filardi; Carvalho, Elmano; da-Cunha-Júnior, Antonio Lopes; Navarro, Monica M; Valicek, Jaquelin; Menezes, Miriam Melo; Nunes, Simone Vilela; Xavier-Neto, Rafael; Baptista, Sidney; Lima, Luciano Romero; Takata, Reinaldo Issao; Vargas, Antonio Pedro

2017-11-01

The diagnostic procedure in neuromuscular patients is complex. Knowledge of the relative frequency of neuromuscular diseases within the investigated population is important to allow the neurologist to perform the most appropriate diagnostic tests. To report the relative frequency of common neuromuscular diagnoses in a reference center. A 17-year chart review of patients with suspicion of myopathy. Among 3,412 examinations, 1,603 (46.98%) yielded confirmatory results: 782 (48.78%) underwent molecular studies, and 821 (51.21%) had muscle biopsies. The most frequent diagnoses were: dystrophinopathy 460 (28.70%), mitochondriopathy 330 (20.59%), spinal muscular atrophy 158 (9.86%), limb girdle muscular dystrophy 157 (9.79%), Steinert myotonic dystrophy 138 (8.61%), facioscapulohumeral muscular dystrophy 99 (6.17%), and other diagnoses 261 (16.28%). Using the presently-available diagnostic techniques in this service, a specific limb girdle muscular dystrophy subtype diagnosis was reached in 61% of the patients. A neuromuscular-appropriate diagnosis is important for genetic counseling, rehabilitation orientation, and early treatment of respiratory and cardiac complications.

The relative frequency of common neuromuscular diagnoses in a reference center

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Ana Cotta

Full Text Available ABSTRACT The diagnostic procedure in neuromuscular patients is complex. Knowledge of the relative frequency of neuromuscular diseases within the investigated population is important to allow the neurologist to perform the most appropriate diagnostic tests. Objective: To report the relative frequency of common neuromuscular diagnoses in a reference center. Methods: A 17-year chart review of patients with suspicion of myopathy. Results: Among 3,412 examinations, 1,603 (46.98% yielded confirmatory results: 782 (48.78% underwent molecular studies, and 821 (51.21% had muscle biopsies. The most frequent diagnoses were: dystrophinopathy 460 (28.70%, mitochondriopathy 330 (20.59%, spinal muscular atrophy 158 (9.86%, limb girdle muscular dystrophy 157 (9.79%, Steinert myotonic dystrophy 138 (8.61%, facioscapulohumeral muscular dystrophy 99 (6.17%, and other diagnoses 261 (16.28%. Conclusion: Using the presently-available diagnostic techniques in this service, a specific limb girdle muscular dystrophy subtype diagnosis was reached in 61% of the patients. A neuromuscular-appropriate diagnosis is important for genetic counseling, rehabilitation orientation, and early treatment of respiratory and cardiac complications.

Non-Coding RNAs in Muscle Dystrophies

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Alessandra Ferlini

2013-09-01

Full Text Available ncRNAs are the most recently identified class of regulatory RNAs with vital functions in gene expression regulation and cell development. Among the variety of roles they play, their involvement in human diseases has opened new avenues of research towards the discovery and development of novel therapeutic approaches. Important data come from the field of hereditary muscle dystrophies, like Duchenne muscle dystrophy and Myotonic dystrophies, rare diseases affecting 1 in 7000–15,000 newborns and is characterized by severe to mild muscle weakness associated with cardiac involvement. Novel therapeutic approaches are now ongoing for these diseases, also based on splicing modulation. In this review we provide an overview about ncRNAs and their behavior in muscular dystrophy and explore their links with diagnosis, prognosis and treatments, highlighting the role of regulatory RNAs in these pathologies.

Feasibility of Lung Volume Recruitment in Early Neuromuscular Weakness: A Comparison Between Amyotrophic Lateral Sclerosis, Myotonic Dystrophy, and Postpolio Syndrome.

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Kaminska, Marta; Browman, Franceen; Trojan, Daria A; Genge, Angela; Benedetti, Andrea; Petrof, Basil J

2015-07-01

Lung volume recruitment (LVR) is a cough assistance technique used in persons with neuromuscular disorders (NMDs), most typically in those requiring noninvasive ventilation (NIV). Whether it may be useful in persons with NMDs who have milder respiratory impairment is unknown. To assess the feasibility, impact on quality of life (QOL), and preliminary physiological effects of daily LVR in different categories of persons with NMDs who have an early stage of respiratory impairment. Feasibility study. Academic tertiary care center. Outpatients diagnosed with amyotrophic lateral sclerosis (n = 8), postpolio syndrome (n = 10), and myotonic dystrophy (n = 6) who had restrictive respiratory defects but were not yet using NIV. Participants were asked to perform LVR up to 4 times daily and log their LVR use in a diary. Physiological measurements and questionnaires were completed at baseline and after 3 months. Compliance with LVR use was assessed, along with QOL and willingness to continue the treatment. Physiological measurements included forced vital capacity (FVC), lung insufflation capacity (LIC), and the LIC minus FVC difference. Of the 24 recruited subjects, 7 with amyotrophic lateral sclerosis, 7 with postpolio syndrome, and 5 with myotonic dystrophy completed the study (n = 19). At baseline, mean values for FVC and spontaneous peak cough flow were 59.9% predicted and 373.1 L/min, respectively. For subjects completing the study, 74% were willing to continue long-term LVR use, and QOL scores were not adversely affected by LVR in any NMD subgroup. The LIC-FVC difference increased from baseline to follow-up by a mean of 0.243 L (P = .006) in all subjects (n = 19), suggesting a possible improvement in respiratory system mechanics. In patients with NMDs who have early restrictive respiratory defects but do not yet require NIV, regular use of LVR is feasible with no negative impact on QOL over a 3-month period and may have physiological benefits. Further work is needed to

Science.gov (United States)

MEOLA, GIOVANNI

2013-01-01

Myotonic dystrophy (DM) is the most common adult muscular dystrophy, characterized by autosomal dominant progressive myopathy, myotonia and multiorgan involvement. To date two distinct forms caused by similar mutations have been identified. Myotonic dystrophy type 1 (DM1, Steinert's disease) was described more than 100 years ago and is caused by a (CTG)n expansion in DMPK, while myotonic dystrophy type 2 (DM2) was identified only 18 years ago and is caused by a (CCTG)n expansion in ZNF9/CNBP. When transcribed into CUG/CCUG-containing RNA, mutant transcripts aggregate as nuclear foci that sequester RNA-binding proteins, resulting in spliceopathy of downstream effector genes. Despite clinical and genetic similarities, DM1 and DM2 are distinct disorders requiring different diagnostic and management strategies. DM1 may present in four different forms: congenital, early childhood, adult onset and late-onset oligosymptomatic DM1. Congenital DM1 is the most severe form of DM characterized by extreme muscle weakness and mental retardation. In DM2 the clinical phenotype is extremely variable and there are no distinct clinical subgroups. Congenital and childhood-onset forms are not present in DM2 and, in contrast to DM1, myotonia may be absent even on EMG. Due to the lack of awareness of the disease among clinicians, DM2 remains largely underdiagnosed. The delay in receiving the correct diagnosis after onset of first symptoms is very long in DM: on average more than 5 years for DM1 and more than 14 years for DM2 patients. The long delay in the diagnosis of DM causes unnecessary problems for the patients to manage their lives and anguish with uncertainty of prognosis and treatment. PMID:24803843

Downregulation of the Glial GLT1 Glutamate Transporter and Purkinje Cell Dysfunction in a Mouse Model of Myotonic Dystrophy

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Géraldine Sicot

2017-06-01

Full Text Available Brain function is compromised in myotonic dystrophy type 1 (DM1, but the underlying mechanisms are not fully understood. To gain insight into the cellular and molecular pathways primarily affected, we studied a mouse model of DM1 and brains of adult patients. We found pronounced RNA toxicity in the Bergmann glia of the cerebellum, in association with abnormal Purkinje cell firing and fine motor incoordination in DM1 mice. A global proteomics approach revealed downregulation of the GLT1 glutamate transporter in DM1 mice and human patients, which we found to be the result of MBNL1 inactivation. GLT1 downregulation in DM1 astrocytes increases glutamate neurotoxicity and is detrimental to neurons. Finally, we demonstrated that the upregulation of GLT1 corrected Purkinje cell firing and motor incoordination in DM1 mice. Our findings show that glial defects are critical in DM1 brain pathophysiology and open promising therapeutic perspectives through the modulation of glutamate levels.

Genome wide identification of aberrant alternative splicing events in myotonic dystrophy type 2.

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Perfetti, Alessandra; Greco, Simona; Fasanaro, Pasquale; Bugiardini, Enrico; Cardani, Rosanna; Garcia-Manteiga, Jose M; Manteiga, Jose M Garcia; Riba, Michela; Cittaro, Davide; Stupka, Elia; Meola, Giovanni; Martelli, Fabio

2014-01-01

Myotonic dystrophy type 2 (DM2) is a genetic, autosomal dominant disease due to expansion of tetraplet (CCTG) repetitions in the first intron of the ZNF9/CNBP gene. DM2 is a multisystemic disorder affecting the skeletal muscle, the heart, the eye and the endocrine system. According to the proposed pathological mechanism, the expanded tetraplets have an RNA toxic effect, disrupting the splicing of many mRNAs. Thus, the identification of aberrantly spliced transcripts is instrumental for our understanding of the molecular mechanisms underpinning the disease. The aim of this study was the identification of new aberrant alternative splicing events in DM2 patients. By genome wide analysis of 10 DM2 patients and 10 controls (CTR), we identified 273 alternative spliced exons in 218 genes. While many aberrant splicing events were already identified in the past, most were new. A subset of these events was validated by qPCR assays in 19 DM2 and 15 CTR subjects. To gain insight into the molecular pathways involving the identified aberrantly spliced genes, we performed a bioinformatics analysis with Ingenuity system. This analysis indicated a deregulation of development, cell survival, metabolism, calcium signaling and contractility. In conclusion, our genome wide analysis provided a database of aberrant splicing events in the skeletal muscle of DM2 patients. The affected genes are involved in numerous pathways and networks important for muscle physio-pathology, suggesting that the identified variants may contribute to DM2 pathogenesis.

Targeting deregulated AMPK/mTORC1 pathways improves muscle function in myotonic dystrophy type I.

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Brockhoff, Marielle; Rion, Nathalie; Chojnowska, Kathrin; Wiktorowicz, Tatiana; Eickhorst, Christopher; Erne, Beat; Frank, Stephan; Angelini, Corrado; Furling, Denis; Rüegg, Markus A; Sinnreich, Michael; Castets, Perrine

2017-02-01

Myotonic dystrophy type I (DM1) is a disabling multisystemic disease that predominantly affects skeletal muscle. It is caused by expanded CTG repeats in the 3'-UTR of the dystrophia myotonica protein kinase (DMPK) gene. RNA hairpins formed by elongated DMPK transcripts sequester RNA-binding proteins, leading to mis-splicing of numerous pre-mRNAs. Here, we have investigated whether DM1-associated muscle pathology is related to deregulation of central metabolic pathways, which may identify potential therapeutic targets for the disease. In a well-characterized mouse model for DM1 (HSALR mice), activation of AMPK signaling in muscle was impaired under starved conditions, while mTORC1 signaling remained active. In parallel, autophagic flux was perturbed in HSALR muscle and in cultured human DM1 myotubes. Pharmacological approaches targeting AMPK/mTORC1 signaling greatly ameliorated muscle function in HSALR mice. AICAR, an AMPK activator, led to a strong reduction of myotonia, which was accompanied by partial correction of misregulated alternative splicing. Rapamycin, an mTORC1 inhibitor, improved muscle relaxation and increased muscle force in HSALR mice without affecting splicing. These findings highlight the involvement of AMPK/mTORC1 deregulation in DM1 muscle pathophysiology and may open potential avenues for the treatment of this disease.

CT findings of muscular dystrophy

International Nuclear Information System (INIS)

Saitoh, Hiroshi

1991-01-01

CT scans of muscles in patients with limb girdle type (LG), myotonic type (MYD) and Duchenne type (DMD) dystrophies were obtained at five different body levels: the neck, L3 vertebral body, pelvic girdle, thigh and lower leg. CT numbers, cross sectional areas (CSA) and %CSA of muscle or fat were evaluated in each muscle. The characteristic CT patterns for each type of muscular dystrophy were obtained. Compared with DMD, the gracilis and soleus were more severely damaged in LG and the biceps femoris remained relatively preserved among the hamstrings. In addition, the multifidus of the neck and sternocleidomastoid also were more severely damaged in MYD. This study suggests that CT scan will be useful in the differential diagnosis of these types of muscular dystrophy as well as in planning appropriate rehabilitation and detecting damaged muscles. (author)

Uncovering the Role of Hypermethylation by CTG Expansion in Myotonic Dystrophy Type 1 Using Mutant Human Embryonic Stem Cells

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Yanovsky-Dagan, Shira; Avitzour, Michal; Altarescu, Gheona; Renbaum, Paul; Eldar-Geva, Talia; Schonberger, Oshrat; Mitrani-Rosenbaum, Stella; Levy-Lahad, Ephrat; Birnbaum, Ramon Y.; Gepstein, Lior; Epsztejn-Litman, Silvina; Eiges, Rachel

2015-01-01

Summary CTG repeat expansion in DMPK, the cause of myotonic dystrophy type 1 (DM1), frequently results in hypermethylation and reduced SIX5 expression. The contribution of hypermethylation to disease pathogenesis and the precise mechanism by which SIX5 expression is reduced are unknown. Using 14 different DM1-affected human embryonic stem cell (hESC) lines, we characterized a differentially methylated region (DMR) near the CTGs. This DMR undergoes hypermethylation as a function of expansion size in a way that is specific to undifferentiated cells and is associated with reduced SIX5 expression. Using functional assays, we provide evidence for regulatory activity of the DMR, which is lost by hypermethylation and may contribute to DM1 pathogenesis by causing SIX5 haplo-insufficiency. This study highlights the power of hESCs in disease modeling and describes a DMR that functions both as an exon coding sequence and as a regulatory element whose activity is epigenetically hampered by a heritable mutation. PMID:26190529

Uncovering the Role of Hypermethylation by CTG Expansion in Myotonic Dystrophy Type 1 Using Mutant Human Embryonic Stem Cells

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Shira Yanovsky-Dagan

2015-08-01

Full Text Available CTG repeat expansion in DMPK, the cause of myotonic dystrophy type 1 (DM1, frequently results in hypermethylation and reduced SIX5 expression. The contribution of hypermethylation to disease pathogenesis and the precise mechanism by which SIX5 expression is reduced are unknown. Using 14 different DM1-affected human embryonic stem cell (hESC lines, we characterized a differentially methylated region (DMR near the CTGs. This DMR undergoes hypermethylation as a function of expansion size in a way that is specific to undifferentiated cells and is associated with reduced SIX5 expression. Using functional assays, we provide evidence for regulatory activity of the DMR, which is lost by hypermethylation and may contribute to DM1 pathogenesis by causing SIX5 haplo-insufficiency. This study highlights the power of hESCs in disease modeling and describes a DMR that functions both as an exon coding sequence and as a regulatory element whose activity is epigenetically hampered by a heritable mutation.

Creatine monohydrate supplementation does not increase muscle strength, lean body mass, or muscle phosphocreatine in patients with myotonic dystrophy type 1.

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Tarnopolsky, Mark; Mahoney, Douglas; Thompson, Terry; Naylor, Heather; Doherty, Timothy J

2004-01-01

Creatine monohydrate (CrM) supplementation may increase strength in some types of muscular dystrophy. A recent study in myotonic muscular dystrophy type 1 (DM1) did not find a significant treatment effect, but measurements of muscle phosphocreatine (PCr) were not performed. We completed a randomized, double-blind, cross-over trial using 34 genetically confirmed adult DM1 patients without significant cognitive impairment. Participants received CrM (5 g, approximately 0.074 g/kg daily) and a placebo for each 4-month phase with a 6-week wash-out. Spirometry, manual muscle testing, quantitative isometric strength testing of handgrip, foot dorsiflexion, and knee extension, handgrip and foot dorsiflexion endurance, functional tasks, activity of daily living scales, body composition (total, bone, and fat-free mass), serum creatine kinase activity, serum creatinine concentration and clearance, and liver function tests were completed before and after each intervention, and muscle PCr/beta-adenosine triphosphate (ATP) ratios of the forearm flexor muscles were completed at the end of each phase. CrM supplementation did not increase any of the outcome measurements except for plasma creatinine concentration (but not creatinine clearance). Thus, CrM supplementation at 5 g daily does not have any effects on muscle strength, body composition, or activities of daily living in patients with DM1, perhaps because of a failure of the supplementation to increase muscle PCr/beta-ATP content.

Circulating Irisin Is Reduced in Male Patients with Type 1 and Type 2 Myotonic Dystrophies

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Elena Dozio

2017-11-01

Full Text Available ContextMyotonic dystrophies (DM are dominantly inherited muscle disorders characterized by myotonia, muscle weakness, and wasting. The reasons for sarcopenia in DMs are uncleared and multiple factors are involved. Irisin, a positive hormone regulator of muscle growth and bone, may play a role.ObjectivesTo investigate (1 circulating irisin in a series of DM1 and DM2 male patients compared with healthy controls and (2 the relationships between irisin and anthropometric, metabolic and hormonal parameters.Design and study participantsThis is a cross-sectional study. Fasting blood samples for glucometabolic, gonadic, bone markers, and irisin were collected from 28 ambulatory DM1, 10 DM2, and 23 age-matched healthy male subjects. Body composition and bone mineralization [bone mineral density (BMD] were measured by DEXA. Echocardiographic assessment and visceral adiposity, namely, liver and epicardial fat, were investigated by ultrasound. Irisin released from cultured myotubes derived from 3 DM1, 3 DM2, and 3 healthy donors was assayed.ResultsPlasma irisin levels were definitely lower in both DM1 and DM2 patients than in controls with no difference between DM1 and DM2. Irisin released from DM1 and DM2 myotubes was similar to that released from myotubes of the non-DM donors, though diabetic DM2 myotubes released more irisin than DM1 myotubes. There was no correlation between irisin and muscle strength or lean mass in both DM1 and DM2 patients. In DM1 patients, plasma irisin levels correlated negatively with oxygen consumption and positively with insulin resistance, while in DM2 patients plasma irisin levels positively correlated with fat mass at arms and legs levels. No correlation with visceral fat, left ventricular mass, and gonadal hormones could be detected. In both DM1 and DM2 patients, legs BMD parameters positively correlated with plasma irisin levels.ConclusionPlasma irisin is reduced in both DM1 and DM2 male patients likely reflecting muscle

Electromechanical delay components during skeletal muscle contraction and relaxation in patients with myotonic dystrophy type 1.

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Esposito, Fabio; Cè, Emiliano; Rampichini, Susanna; Limonta, Eloisa; Venturelli, Massimo; Monti, Elena; Bet, Luciano; Fossati, Barbara; Meola, Giovanni

2016-01-01

The electromechanical delay during muscle contraction and relaxation can be partitioned into mainly electrochemical and mainly mechanical components by an EMG, mechanomyographic, and force combined approach. Component duration and measurement reliability were investigated during contraction and relaxation in a group of patients with myotonic dystrophy type 1 (DM1, n = 13) and in healthy controls (n = 13). EMG, mechanomyogram, and force were recorded in DM1 and in age- and body-matched controls from tibialis anterior (distal muscle) and vastus lateralis (proximal muscle) muscles during maximum voluntary and electrically-evoked isometric contractions. The electrochemical and mechanical components of the electromechanical delay during muscle contraction and relaxation were calculated off-line. Maximum strength was significantly lower in DM1 than in controls under both experimental conditions. All electrochemical and mechanical components were significantly longer in DM1 in both muscles. Measurement reliability was very high in both DM1 and controls. The high reliability of the measurements and the differences between DM1 patients and controls suggest that the EMG, mechanomyographic, and force combined approach could be utilized as a valid tool to assess the level of neuromuscular dysfunction in this pathology, and to follow the efficacy of pharmacological or non-pharmacological interventions. Copyright © 2015 Elsevier B.V. All rights reserved.

Cognition and event-related potentials in adult-onset non-demented myotonic dystrophy type 1.

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Tanaka, H; Arai, M; Harada, M; Hozumi, A; Hirata, K

2012-02-01

To clarify the cognitive and event-related potentials (ERPs) profiles of adult-onset genetically-proven non-demented myotonic dystrophy type 1 (DM1). Fourteen DM1 patients and matched 14 normal controls were enrolled. DM1 patients were compared with normal controls, using a variety of neuropsychological tests; an auditory "oddball" counting paradigm for the ERPs, and low-resolution brain electromagnetic tomography (LORETA). For patients, ERPs and neuropsychological parameters were correlated with CTG repeat size, duration of illness, grip strength, and arterial blood gas analysis. Frontal lobe dysfunction, prolonged N1 latency, and attenuated N2/P3 amplitudes were observed in DM1. Longer CTG repeat size was associated with fewer categories achieved on Wisconsin Card Sorting Test. Greater grip strength was associated with better scores on color-word "interference" of Stroop test. P3 latency was negatively correlated with PaO(2). LORETA revealed significant hypoactivities at the orbitofrontal and medial temporal lobe, cingulate, and insula. There was no correlation between ERPs and CTG expansion. Adult-onset non-demented DM1 presented frontal lobe dysfunction. Absence of correlations between CTG repeat size and objective ERP parameters suggested CTG expansion in lymphocytes does not directly contribute to cognitive dysfunction. CTG expansion in lymphocytes does not directly contribute to cognitive dysfunction of adult-onset non-demented DM1. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Structural and functional cardiac changes in myotonic dystrophy type 1: a cardiovascular magnetic resonance study

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Hermans Mieke CE

2012-07-01

Full Text Available Abstract Background Myotonic dystrophy type 1 (MD1 is a neuromuscular disorder with potential involvement of the heart and increased risk of sudden death. Considering the importance of cardiomyopathy as a predictor of prognosis, we aimed to systematically evaluate and describe structural and functional cardiac alterations in patients with MD1. Methods Eighty MD1 patients underwent physical examination, electrocardiography (ECG, echocardiography and cardiovascular magnetic resonance (CMR. Blood samples were taken for determination of NT-proBNP plasma levels and CTG repeat length. Results Functional and structural abnormalities were detected in 35 patients (44%. Left ventricular systolic dysfunction was found in 20 cases, left ventricular dilatation in 7 patients, and left ventricular hypertrophy in 6 patients. Myocardial fibrosis was seen in 10 patients (12.5%. In general, patients had low left ventricular mass indexes. Right ventricular involvement was uncommon and only seen together with left ventricular abnormalities. Functional or structural cardiac involvement was associated with age (p = 0.04, male gender (p Conclusions CMR can be useful to detect early structural and functional myocardial abnormalities in patients with MD1. Myocardial involvement is strongly associated with conduction abnormalities, but a normal ECG does not exclude myocardial alterations. These findings lend support to the hypothesis that MD1 patients have a complex cardiac phenotype, including both myocardial and conduction system alteration.

Participation restriction in childhood phenotype of myotonic dystrophy type 1: a systematic retrospective chart review.

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Gagnon, Cynthia; Kierkegaard, Marie; Blackburn, Catherine; Chrestian, Nicolas; Lavoie, Mélissa; Bouchard, Marie-Frédéric; Mathieu, Jean

2017-03-01

Myotonic dystrophy type 1 (DM1), a neuromuscular disorder, is divided into four clinical phenotypes: congenital; childhood; adult-onset, and late-onset. Publications about the childhood phenotype, especially the long-term outcome, are scarce. The aims of this study were to assess and describe participation outcomes in adults with the childhood phenotype. A retrospective chart methodology. Data were extracted from health records for 63 adults with childhood DM1 (32 males, 31 females; mean age 34y, standard deviation [SD] 11y 6mo; range 18-54y) who had attended the Saguenay Neuromuscular Clinic, Canada. Thirty-four adults (54%) lived with their parents or in foster homes, and most patients needed services or help to live independently. A significant proportion (22%) were isolated in regard to friendship. Very few adults had children, although 33% lived with a spouse. The majority of patients (86%) relied on social security and only one person was currently working. Financial responsibilities were often an issue and 13 (21%) were under legal guardianship. This study showed that patients with the childhood phenotype present a guarded prognosis regarding long-term social participation. These participation restrictions could be related to behavioural, cognitive, and social stigma problems in childhood. This study illustrates the absolute necessity to pursue an interdisciplinary follow-up of these patients when they are reaching adulthood. © 2016 Mac Keith Press.

Uncovering the Role of Hypermethylation by CTG Expansion in Myotonic Dystrophy Type 1 Using Mutant Human Embryonic Stem Cells.

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Yanovsky-Dagan, Shira; Avitzour, Michal; Altarescu, Gheona; Renbaum, Paul; Eldar-Geva, Talia; Schonberger, Oshrat; Mitrani-Rosenbaum, Stella; Levy-Lahad, Ephrat; Birnbaum, Ramon Y; Gepstein, Lior; Epsztejn-Litman, Silvina; Eiges, Rachel

2015-08-11

CTG repeat expansion in DMPK, the cause of myotonic dystrophy type 1 (DM1), frequently results in hypermethylation and reduced SIX5 expression. The contribution of hypermethylation to disease pathogenesis and the precise mechanism by which SIX5 expression is reduced are unknown. Using 14 different DM1-affected human embryonic stem cell (hESC) lines, we characterized a differentially methylated region (DMR) near the CTGs. This DMR undergoes hypermethylation as a function of expansion size in a way that is specific to undifferentiated cells and is associated with reduced SIX5 expression. Using functional assays, we provide evidence for regulatory activity of the DMR, which is lost by hypermethylation and may contribute to DM1 pathogenesis by causing SIX5 haplo-insufficiency. This study highlights the power of hESCs in disease modeling and describes a DMR that functions both as an exon coding sequence and as a regulatory element whose activity is epigenetically hampered by a heritable mutation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Intellectual impairment and brain MRI findings in myotonic dystrophy. With a special reference to hippocampal atrophy and white matter lesions

International Nuclear Information System (INIS)

Kato, Etsuko; Takahashi, Satoshi; Yonezawa, Hisashi

1995-01-01

We performed a correlative study between intellectual impairment, CTG repeat expansion and magnetic resonance imaging (MRI) abnormalities, including hippocampal atrophy, white matter lesions and ventricular dilatation in 15 patients with myotonic dystrophy (MD). They included 4 males and 11 females aged from 20 to 66 years, averaging 43 years of age and 15 years of duration of illness. Nine patients had intellectual impairment (WAIS-R<80). Negative correlations were found between full scale IQ (FSIQ), duration of illness (p<0.05) and CTG repeat expansion (p<0.05). Compared with normal controls, the patients with MD showed a significant reduction in size of the hippocampal head (p<0.01), which was positively correlated to FSIQ, verbal IQ and performance IQ levels (p<0.05). Ten patients had white matter lesions. Severer white matter lesions tended to be recognized in patients with longer duration of illness and with decreased FSIQ level. These results suggest that hippocampal atrophy and white matter lesions are related to intellectual impairment in patients with MD. (author)

Increased autophagy and apoptosis contribute to muscle atrophy in a myotonic dystrophy type 1 Drosophila model

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Ariadna Bargiela

2015-07-01

Full Text Available Muscle mass wasting is one of the most debilitating symptoms of myotonic dystrophy type 1 (DM1 disease, ultimately leading to immobility, respiratory defects, dysarthria, dysphagia and death in advanced stages of the disease. In order to study the molecular mechanisms leading to the degenerative loss of adult muscle tissue in DM1, we generated an inducible Drosophila model of expanded CTG trinucleotide repeat toxicity that resembles an adult-onset form of the disease. Heat-shock induced expression of 480 CUG repeats in adult flies resulted in a reduction in the area of the indirect flight muscles. In these model flies, reduction of muscle area was concomitant with increased apoptosis and autophagy. Inhibition of apoptosis or autophagy mediated by the overexpression of DIAP1, mTOR (also known as Tor or muscleblind, or by RNA interference (RNAi-mediated silencing of autophagy regulatory genes, achieved a rescue of the muscle-loss phenotype. In fact, mTOR overexpression rescued muscle size to a size comparable to that in control flies. These results were validated in skeletal muscle biopsies from DM1 patients in which we found downregulated autophagy and apoptosis repressor genes, and also in DM1 myoblasts where we found increased autophagy. These findings provide new insights into the signaling pathways involved in DM1 disease pathogenesis.

Assessing the influence of age and gender on the phenotype of myotonic dystrophy type 2.

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Montagnese, Federica; Mondello, Stefania; Wenninger, Stephan; Kress, Wolfram; Schoser, Benedikt

2017-12-01

This study aims to provide a detailed clinical characterization of a large cohort of myotonic dystrophy type 2 (DM2) patients investigating the influence of age and gender as modifying factors of DM2 phenotype. A retrospective study was conducted on 307 patients with genetically confirmed DM2. The following data were analyzed: (1) demographics, (2) clinical features (first symptom, muscular complaints, and multisystemic involvement), (3) diagnostics (serological tests, electromyography, and muscle biopsy). In this cohort (186 females, 121 males), a proximal weakness was the leading symptom at onset (55.4%), followed by myalgia (35.5%) and myotonia (25.4%). Proximal weakness was more common in women than men (64.9 vs. 43.8%, p = 0.0006), whereas being male was associated with higher odds for developing myalgia [OR 2.94 (95% CI 1.53-5.67)]. Patients with muscle weakness at onset were older than those with myalgia and myotonia (p women (p = 0.002 and p = 0.002, respectively). Early onset of DM2 is an independent risk factor for the occurrence of multisystemic involvement [OR 0.94 (95% CI 0.90-0.98)]. In this updated clinical description of DM2 emerges a profound gender and age influence on the phenotype, emphasizing that female gender and ageing may be associated with a higher disease burden. These age- and gender-specific differences should be considered in diagnostics, management, and future clinical studies of DM2.

Overweight Is an Independent Risk Factor for Reduced Lung Volumes in Myotonic Dystrophy Type 1.

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Charlotte G W Seijger

Full Text Available In this large observational study population of 105 myotonic dystrophy type 1 (DM1 patients, we investigate whether bodyweight is a contributor of total lung capacity (TLC independent of the impaired inspiratory muscle strength.Body composition was assessed using the combination of body mass index (BMI and fat-free mass index. Pulmonary function tests and respiratory muscle strength measurements were performed on the same day. Patients were stratified into normal (BMI < 25 kg/m(2 and overweight (BMI ≥ 25 kg/m(2 groups. Multiple linear regression was used to find significant contributors for TLC.Overweight was present in 59% of patients, and body composition was abnormal in almost all patients. In overweight patients, TLC was significantly (p = 2.40×10(-3 decreased, compared with normal-weight patients, while inspiratory muscle strength was similar in both groups. The decrease in TLC in overweight patients was mainly due to a decrease in expiratory reserve volume (ERV further illustrated by a highly significant (p = 1.33×10(-10 correlation between BMI and ERV. Multiple linear regression showed that TLC can be predicted using only BMI and the forced inspiratory volume in 1 second, as these were the only significant contributors.This study shows that, in DM1 patients, overweight further reduces lung volumes, as does impaired inspiratory muscle strength. Additionally, body composition is abnormal in almost all DM1 patients.

Muscular Dystrophies at Different Ages: Metabolic and Endocrine Alterations

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Oriana del Rocío Cruz Guzmán

2012-01-01

Full Text Available Common metabolic and endocrine alterations exist across a wide range of muscular dystrophies. Skeletal muscle plays an important role in glucose metabolism and is a major participant in different signaling pathways. Therefore, its damage may lead to different metabolic disruptions. Two of the most important metabolic alterations in muscular dystrophies may be insulin resistance and obesity. However, only insulin resistance has been demonstrated in myotonic dystrophy. In addition, endocrine disturbances such as hypogonadism, low levels of testosterone, and growth hormone have been reported. This eventually will result in consequences such as growth failure and delayed puberty in the case of childhood dystrophies. Other consequences may be reduced male fertility, reduced spermatogenesis, and oligospermia, both in childhood as well as in adult muscular dystrophies. These facts all suggest that there is a need for better comprehension of metabolic and endocrine implications for muscular dystrophies with the purpose of developing improved clinical treatments and/or improvements in the quality of life of patients with dystrophy. Therefore, the aim of this paper is to describe the current knowledge about of metabolic and endocrine alterations in diverse types of dystrophinopathies, which will be divided into two groups: childhood and adult dystrophies which have different age of onset.

Pentamidine rescues contractility and rhythmicity in a Drosophila model of myotonic dystrophy heart dysfunction

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Mouli Chakraborty

2015-12-01

Full Text Available Up to 80% of individuals with myotonic dystrophy type 1 (DM1 will develop cardiac abnormalities at some point during the progression of their disease, the most common of which is heart blockage of varying degrees. Such blockage is characterized by conduction defects and supraventricular and ventricular tachycardia, and carries a high risk of sudden cardiac death. Despite its importance, very few animal model studies have focused on the heart dysfunction in DM1. Here, we describe the characterization of the heart phenotype in a Drosophila model expressing pure expanded CUG repeats under the control of the cardiomyocyte-specific driver GMH5-Gal4. Morphologically, expression of 250 CUG repeats caused abnormalities in the parallel alignment of the spiral myofibrils in dissected fly hearts, as revealed by phalloidin staining. Moreover, combined immunofluorescence and in situ hybridization of Muscleblind and CUG repeats, respectively, confirmed detectable ribonuclear foci and Muscleblind sequestration, characteristic features of DM1, exclusively in flies expressing the expanded CTG repeats. Similarly to what has been reported in humans with DM1, heart-specific expression of toxic RNA resulted in reduced survival, increased arrhythmia, altered diastolic and systolic function, reduced heart tube diameters and reduced contractility in the model flies. As a proof of concept that the fly heart model can be used for in vivo testing of promising therapeutic compounds, we fed flies with pentamidine, a compound previously described to improve DM1 phenotypes. Pentamidine not only released Muscleblind from the CUG RNA repeats and reduced ribonuclear formation in the Drosophila heart, but also rescued heart arrhythmicity and contractility, and improved fly survival in animals expressing 250 CUG repeats.

Genome Therapy of Myotonic Dystrophy Type 1 iPS Cells for Development of Autologous Stem Cell Therapy.

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Gao, Yuanzheng; Guo, Xiuming; Santostefano, Katherine; Wang, Yanlin; Reid, Tammy; Zeng, Desmond; Terada, Naohiro; Ashizawa, Tetsuo; Xia, Guangbin

2016-08-01

Myotonic dystrophy type 1 (DM1) is caused by expanded Cytosine-Thymine-Guanine (CTG) repeats in the 3'-untranslated region (3' UTR) of the Dystrophia myotonica protein kinase (DMPK) gene, for which there is no effective therapy. The objective of this study is to develop genome therapy in human DM1 induced pluripotent stem (iPS) cells to eliminate mutant transcripts and reverse the phenotypes for developing autologous stem cell therapy. The general approach involves targeted insertion of polyA signals (PASs) upstream of DMPK CTG repeats, which will lead to premature termination of transcription and elimination of toxic mutant transcripts. Insertion of PASs was mediated by homologous recombination triggered by site-specific transcription activator-like effector nuclease (TALEN)-induced double-strand break. We found genome-treated DM1 iPS cells continue to maintain pluripotency. The insertion of PASs led to elimination of mutant transcripts and complete disappearance of nuclear RNA foci and reversal of aberrant splicing in linear-differentiated neural stem cells, cardiomyocytes, and teratoma tissues. In conclusion, genome therapy by insertion of PASs upstream of the expanded DMPK CTG repeats prevented the production of toxic mutant transcripts and reversal of phenotypes in DM1 iPS cells and their progeny. These genetically-treated iPS cells will have broad clinical application in developing autologous stem cell therapy for DM1.

Myotonic Dystrophy and Huntington's Disease Care: "We Like to Think We're Making a Difference".

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LaDonna, Kori A; Watling, Christopher J; Ray, Susan L; Piechowicz, Christine; Venance, Shannon L

2016-09-01

Patient-centered care for individuals with myotonic dystrophy (DM1) and Huntington's disease (HD)-chronic, progressive, and life-limiting neurological conditions-may be challenged by patients' cognitive and behavioral impairments. However, no research has explored health care providers' (HCPs') perspectives about patient-centered care provision for these patients along their disease trajectory. Constructivist grounded theory informed the iterative data collection and analysis process. Eleven DM1 or HD HCPs participated in semistructured interviews, and three stages of coding were used to analyze their interview transcripts. Codes were collapsed into themes and categories. Three categories including an evolving care approach, fluid roles, and making a difference were identified. Participants described that their clinical care approach evolved depending on the patient's disease stage and caregivers' degree of involvement. HCPs described that their main goal was to provide hope to patients and caregivers through medical management, crisis prevention, support, and advocacy. Despite the lack of curative treatments, HCPs perceived that patients benefited from ongoing clinical care provided by proactive clinicians. Providing care for individuals with DM1 and HD is a balancing act. HCPs must strike a balance between (1) the frustrations and rewards of patient-centered care provision, (2) addressing symptoms and preventing and managing crises while focusing on patients' and caregivers' quality of life concerns, and (3) advocating for patients while addressing caregivers' needs. This raises important questions: Is patient-centered care possible for patients with cognitive decline? Does chronic neurological care need to evolve to better address patients' and caregivers' complex needs?

Cognitive decline over time in adults with myotonic dystrophy type 1: A 9-year longitudinal study.

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Gallais, Benjamin; Gagnon, Cynthia; Mathieu, Jean; Richer, Louis

2017-01-01

Myotonic dystrophy type 1 (DM1) is an inherited neuromuscular disease with multisystemic involvement including the central nervous system. The evolution of the cognitive profile is a matter of debate, whether an eventual decline could be global or process-specific. Study aims are to describe, compare and document the clinical relevance of the progression of cognitive abilities in DM1 patients with adult and late-onset phenotypes. A total of 115 DM1 patients (90 adult; 25 late-onset) were assessed twice within a 9-year period on cognitive abilities (language, memory, visual attention, processing speed, visuoconstructive abilities and executive functions) and intellectual functioning (WAIS-R 7). A significant worsening over time was observed for verbal memory, visual attention, and processing speed. The progression in cognitive scores correlated with age and disease duration, but not with nCTG, muscular impairment nor education at baseline. Intellectual functioning remained stable. The rate of decline was higher among the late-onset phenotype than in the adult phenotype. Results showed that executive functions, language, and visual memory are impaired earlier in adult life, while verbal memory, visual attention, and processing speed decline later. Globally, results suggest an early and accelerated normal ageing process. This longitudinal study was based on the largest sample and the longest time period studied to date. These findings are highly relevant for clinical practice and genetic counselling. Copyright © 2016 Elsevier B.V. All rights reserved.

Modelling the pathogenesis of Myotonic Dystrophy type 1 cardiac phenotype through human iPSC-derived cardiomyocytes.

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Spitalieri, Paola; Talarico, Rosa V; Caioli, Silvia; Murdocca, Michela; Serafino, Annalucia; Girasole, Marco; Dinarelli, Simone; Longo, Giovanni; Pucci, Sabina; Botta, Annalisa; Novelli, Giuseppe; Zona, Cristina; Mango, Ruggiero; Sangiuolo, Federica

2018-03-15

Myotonic Dystrophy type 1 (DM1) is a multisystemic disease, autosomal dominant, caused by a CTG repeat expansion in DMPK gene. We assessed the appropriateness of patient-specific induced pluripotent stem cell-derived cardiomyocytes (CMs) as a model to recapitulate some aspects of the pathogenetic mechanism involving cardiac manifestations in DM1 patients. Once obtained in vitro, CMs have been characterized for their morphology and their functionality. CMs DM1 show intranuclear foci and transcript markers abnormally spliced respect to WT ones, as well as several irregularities in nuclear morphology, probably caused by an unbalanced lamin A/C ratio. Electrophysiological characterization evidences an abnormal profile only in CMs DM1 such that the administration of antiarrythmic drugs to these cells highlights even more the functional defect linked to the disease. Finally, Atomic Force Measurements reveal differences in the biomechanical behaviour of CMs DM1, in terms of frequencies and synchronicity of the beats. Altogether the complex phenotype described in this work, strongly reproduces some aspects of the human DM1 cardiac phenotype. Therefore, the present study provides an in vitro model suggesting novel insights into the mechanisms leading to the development of arrhythmogenesis and dilatative cardiomyopathy to consider when approaching to DM1 patients, especially for the risk assessment of sudden cardiac death (SCD). These data could be also useful in identifying novel biomarkers effective in clinical settings and patient-tailored therapies. Copyright © 2018 Elsevier Ltd. All rights reserved.

Structure and Dynamics of RNA Repeat Expansions That Cause Huntington's Disease and Myotonic Dystrophy Type 1.

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Chen, Jonathan L; VanEtten, Damian M; Fountain, Matthew A; Yildirim, Ilyas; Disney, Matthew D

2017-07-11

RNA repeat expansions cause a host of incurable, genetically defined diseases. The most common class of RNA repeats consists of trinucleotide repeats. These long, repeating transcripts fold into hairpins containing 1 × 1 internal loops that can mediate disease via a variety of mechanism(s) in which RNA is the central player. Two of these disorders are Huntington's disease and myotonic dystrophy type 1, which are caused by r(CAG) and r(CUG) repeats, respectively. We report the structures of two RNA constructs containing three copies of a r(CAG) [r(3×CAG)] or r(CUG) [r(3×CUG)] motif that were modeled with nuclear magnetic resonance spectroscopy and simulated annealing with restrained molecular dynamics. The 1 × 1 internal loops of r(3×CAG) are stabilized by one-hydrogen bond (cis Watson-Crick/Watson-Crick) AA pairs, while those of r(3×CUG) prefer one- or two-hydrogen bond (cis Watson-Crick/Watson-Crick) UU pairs. Assigned chemical shifts for the residues depended on the identity of neighbors or next nearest neighbors. Additional insights into the dynamics of these RNA constructs were gained by molecular dynamics simulations and a discrete path sampling method. Results indicate that the global structures of the RNA are A-form and that the loop regions are dynamic. The results will be useful for understanding the dynamic trajectory of these RNA repeats but also may aid in the development of therapeutics.

Neuromuscular diseases: Diagnosis and management.

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Mary, P; Servais, L; Vialle, R

2018-02-01

Neuromuscular diseases (NMDs) affect the peripheral nervous system, which includes the motor neurons and sensory neurons; the muscle itself; or the neuromuscular junction. Thus, the term NMDs encompasses a vast array of different syndromes. Some of these syndromes are of direct relevance to paediatric orthopaedic surgeons, either because the presenting manifestation is a functional sign (e.g., toe-walking) or deformity (e.g., pes cavus or scoliosis) suggesting a need for orthopaedic attention or because orthopaedic abnormalities requiring treatment develop during the course of a known NMD. The main NMDs relevant to the orthopaedic surgeon are infantile spinal muscular atrophy (a motor neuron disease), peripheral neuropathies (chiefly, Charcot-Marie-Tooth disease), congenital muscular dystrophies, progressive muscular dystrophies, and Steinert myotonic dystrophy (or myotonic dystrophy type 1). Muscle weakness is a symptom shared by all these conditions. The paediatric orthopaedic surgeon must be familiar, not only with the musculoskeletal system, but also with many other domains (particularly respiratory and cardiac function and nutrition) that may interfere with the treatment and require preoperative management. Good knowledge of the natural history of each NMD is essential to ensure optimal timing of the therapeutic interventions, which must be performed under the best possible conditions in these usually frail patients. Timing is particularly crucial for the treatment of spinal deformities due to paraspinal muscle hypotonia during growth: depending on the disease and natural history, the treatment may involve non-operative methods or growing rods, followed by spinal fusion. A multidisciplinary approach is always required. Finally, the survival gains achieved in recent years increasingly require attention to preparing for adult life, to orthopaedic problems requiring treatment before the patient leaves the paediatric environment, and to the transition towards the

Orthopaedic Disorders in Myotonic Dystrophy Type 1: descriptive clinical study of 21 patients

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2013-01-01

Background Myotonic Dystrophy Type 1 (DM1) is the most common form of hereditary myopathy presenting in adults. This autosomal-dominant systemic disorder is caused by a CTG repeat, demonstrating various symptoms. A mild, classic and congenital form can be distinguished. Often the quality of life is reduced by orthopaedic problems, such as muscle weakness, contractures, foot or spinal deformities, which limit patients’ mobility. The aim of our study was to gather information about the orthopaedic impairments in patients with DM1 in order to improve the medical care of patients, affected by this rare disease. Methods A retrospective clinical study was carried out including 21 patients (11 male and 10 female), all diagnosed with DM1 by genetic testing. All patients were seen during our special consultations for neuromuscular diseases, during which patients were interviewed and examined. We also reviewed surgery reports of our hospitalized patients. Results We observed several orthopaedic impairments: spinal deformities (scoliosis, hyperkyphosis, rigid spine), contractures (of the upper extremities and the lower extremities), foot deformities (equinus deformity, club foot, pes cavus, pes planovalgus, pes cavovarus, claw toes) and fractures. Five patients were affected by pulmonary diseases (obstructive airway diseases, restrictive lung dysfunctions). Twelve patients were affected by cardiac disorders (congenital heart defects, valvular heart defects, conduction disturbances, pulmonary hypertension, cardiomyopathy). Our patients received conservative therapy (physiotherapy, logopaedic therapy, ergotherapy) and we prescribed orthopaedic technical devices (orthopaedic custom-made shoes, insoles, lower and upper leg orthoses, wheelchair, Rehab Buggy). We performed surgery for spinal and foot deformities: the scoliosis of one patient was stabilized and seven patients underwent surgery for correction of foot deformities. Conclusions An orthopaedic involvement in DM1

Living with myotonic dystrophy; what can be learned from couples? a qualitative study

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van der Wilt Gert

2011-07-01

Full Text Available Abstract Background Myotonic dystrophy type 1 (MD1 is one of the most prevalent neuromuscular diseases, yet very little is known about how MD1 affects the lives of couples and how they themselves manage individually and together. To better match health care to their problems, concerns and needs, it is important to understand their perspective of living with this hereditary, systemic disease. Methods A qualitative study was carried out with a purposive sample of five middle-aged couples, including three men and two women with MD1 and their partners. Fifteen in-depth interviews with persons with MD1, with their partners and with both of them as a couple took place in the homes of the couples in two cities and three villages in the Netherlands in 2009. Results People with MD1 associate this progressive, neuromuscular condition with decreasing abilities, describing physical, cognitive and psychosocial barriers to everyday activities and social participation. Partners highlighted the increasing care giving burden, giving directions and using reminders to compensate for the lack of initiative and avoidant behaviour due to MD1. Couples portrayed the dilemmas and frustrations of renegotiating roles and responsibilities; stressing the importance of achieving a balance between individual and shared activities. All participants experienced a lack of understanding from relatives, friends, and society, including health care, leading to withdrawal and isolation. Health care was perceived as fragmentary, with specialists focusing on specific aspects of the disease rather than seeking to understand the implications of the systemic disorder on daily life. Conclusions Learning from these couples has resulted in recommendations that challenge the tendency to treat MD1 as a condition with primarily physical impairments. It is vital to listen to couples, to elicit the impact of MD1, as a multisystem disorder that influences every aspect of their life together

Stanford Chronic Disease Self-Management Program in myotonic dystrophy: New opportunities for occupational therapists: Stanford Chronic Disease Self-Management Program dans la dystrophie myotonique : De nouvelles opportunités pour les ergothérapeutes.

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Raymond, Kateri; Levasseur, Mélanie; Chouinard, Maud-Christine; Mathieu, Jean; Gagnon, Cynthia

2016-06-01

Chronic disease self-management is a priority in health care. Personal and environmental barriers for populations with neuromuscular disorders might diminish the efficacy of self-management programs, although they have been shown to be an effective intervention in many populations. Owing to their occupational expertise, occupational therapists might optimize self-management program interventions. This study aimed to adapt the Stanford Chronic Disease Self-Management Program (CDSMP) for people with myotonic dystrophy type 1 (DM1) and assess its acceptability and feasibility in this population. Using an adapted version of the Stanford CDSMP, a descriptive pilot study was conducted with 10 participants (five adults with DM1 and their caregivers). A semi-structured interview and questionnaires were used. The Stanford CDSMP is acceptable and feasible for individuals with DM1. However, improvements are required, such as the involvement of occupational therapists to help foster concrete utilization of self-management strategies into day-to-day tasks using their expertise in enabling occupation. Although adaptations are needed, the Stanford CDSMP remains a relevant intervention with populations requiring the application of self-management strategies. © CAOT 2016.

Characterization of sarcoplasmic reticulum Ca(2+) ATPase pumps in muscle of patients with myotonic dystrophy and with hypothyroid myopathy.

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Guglielmi, V; Oosterhof, A; Voermans, N C; Cardani, R; Molenaar, J P; van Kuppevelt, T H; Meola, G; van Engelen, B G; Tomelleri, G; Vattemi, G

2016-06-01

Sarcoplasmic/endoplasmic reticulum Ca(2+) ATPase (SERCA) pumps play the major role in lowering cytoplasmic calcium concentration in skeletal muscle by catalyzing the ATP-dependent transport of Ca(2+) from the cytosol to the lumen of the sarcoplasmic reticulum (SR). Although SERCA abnormalities have been hypothesized to contribute to the dysregulation of intracellular Ca(2+) homeostasis and signaling in muscle of patients with myotonic dystrophy (DM) and hypothyroid myopathy, the characterization of SERCA pumps remains elusive and their impairment is still unclear. We assessed the activity of SR Ca(2+)-ATPase, expression levels and fiber distribution of SERCA1 and SERCA2, and oligomerization of SERCA1 protein in muscle of patients with DM type 1 and 2, and with hypothyroid myopathy. Our data provide evidence that SR Ca(2+) ATPase activity, protein levels and muscle fiber distribution of total SERCA1 and SERCA2, and SERCA1 oligomerization pattern are similar in patients with both DM1 and DM2, hypothyroid myopathy and in control subjects. We prove that SERCA1b, the neonatal isoform of SERCA1, is expressed at protein level in muscle of patients with DM2 and, in lower amount, of patients with DM1. Our present study demonstrates that SERCA function is not altered in muscle of patients with DM and with hypothyroid myopathy. Copyright © 2016 Elsevier B.V. All rights reserved.

Cardiac Involvement in Myotonic Dystrophy Type 2 Patients With Preserved Ejection Fraction: Detection by Cardiovascular Magnetic Resonance.

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Schmacht, Luisa; Traber, Julius; Grieben, Ulrike; Utz, Wolfgang; Dieringer, Matthias A; Kellman, Peter; Blaszczyk, Edyta; von Knobelsdorff-Brenkenhoff, Florian; Spuler, Simone; Schulz-Menger, Jeanette

2016-07-01

Myotonic dystrophy type 2 (DM2) is a genetic disorder characterized by skeletal muscle symptoms, metabolic changes, and cardiac involvement. Histopathologic alterations of the skeletal muscle include fibrosis and fatty infiltration. The aim of this study was to investigate whether subclinical cardiac involvement in DM2 is already detectable in preserved left ventricular function by cardiovascular magnetic resonance. Twenty-seven patients (mean age, 54±10 years; 20 females) with a genetically confirmed diagnosis of DM2 were compared with 17 healthy age- and sex-matched controls using a 1.5 T magnetic resonance imaging. For myocardial tissue differentiation, T1 and T2 mapping, fat/water-separated imaging, focal fibrosis imaging (late gadolinium enhancement [LGE]), and (1)H magnetic resonance spectroscopy were performed. Extracellular volume fraction was calculated. Conduction abnormalities were diagnosed based on Groh criteria. LGE located subepicardial basal inferolateral was detectable in 22% of the patients. Extracellular volume was increased in this region and in the adjacent medial inferolateral segment (P=0.03 compared with healthy controls). In 21% of patients with DM2, fat deposits were detectable (all women). The control group showed no abnormalities. Myocardial triglycerides were not different in LGE-positive and LGE-negative subjects (P=0.47). Six patients had indicators for conduction disease (60% of LGE-positive patients and 12.5% of LGE-negative patients). In DM2, subclinical myocardial injury was already detectable in preserved left ventricular ejection fraction. Extracellular volume was also increased in regions with no focal fibrosis. Myocardial fibrosis was related to conduction abnormalities. © 2016 American Heart Association, Inc.

Responsiveness of performance-based outcome measures for mobility, balance, muscle strength and manual dexterity in adults with myotonic dystrophy type 1.

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Kierkegaard, Marie; Petitclerc, Émilie; Hébert, Luc J; Mathieu, Jean; Gagnon, Cynthia

2018-02-28

To assess changes and responsiveness in outcome measures of mobility, balance, muscle strength and manual dexterity in adults with myotonic dystrophy type 1. A 9-year longitudinal study conducted with 113 patients. The responsiveness of the Timed Up and Go test, Berg Balance Scale, quantitative muscle testing, grip and pinch-grip strength, and Purdue Pegboard Test was assessed using criterion and construct approaches. Patient-reported perceived changes (worse/stable) in balance, walking, lower-limb weakness, stair-climbing and hand weakness were used as criteria. Predefined hypotheses about expected area under the receiver operating characteristic curves (criterion approach) and correlations between relative changes (construct approach) were explored. The direction and magnitude of median changes in outcome measures corresponded with patient-reported changes. Median changes in the Timed Up and Go test, grip strength, pinch-grip strength and Purdue Pegboard Test did not, in general, exceed known measurement errors. Most criterion (72%) and construct (70%) approach hypotheses were supported. Promising responsiveness was found for outcome measures of mobility, balance and muscle strength. Grip strength and manual dexterity measures showed poorer responsiveness. The performance-based outcome measures captured changes over the 9-year period and responsiveness was promising. Knowledge of measurement errors is needed to interpret the meaning of these longitudinal changes.

Ventricular fibrillation induced by coagulating mode bipolar electrocautery during pacemaker implantation in Myotonic Dystrophy type 1 patient.

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Russo, Vincenzo; Rago, Anna; DI Meo, Federica; Cioppa, Nadia Della; Papa, Andrea Antonio; Russo, Maria Giovanna; Nigro, Gerardo

2014-12-01

The occurrence of ventricular fibrillation, induced by bipolar electrocautery during elective dual chamber pacemaker implantation, is reported in a patient affected by Myotonic Distrophy type 1 with normal left ventricular ejection fraction.

Myotonic dystrophy type 1: role of CCG, CTC and CGG interruptions within DMPK alleles in the pathogenesis and molecular diagnosis.

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Santoro, M; Masciullo, M; Silvestri, G; Novelli, G; Botta, A

2017-10-01

Myotonic dystrophy type 1 (DM1) is a multisystem neuromuscular disease caused by a CTG triplet expansion in the 3'-untranslated region (3'-UTR) of DMPK gene. This CTG array is usually uninterrupted in both healthy and DM1 patients, but recent studies identified pathological variant expansions containing unstable CCG, CTC and CGG interruptions with a prevalence of 3-5% of cases. In this review, we will describe the clinical, molecular and genetic issues related to the occurrence of variant expansions associated with DM1. Indeed, the identification of these complex DMPK alleles leads to practical consequences in DM1 genetic counseling and testing, because these exams can give false negative results. Moreover, DM1 patients carrying interrupted alleles can manifest either additional atypical neurological symptoms or, conversely, mild, late-onset forms. Therefore, the prognosis of the disease in these patients is difficult to determine because of the great uncertainty about the genotype-phenotype correlations. We will discuss the putative effects of the variant DM1 alleles on the pathogenic disease mechanisms, including mitotic and meiotic repeats instability and splicing alteration typical of DM1 tissues. Interruptions within the DMPK expanded alleles could also interfere with the chromatin structure, the transcriptional activity of the DM1 locus and the interaction with RNA CUG-binding proteins. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Distinct neuromuscular phenotypes in myotonic dystrophy types 1 and 2 : a whole body highfield MRI study.

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Kornblum, Cornelia; Lutterbey, Götz; Bogdanow, Manuela; Kesper, Kristina; Schild, Hans; Schröder, Rolf; Wattjes, Mike Peter

2006-06-01

Myotonic Dystrophy Type 1 (DM1) and 2 (DM2) present with distinct though overlapping clinical phenotypes. Comparative imaging data on skeletal muscle involvement are not at present available. We used the novel technique of whole body 3.0 Tesla (T) Magnetic Resonance Imaging (MRI) to further characterize musculoskeletal features in DM2 and compared the results with DM1.MRI findings of 15 DM1 and 14 DM2 patients were evaluated with respect to patterns of skeletal muscle affection and clinical data using the Muscular Impairment Rating Scale (MIRS) and Medical Research Council scale (MRC). All DM1 patients had pathological MRI compared with only 5 DM2 patients. In contrast to DM2, DM1 patients showed a characteristic distribution of muscle involvement with frequent and early degeneration of the medial heads of gastrocnemius muscles, and a perifemoral semilunar pattern of quadriceps muscle affection sparing the rectus femoris. The most frequently affected muscles in DM1 were the medial heads of gastrocnemius, soleus, and vastus medialis muscles. In DM2, however, the erector spinae and gluteus maximus muscles were most vulnerable to degeneration. MRI data were in line with the clinical grading in 12 DM1 and 3 DM2 patients. In 3 DM1 and 5 DM2 patients, MRI detected subclinical muscle involvement. 9 DM2 patients with mild to moderate proximal muscle weakness and/or myalgias had normal MRI. Pathological MRI changes in DM2 emerged with increasing age and were restricted to women. Whole body 3.0T MRI is a sensitive imaging technique that demonstrated a characteristic skeletal muscle affection in DM1. In contrast, MRI was no reliable indicator for skeletal muscle involvement in mildly affected DM2 patients since myalgia and mild paresis were usually not reflected by MRI signal alterations.

Muscleblind, BSF and TBPH are mislocalized in the muscle sarcomere of a Drosophila myotonic dystrophy model

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Beatriz Llamusi

2013-01-01

Myotonic dystrophy type 1 (DM1 is a genetic disease caused by the pathological expansion of a CTG trinucleotide repeat in the 3′ UTR of the DMPK gene. In the DMPK transcripts, the CUG expansions sequester RNA-binding proteins into nuclear foci, including transcription factors and alternative splicing regulators such as MBNL1. MBNL1 sequestration has been associated with key features of DM1. However, the basis behind a number of molecular and histological alterations in DM1 remain unclear. To help identify new pathogenic components of the disease, we carried out a genetic screen using a Drosophila model of DM1 that expresses 480 interrupted CTG repeats, i(CTG480, and a collection of 1215 transgenic RNA interference (RNAi fly lines. Of the 34 modifiers identified, two RNA-binding proteins, TBPH (homolog of human TAR DNA-binding protein 43 or TDP-43 and BSF (Bicoid stability factor; homolog of human LRPPRC, were of particular interest. These factors modified i(CTG480 phenotypes in the fly eye and wing, and TBPH silencing also suppressed CTG-induced defects in the flight muscles. In Drosophila flight muscle, TBPH, BSF and the fly ortholog of MBNL1, Muscleblind (Mbl, were detected in sarcomeric bands. Expression of i(CTG480 resulted in changes in the sarcomeric patterns of these proteins, which could be restored by coexpression with human MBNL1. Epistasis studies showed that Mbl silencing was sufficient to induce a subcellular redistribution of TBPH and BSF proteins in the muscle, which mimicked the effect of i(CTG480 expression. These results provide the first description of TBPH and BSF as targets of Mbl-mediated CTG toxicity, and they suggest an important role of these proteins in DM1 muscle pathology.

Three novel serum biomarkers, miR-1, miR-133a, and miR-206 for Limb-girdle muscular dystrophy, Facioscapulohumeral muscular dystrophy, and Becker muscular dystrophy.

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Matsuzaka, Yasunari; Kishi, Soichiro; Aoki, Yoshitsugu; Komaki, Hirofumi; Oya, Yasushi; Takeda, Shin-Ichi; Hashido, Kazuo

2014-11-01

Muscular dystrophies are a clinically and genetically heterogeneous group of inherited myogenic disorders. In clinical tests for these diseases, creatine kinase (CK) is generally used as diagnostic blood-based biomarker. However, because CK levels can be altered by various other factors, such as vigorous exercise, etc., false positive is observed. Therefore, three microRNAs (miRNAs), miR-1, miR-133a, and miR-206, were previously reported as alternative biomarkers for duchenne muscular dystrophy (DMD). However, no alternative biomarkers have been established for the other muscular dystrophies. We, therefore, evaluated whether these miR-1, miR-133a, and miR-206 can be used as powerful biomarkers using the serum from muscular dystrophy patients including DMD, myotonic dystrophy 1 (DM1), limb-girdle muscular dystrophy (LGMD), facioscapulohumeral muscular dystrophy (FSHD), becker muscular dystrophy (BMD), and distal myopathy with rimmed vacuoles (DMRV) by qualitative polymerase chain reaction (PCR) amplification assay. Statistical analysis indicated that all these miRNA levels in serum represented no significant differences between all muscle disorders examined in this study and controls by Bonferroni correction. However, some of these indicated significant differences without correction for testing multiple diseases (P < 0.05). The median values of miR-1 levels in the serum of patients with LGMD, FSHD, and BMD were approximately 5.5, 3.3 and 1.7 compared to that in controls, 0.68, respectively. Similarly, those of miR-133a and miR-206 levels in the serum of BMD patients were about 2.5 and 2.1 compared to those in controls, 1.03 and 1.32, respectively. Taken together, our data demonstrate that levels of miR-1, miR-133a, and miR-206 in serum of BMD and miR-1 in sera of LGMD and FSHD patients showed no significant differences compared with those of controls by Bonferroni correction. However, the results might need increase in sample sizes to evaluate these three miRNAs as

The Myotonic Plot Thickens: Electrical Myotonia in Antimuscle-Specific Kinase Myasthenia Gravis

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Marcus Magnussen

2015-01-01

Full Text Available Electrical myotonia is known to occur in a number of inherited and acquired disorders including myotonic dystrophies, channelopathies, and metabolic, toxic, and inflammatory myopathies. Yet, electrical myotonia in myasthenia gravis associated with antibodies against muscle-specific tyrosine kinase (MuSK has not been previously reported. We describe two such patients, both of whom had a typical presentation of proximal muscle weakness with respiratory failure in the context of a significant electrodecrement in repetitive nerve stimulation. In both cases, concentric needle examination revealed electrical myotonia combined with myopathic motor unit morphology and early recruitment. These findings suggest that MuSK myasthenia should be included within the differential diagnosis of disorders with electrical myotonia.

Functional and histopathological identification of the respiratory failure in a DMSXL transgenic mouse model of myotonic dystrophy

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Petrica-Adrian Panaite

2013-05-01

Acute and chronic respiratory failure is one of the major and potentially life-threatening features in individuals with myotonic dystrophy type 1 (DM1. Despite several clinical demonstrations showing respiratory problems in DM1 patients, the mechanisms are still not completely understood. This study was designed to investigate whether the DMSXL transgenic mouse model for DM1 exhibits respiratory disorders and, if so, to identify the pathological changes underlying these respiratory problems. Using pressure plethysmography, we assessed the breathing function in control mice and DMSXL mice generated after large expansions of the CTG repeat in successive generations of DM1 transgenic mice. Statistical analysis of breathing function measurements revealed a significant decrease in the most relevant respiratory parameters in DMSXL mice, indicating impaired respiratory function. Histological and morphometric analysis showed pathological changes in diaphragmatic muscle of DMSXL mice, characterized by an increase in the percentage of type I muscle fibers, the presence of central nuclei, partial denervation of end-plates (EPs and a significant reduction in their size, shape complexity and density of acetylcholine receptors, all of which reflect a possible breakdown in communication between the diaphragmatic muscles fibers and the nerve terminals. Diaphragm muscle abnormalities were accompanied by an accumulation of mutant DMPK RNA foci in muscle fiber nuclei. Moreover, in DMSXL mice, the unmyelinated phrenic afferents are significantly lower. Also in these mice, significant neuronopathy was not detected in either cervical phrenic motor neurons or brainstem respiratory neurons. Because EPs are involved in the transmission of action potentials and the unmyelinated phrenic afferents exert a modulating influence on the respiratory drive, the pathological alterations affecting these structures might underlie the respiratory impairment detected in DMSXL mice. Understanding

Myotonic Dystrophy Type 1 RNA Crystal Structures Reveal Heterogeneous 1 × 1 Nucleotide UU Internal Loop Conformations

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Kumar, Amit; Park, HaJeung; Fang, Pengfei; Parkesh, Raman; Guo, Min; Nettles, Kendall W.; Disney, Matthew D. (Scripps)

2012-03-27

RNA internal loops often display a variety of conformations in solution. Herein, we visualize conformational heterogeneity in the context of the 5'CUG/3'GUC repeat motif present in the RNA that causes myotonic dystrophy type 1 (DM1). Specifically, two crystal structures of a model DM1 triplet repeating construct, 5'r[{und UU}GGGC(C{und U}G){sub 3}GUCC]{sub 2}, refined to 2.20 and 1.52 {angstrom} resolution are disclosed. Here, differences in the orientation of the 5' dangling UU end between the two structures induce changes in the backbone groove width, which reveals that noncanonical 1 x 1 nucleotide UU internal loops can display an ensemble of pairing conformations. In the 2.20 {angstrom} structure, CUGa, the 5' UU forms a one hydrogen-bonded pair with a 5' UU of a neighboring helix in the unit cell to form a pseudoinfinite helix. The central 1 x 1 nucleotide UU internal loop has no hydrogen bonds, while the terminal 1 x 1 nucleotide UU internal loops each form a one-hydrogen bond pair. In the 1.52 {angstrom} structure, CUGb, the 5' UU dangling end is tucked into the major groove of the duplex. While the canonically paired bases show no change in base pairing, in CUGb the terminal 1 x 1 nucleotide UU internal loops now form two hydrogen-bonded pairs. Thus, the shift in the major groove induced by the 5' UU dangling end alters noncanonical base patterns. Collectively, these structures indicate that 1 x 1 nucleotide UU internal loops in DM1 may sample multiple conformations in vivo. This observation has implications for the recognition of this RNA, and other repeating transcripts, by protein and small molecule ligands.

[Genetic Variability and Structure of SNP Haplotypes in the DMPK Gene in Yakuts and Other Ethnic Groups of Northern Eurasia in Relation to Myotonic Dystrophy].

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Swarovskaya, M G; Stepanova, S K; Marussin, A V; Sukhomyasova, A L; Maximova, N R; Stepanov, V A

2015-06-01

The genetic variability of the DMPK locus has been studied in relation to six SNP markers (rs2070736, rs572634, rs1799894, rs527221, rs915915, and rs10415988) in Yakuts with myotonic dystrophy (MD) in the Yakut population and in populations of northern Eurasia. Significant differences were observed in the allele frequencies between patients and a population sample of Yakuts for three SNP loci (rs915915, rs1799894, and rs10415988) associated with a high chance of disease manifestation. The odds ratios (OR) of MD development in representatives of the Yakut population for these three loci were 2.59 (95% CI, p = 0,004), 4.99 (95% CI, p = 0.000), and 3.15 (95% CI, p = 0.01), respectively. Haplotype TTTCTC, which is associated with MD, and haplotype GTCCTT, which was observed only in Yakut MD patients (never in MD patients of non-Yakut origin), were revealed. A low level of variability in the locus of DMRK gene in Yakuts (H(e) = 0.283) compared with other examined populations was noted. An analysis of pairwise genetic relationships between populations revealed their significant differentiation for all the examined loci. In addition, a low level of differentiation in territorial groups of Yakut populations (F(ST) = 0.79%), which was related to the high subdivision of the northern Eurasian population (F(ST) = 11.83%), was observed.

Overexpression of microRNA-206 in the skeletal muscle from myotonic dystrophy type 1 patients

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Angelini Corrado

2010-05-01

Full Text Available Abstract Background MicroRNAs are highly conserved, noncoding RNAs involved in post-transcriptional gene silencing. They have been shown to participate in a wide range of biological processes, including myogenesis and muscle regeneration. The goal of this study is to test the hypothesis that myo-miRs (myo = muscle + miR = miRNA expression is altered in muscle from patients affected by myotonic dystrophy type 1 (DM1, the most frequently inherited neuromuscular disease in adults. In order to gain better insights about the role of miRNAs in the DM1 pathogenesis, we have also analyzed the muscular expression of miR-103 and miR-107, which have been identified in silico as attractive candidates for binding to the DMPK mRNA. Methods To this aim, we have profiled the expression of miR-133 (miR-133a, miR-133b, miR-1, miR-181 (miR-181a, miR-181b, miR-181c and miR-206, that are specifically induced during myogenesis in cardiac and skeletal muscle tissues. miR-103 and miR-107, highly expressed in brain, heart and muscle have also been included in this study. QRT-PCR experiments have been performed on RNA from vastus lateralis biopsies of DM1 patients (n = 7 and control subjects (n = 4. Results of miRNAs expression have been confirmed by Northern blot, whereas in situ hybridization technique have been performed to localize misexpressed miRNAs on muscle sections from DM1 and control individuals. Results Only miR-206 showed an over-expression in 5 of 7 DM1 patients (threshold = 2, fold change between 1.20 and 13.22, average = 5.37 compared to the control group. This result has been further confirmed by Northern blot analysis (3.37-fold overexpression, R2 = 0.89. In situ hybridization localized miR-206 to nuclear site both in normal and DM1 tissues. Cellular distribution in DM1 tissues includes also the nuclear regions of centralized nuclei, with a strong signal corresponding to nuclear clumps. Conclusions This work provides, for the first time, evidences about

Divergent mitochondrial and endoplasmic reticulum association of DMPK splice isoforms depends on unique sequence arrangements in tail anchors.

NARCIS (Netherlands)

Herpen, R.E.M.A. van; Oude Ophuis, R.J.A.; Wijers-Rouw, M.J.P.; Bennink, M.B.; Loo, F.A.J. van de; Fransen, J.; Wieringa, B.; Wansink, D.G.

2005-01-01

Myotonic dystrophy protein kinase (DMPK) is a Ser/Thr-type protein kinase with unknown function, originally identified as the product of the gene that is mutated by triplet repeat expansion in patients with myotonic dystrophy type 1 (DM1). Alternative splicing of DMPK transcripts results in multiple

X-rays computed tomographic scans of lower limb and trunk muscles in facioscapulohumeral muscular dystrophy

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Horikawa, Hirosei; Mano, Yukio; Takayanagi, Tetsuya [Nara Medical Univ., Kashihara (Japan); Takahashi, Keiichi; Nishio, Hisahide

1992-10-01

X-rays computed tomographic (CT) scans of muscles of the lower limbs and the trunk in 14 patients with facioscapulohumeral muscular dystrophy (FSH) were studied. The CT scans showed that the affected muscles were decreased in density and size. The laterality of muscular involvement was sometimes observed. The muscular lesions in the lower limbs showed proximal distribution. In the thigh, the hamstrings were affected first, the adductor muscles second, and then the muscular involvement progressed to the quadriceps femoris muscle. In the lower leg, the gastrocnemius and soleus muscles were relatively spared as compared with the tibialis anterior muscle. In the lumbar girdle, the abdominal muscles were involved first, the gluteal muscles second, the back muscles third, and the psoas major muscle were relatively spared. The muscular weakness of this distribution exacerbated lumbar lordosis. The neck muscles were less affected than those of the lumbar girdle. The CT scans in FSH demonstrated the characteristic pattern of muscular involvement, which differed from the inherited muscular diseases such as Duchenne muscular dystrophy, myotonic dystrophy, and others. (author).

X-rays computed tomographic scans of lower limb and trunk muscles in facioscapulohumeral muscular dystrophy

International Nuclear Information System (INIS)

Horikawa, Hirosei; Mano, Yukio; Takayanagi, Tetsuya; Takahashi, Keiichi; Nishio, Hisahide.

1992-01-01

X-rays computed tomographic (CT) scans of muscles of the lower limbs and the trunk in 14 patients with facioscapulohumeral muscular dystrophy (FSH) were studied. The CT scans showed that the affected muscles were decreased in density and size. The laterality of muscular involvement was sometimes observed. The muscular lesions in the lower limbs showed proximal distribution. In the thigh, the hamstrings were affected first, the adductor muscles second, and then the muscular involvement progressed to the quadriceps femoris muscle. In the lower leg, the gastrocnemius and soleus muscles were relatively spared as compared with the tibialis anterior muscle. In the lumbar girdle, the abdominal muscles were involved first, the gluteal muscles second, the back muscles third, and the psoas major muscle were relatively spared. The muscular weakness of this distribution exacerbated lumbar lordosis. The neck muscles were less affected than those of the lumbar girdle. The CT scans in FSH demonstrated the characteristic pattern of muscular involvement, which differed from the inherited muscular diseases such as Duchenne muscular dystrophy, myotonic dystrophy, and others. (author)

Disabilities caused by unstable mutations in Costa Rica

OpenAIRE

Morales Montero, Fernando; Cuenca Berger, Patricia; Castro Volio, Isabel

2004-01-01

Myotonic dystrophy and fragile X syndrome are two genetically determined relatively common disabilities. Both are examples of a new type of mutation mechanism called unstable or dynamic mutations, triple repeats expansions or DNA amplification. Fragile X syndrome is recognized as the main cause of hereditary mental retardation and myotonic dystrophy is considered the most common muscular dystrophy of adults. This is a prospective non randomized study of clinically affected people,...

Types of CMT

Science.gov (United States)

... Marie-Tooth Disease (CMT) Congenital Muscular Dystrophy (CMD) Duchenne Muscular Dystrophy (DMD) Emery-Dreifuss Muscular Dystrophy Endocrine Myopathies Metabolic Diseases of Muscle Mitochondrial Myopathies (MM) Myotonic Dystrophy (DM) Spinal-Bulbar ...

Dermatomyositis: Signs and Symptoms

Science.gov (United States)

... Marie-Tooth Disease (CMT) Congenital Muscular Dystrophy (CMD) Duchenne Muscular Dystrophy (DMD) Emery-Dreifuss Muscular Dystrophy Endocrine Myopathies Metabolic Diseases of Muscle Mitochondrial Myopathies (MM) Myotonic Dystrophy (DM) Spinal-Bulbar ...

Dermatomyositis: Diagnosis

Science.gov (United States)

... Marie-Tooth Disease (CMT) Congenital Muscular Dystrophy (CMD) Duchenne Muscular Dystrophy (DMD) Emery-Dreifuss Muscular Dystrophy Endocrine Myopathies Metabolic Diseases of Muscle Mitochondrial Myopathies (MM) Myotonic Dystrophy (DM) Spinal-Bulbar ...

Signs and Symptoms

Science.gov (United States)

... Marie-Tooth Disease (CMT) Congenital Muscular Dystrophy (CMD) Duchenne Muscular Dystrophy (DMD) Emery-Dreifuss Muscular Dystrophy Endocrine Myopathies Metabolic Diseases of Muscle Mitochondrial Myopathies (MM) Myotonic Dystrophy (DM) Spinal-Bulbar ...

Polymyositis: Diagnosis

Science.gov (United States)

... Marie-Tooth Disease (CMT) Congenital Muscular Dystrophy (CMD) Duchenne Muscular Dystrophy (DMD) Emery-Dreifuss Muscular Dystrophy Endocrine Myopathies Metabolic Diseases of Muscle Mitochondrial Myopathies (MM) Myotonic Dystrophy (DM) Spinal-Bulbar ...

Causes of Charcot-Marie-Tooth Disease (CMT)

Science.gov (United States)

... Marie-Tooth Disease (CMT) Congenital Muscular Dystrophy (CMD) Duchenne Muscular Dystrophy (DMD) Emery-Dreifuss Muscular Dystrophy Endocrine Myopathies Metabolic Diseases of Muscle Mitochondrial Myopathies (MM) Myotonic Dystrophy (DM) Spinal-Bulbar ...

Estudo psicológico longitudinal na distrofia miotônica Longitudinal psychologie study in myotonic dystrophy

Directory of Open Access Journals (Sweden)

Cristina Maria Duarte Wigg

1995-12-01

Full Text Available Realizou-se estudo longitudinal das alterações cognitivas de 12 casos de distrofia miotônica comparando os resultados de dois exames com intervalo de tempo entre eles, pois em uma primeira avaliação detectaram-se alterações vísuo-espaciais e construtivas que poderiam evoluir ou não com o passar do tempo. Foram aplicados os seguintes instrumentos de medidas psicológicas: matrizes progressivas de Raven (escala especial forma caderno para as crianças, adolescentes e adultos com dificuldades cognitivas graves e escala geral para adolescentes e adultos sem dificuldades cognitivas graves, Wechsler (escala para crianças, subtestes semelhanças e números, cubos de Kohs e Piaget-Head. A seleção dos testes e respectivas escalas e formas teve como referencial as entrevistas psicológicas realizadas caso a caso. Estes instrumentos com respectivos resultados foram comparados em cada caso através de duas avaliações, com um intervalo de aproximadamente três anos e meio entre a primeira e a segunda avaliações de cada teste. Quanto ao desempenho nos testes, verificamos: (a melhor desempenho estatisticamente significante na segunda avaliação pelo teste dos Cubos de Kohs, porém tanto o primeiro quanto o segundo exame denotaram desempenhos bastante insuficientes; (b leve queda do desempenho no teste de Head 1-3; (c leve melhora nos demais testes.The authors studied in two occasions a group of 12 patients with myotonic dystrophy in a mean interval of three years and a half between the examinations. The neuro - psychological battery included the following tests: Raven's progressive matrices (coloured and general scales , Wechsler children intelligence scale (WISC, Kohs' blocks and Piaget-Head. 50% of the patients had better scores on the second examination on RCPM, 81.89% on WISC-digit span, 63.67% on WISC-numbers, 44.44% on Piaget-Head 2 and 60% on Kohs' blocks. However, on Piaget-Head 1-3, the majority had worse results (87.56% with

Weakness

Science.gov (United States)

... by a slipped disk in the spine) Stroke MUSCLE DISEASES Becker muscular dystrophy Dermatomyositis Muscular dystrophy (Duchenne) Myotonic dystrophy POISONING Botulism Poisoning ( insecticides , nerve gas) ...

Swallowing disorders in muscular diseases: functional assessment and indications of cricopharyngeal myotomy.

Science.gov (United States)

St Guily, J L; Périé, S; Willig, T N; Chaussade, S; Eymard, B; Angelard, B

1994-01-01

Thirty-four patients with an identified muscular disease were referred to our department for assessment and treatment of swallowing difficulties. Their ages ranged from 16 to 91 years (mean 59). The diagnoses were oculopharyngeal dystrophy in 17 patients, Steinert myotonic dystrophy in 6, mitochondrial myopathies in 4, polymyositis in 3, and other types in 4 patients. The main consequences of the dysphagia were weight loss (12 patients), pulmonary infections (15 patients), modified food consistency (18 patients) and non-oral feeding (3 patients). Several techniques were used to assess the different stages of deglutition: physical examination during swallowing, videofluoroscopy, pharyngoesophageal manometry, videofibroscopy of the pharynx during swallowing. Major pathological features found in the pharynx were decreased pharynx peristaltis and impaired UES relaxation. Cricopharyngeal myotomy was performed in 11 myopathic patients (median follow-up 24.9 months), while it was unnecessary, refused or contraindicated in the other patients. The procedure was successful in 8 patients whose dysphagia was dramatically improved, and failed in 3 patients. Pharyngeal perstaltis was severely impaired only in the 3 failures and was partly preserved in the improved cases. We conclude that pharyngeal function is the major prognostic factor. Cricopharyngeal myotomy is an effective treatment in those cases where cricopharyngeal dysfunction is a predominant problem or where pharyngeal peristaltis is partly impaired, since the procedure removes one obstacle. It is contraindicated when pharynx propulsion is severely impaired.

Design of a Bioactive Small Molecule that Targets the Myotonic Dystrophy Type 1 RNA Via an RNA Motif-Ligand Database & Chemical Similarity Searching

Science.gov (United States)

Parkesh, Raman; Childs-Disney, Jessica L.; Nakamori, Masayuki; Kumar, Amit; Wang, Eric; Wang, Thomas; Hoskins, Jason; Tran, Tuan; Housman, David; Thornton, Charles A.; Disney, Matthew D.

2012-01-01

Myotonic dystrophy type 1 (DM1) is a triplet repeating disorder caused by expanded CTG repeats in the 3′ untranslated region of the dystrophia myotonica protein kinase (DMPK) gene. The transcribed repeats fold into an RNA hairpin with multiple copies of a 5′CUG/3′GUC motif that binds the RNA splicing regulator muscleblind-like 1 protein (MBNL1). Sequestration of MBNL1 by expanded r(CUG) repeats causes splicing defects in a subset of pre-mRNAs including the insulin receptor, the muscle-specific chloride ion channel, Sarco(endo)plasmic reticulum Ca2+ ATPase 1 (Serca1/Atp2a1), and cardiac troponin T (cTNT). Based on these observations, the development of small molecule ligands that target specifically expanded DM1 repeats could serve as therapeutics. In the present study, computational screening was employed to improve the efficacy of pentamidine and Hoechst 33258 ligands that have been shown previously to target the DM1 triplet repeat. A series of inhibitors of the RNA-protein complex with low micromolar IC50’s, which are >20-fold more potent than the query compounds, were identified. Importantly, a bis-benzimidazole identified from the Hoechst query improves DM1-associated pre-mRNA splicing defects in cell and mouse models of DM1 (when dosed with 1 mM and 100 mg/kg, respectively). Since Hoechst 33258 was identified as a DM1 binder through analysis of an RNA motif-ligand database, these studies suggest that lead ligands targeting RNA with improved biological activity can be identified by using a synergistic approach that combines analysis of known RNA-ligand interactions with virtual screening. PMID:22300544

Gender as a Modifying Factor Influencing Myotonic Dystrophy Type 1 Phenotype Severity and Mortality: A Nationwide Multiple Databases Cross-Sectional Observational Study.

Directory of Open Access Journals (Sweden)

Celine Dogan

Full Text Available Myotonic Dystrophy type 1 (DM1 is one of the most heterogeneous hereditary disease in terms of age of onset, clinical manifestations, and severity, challenging both medical management and clinical trials. The CTG expansion size is the main factor determining the age of onset although no factor can finely predict phenotype and prognosis. Differences between males and females have not been specifically reported. Our aim is to study gender impact on DM1 phenotype and severity.We first performed cross-sectional analysis of main multiorgan clinical parameters in 1409 adult DM1 patients (>18 y from the DM-Scope nationwide registry and observed different patterns in males and females. Then, we assessed gender impact on social and economic domains using the AFM-Téléthon DM1 survey (n = 970, and morbidity and mortality using the French National Health Service Database (n = 3301.Men more frequently had (1 severe muscular disability with marked myotonia, muscle weakness, cardiac, and respiratory involvement; (2 developmental abnormalities with facial dysmorphism and cognitive impairment inferred from low educational levels and work in specialized environments; and (3 lonely life. Alternatively, women more frequently had cataracts, dysphagia, digestive tract dysfunction, incontinence, thyroid disorder and obesity. Most differences were out of proportion to those observed in the general population. Compared to women, males were more affected in their social and economic life. In addition, they were more frequently hospitalized for cardiac problems, and had a higher mortality rate.Gender is a previously unrecognized factor influencing DM1 clinical profile and severity of the disease, with worse socio-economic consequences of the disease and higher morbidity and mortality in males. Gender should be considered in the design of both stratified medical management and clinical trials.

Effect of dual-chamber minimal ventricular pacing on paroxysmal atrial fibrillation incidence in myotonic dystrophy type 1 patients: A prospective, randomized, single-blind, crossover study.

Science.gov (United States)

Russo, Vincenzo; Papa, Andrea Antonio; Rago, Anna; Ciardiello, Carmine; Nigro, Gerardo

2018-03-08

Atrial fibrillation (AF) is a common finding in the myotonic dystrophy type 1 (DM1) population. Pacemakers (PMs) may facilitate the diagnosis and management of frequent subclinical asymptomatic AF episodes. The purpose of this study was to evaluate the effect of minimal ventricular pacing on paroxysmal AF incidence in DM1 patients during a 24-month follow-up period. We enrolled 70 DM1 patients (age 43.4 ± 13.8 years; 39 women) who underwent dual-chamber PM implantation. Patients were randomized to minimizing ventricular pacing features (ON) or not (OFF). Patients crossed over to the opposite pacing programming 12 months later. We counted the number of DM1 patients with at least 1 episode of AF, the AF total duration, and the burden recorded by PM diagnostics during the MVP ON and OFF phases. Twenty-five DM1 patients (41.7%) showed at least 1 AF episode. Seven patients (11.7%) demonstrated AF episodes during MVP ON phase and 25 patients (41.7%) during MVP OFF phase (P MVP ON or OFF phase, 3 patients had AF episodes only during MVP ON phase, 21 patients had AF episodes only during MVP OFF phase, and 4 patients had AF episodes during MVP ON and OFF phases. Activation of the MVP algorithm was associated with a 44% reduction in relative risk of developing AF. Furthermore, during the MVP ON phases, the study population showed a shorter total AF duration and a lower AF burden. MVP is an efficacy strategy for reducing the risk of AF in DM1 patients who have undergone PM implantation. Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Is one trial enough for repeated testing? Same-day assessments of walking, mobility and fine hand use in people with myotonic dystrophy type 1.

Science.gov (United States)

Kierkegaard, Marie; Petitclerc, Emilie; Hébert, Luc J; Gagnon, Cynthia

2017-02-01

Performance-based assessments of physical function are essential in people with myotonic dystrophy type 1 (DM1) to monitor disease progression and evaluate interventions. Commonly used are the six-minute walk test, the 10 m-walk test, the timed up-and-go test, the timed-stands test, grip strength tests and the nine-hole peg test. The number of trials needed on a same-day test occasion and whether the first, best or average of trials should be reported as result is unknown. Thus, the aim was to describe and explore differences between trials in these measures of walking, mobility and fine hand use in 70 adults with DM1. Three trials were performed for each test except for the six-minute walk test where two trials were allowed. There were statistical significant differences over trials in all tests except for the 10 m-walk test and grip strength tests. Pair-wise comparisons showed that the second and third trials were in general better than the first, although effect sizes were small. At which trial the individuals performed their best differed between individuals and tests. People with severe muscular impairment had difficulties to perform repeated trials. Intraclass correlation coefficients were all high in analyses exploring how to report results. The conclusion and clinical implication is that, for a same-day test occasion, one trial is sufficient for the 10 m-walk test and grip strength tests, and that repeated trials should be allowed in the timed up-and-go test, timed-stands test and nine-hole peg tests. We recommend that two trials are performed for these latter tests as such a protocol could accommodate people with various levels of impairments and physical limitations. Copyright © 2016 Elsevier B.V. All rights reserved.

Clinical trial network for the promotion of clinical research for rare diseases in Japan: muscular dystrophy clinical trial network.

Science.gov (United States)

Shimizu, Reiko; Ogata, Katsuhisa; Tamaura, Akemi; Kimura, En; Ohata, Maki; Takeshita, Eri; Nakamura, Harumasa; Takeda, Shin'ichi; Komaki, Hirofumi

2016-07-11

Duchenne muscular dystrophy (DMD) is the most commonly inherited neuromuscular disease. Therapeutic agents for the treatment of rare disease, namely "orphan drugs", have recently drawn the attention of researchers and pharmaceutical companies. To ensure the successful conduction of clinical trials to evaluate novel treatments for patients with rare diseases, an appropriate infrastructure is needed. One of the effective solutions for the lack of infrastructure is to establish a network of rare diseases. To accomplish the conduction of clinical trials in Japan, the Muscular dystrophy clinical trial network (MDCTN) was established by the clinical research group for muscular dystrophy, including the National Center of Neurology and Psychiatry, as well as national and university hospitals, all which have a long-standing history of research cooperation. Thirty-one medical institutions (17 national hospital organizations, 10 university hospitals, 1 national center, 2 public hospitals, and 1 private hospital) belong to this network and collaborate to facilitate clinical trials. The Care and Treatment Site Registry (CTSR) calculates and reports the proportion of patients with neuromuscular diseases in the cooperating sites. In total, there are 5,589 patients with neuromuscular diseases in Japan and the proportion of patients with each disease is as follows: DMD, 29 %; myotonic dystrophy type 1, 23 %; limb girdle muscular dystrophy, 11 %; Becker muscular dystrophy, 10 %. We work jointly to share updated health care information and standardized evaluations of clinical outcomes as well. The collaboration with the patient registry (CTSR), allows the MDCTN to recruit DMD participants with specific mutations and conditions, in a remarkably short period of time. Counting with a network that operates at a national level is important to address the corresponding national issues. Thus, our network will be able to contribute with international research activity, which can lead to

Evaluation of myocardial involvement in muscular dystrophy with Thallium-201 emission computed tomography

International Nuclear Information System (INIS)

Yamamoto, S.; Kawai, N.; Matsushima, H.; Okada, M.; Yamauchi, K.; Yokota, M.; Hayashi, H.; Sotobata, I.; Sakuma, S.

1985-01-01

The clinical usefulness of quantitative analysis of thallium-201 emission computed tomography (ECT) for evaluation of left ventricular myocardial fibrosis was assessed on 45 patients with Duchenne(D), facioscapulohumeral(FSH), limbgirdle(LG) and myotonic(M) dystrophy. Trans-,long- and short-axial images were interpreted quantitatively using circumferential profile analysis, and the fibrotic tissue size (%FIB) was estimated by integration of hypoperfused areas in 6 to 8 consecutive short-axial slices. Lung/mediastinum count ratios (L/M ratio) were also assessed. Distinct ECT defects were found in 42 patients (all cases of D, FSH and LG, and 2 of 5 MTs). ECT defects were observed specifically in the posterolateral wall (71%) and apex (58%) in D, and were scattered in all LV walls in FSHG, LG and MT. ECG and VCG underestimated the extent of myocardial fibrosis in 17 patients (40%). Percent FIBs coincided with fibrotic tissue sizes proven by autopsy. Body-surface ECG should be influenced by cardiac position and rotation in the thorax, which were often observed in these disease entities. These factors were also assessed with ECT. The authors conclude; ECT to be useful for non-invasive evaluation of myocardial fibrosis in patients with various types of muscular dystrophy

Evaluation of myocardial involvement in muscular dystrophy with thallium-201 emission computed tomography

International Nuclear Information System (INIS)

Yamamoto, Shuhei; Sotobata, Iwao; Indo, Toshikatsu; Matsuoka, Yukihiko; Kawai, Naoki; Matsushima, Hideo; Suzuki, Akio; Abe, Tetsutaro; Sakuma, Sadayuki

1986-01-01

The clinical usefulness of thallium-201 myocardial perfusion scanning with emission computed tomography (ECT) for evaluation of left ventricular myocardial fibrosis was assessed on 47 patients with Duchenne (DMD), facioscapulohumeral (FSH), limb-girdle (LG) and myotonic (MT) dystrophy. Trans-, long- and short-axial images were interpreted quantitatively by circumferential profile analysis, and the fibrotic tissue size (%FIB) was estimated by integration of hypoperfused areas in 6 to 8 consecutive short-axial slices. Lung/mediastinum count ratios (L/M ratio), LV cavity dilatation, aneurysm formation and cardiac malrotations were also assessed with ECT. Distinct ECT perfusion defect was observed in 26 of 29 DMDs, and in 11 of 18 patients with other types. Perfusion defect was demonstrated in 95 of total 235 segments, and was observed specifically in the posterior wall (82 %) and the apex (65 %) in DMD, and was scattered in all LV wall segments in FSH, LG, and MT. Percent FIB correlated significantly with L/M ratio (r = 0.82, p < 0.01), and did not with age or clinical stage score. ECT showed marked LV dilatation in 7, apical aneurysm in 5 and cardiac malrotation in 23 of the 47 patients. In conclusion, ECT was considered to be a useful clinical means of evaluating myocardial involvement in patients with muscular dystrophy. (author)

Cortical and Subcortical Grey and White Matter Atrophy in Myotonic Dystrophies Type 1 and 2 Is Associated with Cognitive Impairment, Depression and Daytime Sleepiness.

Directory of Open Access Journals (Sweden)

Christiane Schneider-Gold

Full Text Available Central nervous system involvement is one important clinical aspect of myotonic dystrophy type 1 and 2 (DM1 and DM2. We assessed CNS involvement DM1 and DM2 by 3T MRI and correlated clinical and neuocognitive symptoms with brain volumetry and voxel-based morphometry (VBM.12 patients with juvenile or classical DM1 and 16 adult DM2 patients underwent 3T MRI, a thorough neurological and neuropsychological examination and scoring of depression and daytime sleepiness. Volumes of brain, ventricles, cerebellum, brainstem, cervical cord, lesion load and VBM results of the patient groups were compared to 33 matched healthy subjects.Clinical symptoms were depression (more pronounced in DM2, excessive daytime sleepiness (more pronounced in DM1, reduced attention and flexibility of thinking, and deficits of short-term memory and visuo-spatial abilities in both patient groups. Both groups showed ventricular enlargement and supratentorial GM and WM atrophy, with prevalence for more GM atrophy and involvement of the motor system in DM1 and more WM reduction and affection of limbic structures in DM2. White matter was reduced in DM1 in the splenium of the corpus callosum and in left-hemispheric WM adjacent to the pre- and post-central gyrus. In DM2, the bilateral cingulate gyrus and subgyral medio-frontal and primary somato-sensory WM was affected. Significant structural-functional correlations of morphological MRI findings (global volumetry and VBM with clinical findings were found for reduced flexibility of thinking and atrophy of the left secondary visual cortex in DM1 and of distinct subcortical brain structures in DM2. In DM2, depression was associated with brainstem atrophy, Daytime sleepiness correlated with volume decrease in the middle cerebellar peduncles, pons/midbrain and the right medio-frontal cortex.GM and WM atrophy was significant in DM1 and DM2. Specific functional-structural associations related morphological changes to cognitive impairment

Derivation of Human Induced Pluripotent Stem (iPS) Cells to Heritable Cardiac Arrhythmias

Science.gov (United States)

2017-08-10

Inherited Cardiac Arrythmias; Long QT Syndrome (LQTS); Brugada Syndrome (BrS); Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT); Early Repolarization Syndrome (ERS); Arrhythmogenic Cardiomyopathy (AC, ARVD/C); Hypertrophic Cardiomyopathy (HCM); Dilated Cardiomyopathy (DCM); Muscular Dystrophies (Duchenne, Becker, Myotonic Dystrophy); Normal Control Subjects

Employment status of patients with neuromuscular diseases in relation to personal factors, fatigue and health status: a secondary analysis.

NARCIS (Netherlands)

Minis, M.A.H; Kalkman, J.S.; Akkermans, R.P.; Engels, J.A.; Huijbregts, P.A.; Bleijenberg, G.; Oostendorp, R.A.B.; Engelen, B.G.M. van

2010-01-01

OBJECTIVE: To determine the number of employed people in a group of patients with neuromuscular diseases and in 3 separate subgroups (facioscapulo-humeral dystrophy, hereditary motor and sensory neuropathy, and myotonic dystrophy) to investigate any differences in employment status between the

Hipotonia Esclarecida com um Aperto de Mão. Doença de Steinert

OpenAIRE

Marques, M. Eduarda; Antunes, Henedina; Reis, Helena Cunha

2014-01-01

Os AAs apresentam o caso clínico de uma criança de 4 anos seguida no Hospital de São Marcos por Doença de Steinert lá diagnosticada aos 4meses. Apresentava hipotonia generalizada com diminuição dos reflexos osteotendinosos, hipotrofia dos músculos temporais, pseudodiplegia da face,lábio superior em acento circunflexo, dificuldade em deglutir, choro fraco, sopro cardíaco e pés botos.A mãe tinha baixa estatura, voz peculiar, face inexpressiva e apresentava miotonia expressa por dificuldade em s...

Employment status of patients with neuromuscular diseases in relation to personal factors, fatigue and health status : A secondary analysis

NARCIS (Netherlands)

Rob Oostendorp; Peter Huijbregts; Marie-Antoinette Minis; Joke Kalkman; Baziel Engelen; Reinier Akkermans; Gijs Bleijenberg; Josephine Engels

2010-01-01

To determine the number of employed people in a group of patients with neuromuscular diseases and in 3 separate subgroups (facioscapulo-humeral dystrophy, hereditary motor and sensory neuropathy, and myotonic dystrophy) to investigate any differences in employment status between the patient groups,

Síndrome de Steinert no âmbito da Medicina Dentária

OpenAIRE

Baptista, Helena Marisa Gonçalves

2015-01-01

Projeto de Pós-Graduação/Dissertação apresentado à Universidade Fernando Pessoa como parte dos requisitos para obtenção do grau de Mestre em Medicina Dentária A síndrome de Steinert, ou distrofia miotónica tipo 1, é uma patologia resultante de mutações genéticas, caracterizada por miotonia e por apresentar um quadro clínico multisistémico que afeta vários tecidos do corpo humano, incluindo os músculos, provocando fenótipos de fraqueza, debilidade muscular e redução da força do músculo. Des...

Author Details

African Journals Online (AJOL)

Cherti, M. Vol 20, No 1 (2015) - Articles Atteinte cardiaque au cours de la dystrophie myotonique de Steinert: Expérience marocaine, à propos de 18 cas. Abstract · Vol 21, No 1 (2015) - Articles Recurrent myocardial infarction in a young cocaine abuser. Abstract PDF. ISSN: 1937-8688. AJOL African Journals Online.

Analysis of CTG repeat length variation in the DMPK gene in the general population and the molecular diagnosis of myotonic dystrophy type 1 in Malaysia.

Science.gov (United States)

Ambrose, Kathlin K; Ishak, Taufik; Lian, Lay-Hoong; Goh, Khean-Jin; Wong, Kum-Thong; Ahmad-Annuar, Azlina; Thong, Meow-Keong

2017-03-31

The lack of epidemiological data and molecular diagnostic services in Malaysia has hampered the setting-up of a comprehensive management plan for patients with myotonic dystrophy type 1 (DM1), leading to delayed diagnosis, treatment and support for patients and families. The aim of this study was to estimate the prevalence of DM1 in the 3 major ethnic groups in Malaysia and evaluate the feasibility of a single tube triplet-primed PCR (TP-PCR) method for diagnosis of DM1 in Malaysia. We used PCR to determine the size of CTG repeats in 377 individuals not known to be affected by DM and 11 DM1 suspected patients, recruited from a tertiary hospital in Kuala Lumpur. TP-PCR was performed on selected samples, followed by Southern blot hybridisation of PCR amplified fragments to confirm and estimate the size of CTG expansion. The number of individuals not known to be affected by DM with (CTG) >18 was determined according to ethnic group and as a whole population. The χ 2 test was performed to compare the distribution of (CTG) >18 with 12 other populations. Additionally, the accuracy of TP-PCR in detecting CTG expansion in 11 patients with DM1 was determined by comparing the results with that from Southern blot hybridisation. Of the 754 chromosomes studied, (CTG) >18 frequency of 3.60%, 1.57% and 4.00% in the Malay, Chinese and Indian subpopulations, respectively, was detected, showing similarities to data from Thai, Taiwanese and Kuwaiti populations. We also successfully detected CTG expansions in 9 patients using the TP-PCR method followed by the estimation of CTG expansion size via Southern blot hybridisation. The results show a low DM1 prevalence in Malaysia with the possibility of underdiagnosis and demonstrates the feasibility of using a clinical and TP-PCR-based approach for rapid and cost-effective DM1 diagnosis in developing countries. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Reproducible measurements of muscle characteristics using the MyotonPRO device : comparison between individuals with and without paratonia

NARCIS (Netherlands)

Van Deun, Bieke; Cagnie, Barbara; Van Eetvelde, Birgit; Van Den Noortgate, Nele; Cambier, Dirk; Hobbelen, Hans

2016-01-01

BACKGROUND AND PURPOSE: The MyotonPRO is a portable device that measures muscle tone and biomechanical muscle properties objectively. MyotonPRO has already proven to be effective in measuring muscle properties in healthy and diseased populations. However, to the best of our knowledge, it has never

Apport des techniques non invasives dans le suivi de l'atteinte cardiaque dans la maladie de Steinert

OpenAIRE

Luporsi , Jean-Dominique

2008-01-01

The first part of this personal work is a review focused on epidemiology, genetic bases,clinical description and treatment of Steinert's disease. The second part exposes a personal trial based on the recruitment of 102 patients coming from the orphan diseases and the neurology departments of the Nancy universitary hospital, who are then sent to the cardiology department for systematic non-invasive investigations in the framework of their myotonicdystrophy. A comparison is made between Our res...

[Development, problems and results of specialty-specific genetic counseling at the Neurology Clinic of the Karl Marx University].

Science.gov (United States)

Bachmann, H

1987-11-01

Genetic counselling for inherited neurological diseases has been established at the Clinic for Neurology of Karl Marx University. Comprehensive experiences have been got with the specific and sometimes markedly different problems and aims of counselling in Wilsons disease, X-linked recessive muscular dystrophies, myotonic dystrophy and other neuromuscular disorders, Huntingtons chorea and hereditary ataxias.

Learning about Myotonic Dystrophy

Science.gov (United States)

... Care Genomic Medicine Working Group New Horizons and Research Patient Management Policy and Ethics Issues Quick Links for Patient Care Education All About the Human Genome Project Fact Sheets Genetic Education Resources for ...

Cardiac involvement in children with neuro-muscular disorders

Directory of Open Access Journals (Sweden)

E. N. Arkhipova

2015-01-01

Full Text Available Many inherited neuromuscular disorders include cardiac involvement as a typical clinical feature. Among the most common of them is the group of muscular dystrophies. Dilated cardiomyopathy, ventricular arrhythmias, atrial fibrillations, atrioventricular and intraventricular conduction abnormalities, and sudden cardiac death are well known pathological findings in Duchenne muscular dystrophies, myotonic dystrophy type I and 2, Emery-Dreifuss muscular dystrophies and different types of limb-girdle muscular dystrophies and other disorders. Detection of cardiac pathology in patients with different muscular dystrophies is possible with ECG, echocardiography and cardiovascular magnetic resonance imaging, which are recommended for screening and early cardioprotective treatment.

Comparative study of thallium-201 single-photon emission computed tomography and electrocardiography in Duchenne and other types of muscular dystrophy

International Nuclear Information System (INIS)

Yamamoto, S.; Matsushima, H.; Suzuki, A.; Sotobata, I.; Indo, T.; Matsuoka, Y.

1988-01-01

Single-photon emission computed tomography (SPECT) using thallium-201 was compared with 12-lead electrocardiography (ECG) in patients with Duchenne (29), facioscapulohumeral (7), limb-girdle (6) and myotonic (5) dystrophies, by dividing the left ventricular (LV) wall into 5 segments. SPECT showed thallium defects (37 patients, mostly in the posteroapical wall), malrotation (23), apical aneurysm (5) and dilatation (7). ECG showed abnormal QRS (36 patients), particularly as a posterolateral pattern (13). Both methods of assessment were normal in only 7 patients. The Duchenne type frequently showed both a thallium defect (particularly in the posteroapical wall) and an abnormal QRS (predominantly in the posterolateral wall); the 3 other types showed abnormalities over the 5 LV wall segments in both tests. The percent of agreement between the 2 tests was 64, 66, 70, 72 and 72 for the lateral, apical, anteroseptal, posterior and inferior walls, respectively. The 2 tests were discordant in 31% of the LV wall, with SPECT (+) but ECG (-) in 21% (mostly in the apicoinferior wall) and SPECT (-) but ECG (+) in 10% (mostly in the lateral wall). Some patients showed large SPECT hypoperfusion despite minimal electrocardiographic changes. ECG thus appeared to underestimate LV fibrosis and to reflect posteroapical rather than posterolateral dystrophy in its posterolateral QRS pattern. In this disease, extensive SPECT hypoperfusion was also shown, irrespective of clinical subtype and skeletal involvement

Evaluation of Limb-Girdle Muscular Dystrophy

Science.gov (United States)

2014-03-06

Becker Muscular Dystrophy; Limb-Girdle Muscular Dystrophy, Type 2A (Calpain-3 Deficiency); Limb-Girdle Muscular Dystrophy, Type 2B (Miyoshi Myopathy, Dysferlin Deficiency); Limb-Girdle Muscular Dystrophy, Type 2I (FKRP-deficiency)

Genetics Home Reference: myotonic dystrophy

Science.gov (United States)

... 17 [updated 2015 Oct 22]. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews® [Internet]. Seattle (WA): ...

Granular corneal dystrophy Groenouw type I (GrI) and Reis-Bücklers' corneal dystrophy (R-B). One entity?

Science.gov (United States)

Møller, H U

1989-12-01

This paper maintains that Reis-Bücklers' corneal dystrophy and granular corneal dystrophy Groenouw type I are one and the same disease. Included are some of the technically best photographs of Reis-Bücklers' dystrophy found in the literature, and these are compared with photographs from patients with granular corneal dystrophy examined by the author. It is argued that most of the histological and ultrastructural findings on Reis Bücklers' dystrophy described in the literature are either congruent with what is found in granular corneal dystrophy or unspecific.

The heart in Becker muscular dystrophy, facioscapulohumeral dystrophy, and Bethlem myopathy

NARCIS (Netherlands)

de Visser, M.; de Voogt, W. G.; la Rivière, G. V.

1992-01-01

We report a study, assessing involvement of the heart in 33 familial cases of Becker muscular dystrophy (BMD), 31 familiar cases of facioscapulohumeral (FSH) dystrophy, and 27 familial cases of Bethlem myopathy. In the patients with BMD, correlations of myocardial involvement with age and extent of

Congenital myotonic myopathy in the miniature schnauzer: an autosomal recessive trait.

Science.gov (United States)

Vite, C H; Melniczek, J; Patterson, D; Giger, U

1999-01-01

Myotonia is a clinical sign characterized by a delay in skeletal muscle relaxation following electrical or mechanical stimulation. A series of related miniature schnauzer dogs with congenital myotonic myopathy were studied. A composite pedigree of six affected litters and the results of a planned breeding between two affected animals are consistent with an autosomal recessive mode of inheritance.

Rhabdomyolysis featuring muscular dystrophies.

Science.gov (United States)

Lahoria, Rajat; Milone, Margherita

2016-02-15

Rhabdomyolysis is a potentially life threatening condition of various etiology. The association between rhabdomyolysis and muscular dystrophies is under-recognized in clinical practice. To identify muscular dystrophies presenting with rhabdomyolysis at onset or as predominant feature. We retrospectively reviewed clinical and laboratory data of patients with a genetically confirmed muscular dystrophy in whom rhabdomyolysis was the presenting or main clinical manifestation. Thirteen unrelated patients (males=6; females=7) were identified. Median age at time of rhabdomyolysis was 18 years (range, 2-47) and median duration between the first episode of rhabdomyolysis and molecular diagnosis was 2 years. Fukutin-related protein (FKRP) muscular dystrophy (n=6) was the most common diagnosis, followed by anoctaminopathy-5 (n=3), calpainopathy-3 (n=2) and dystrophinopathy (n=2). Four patients experienced recurrent rhabdomyolysis. Eight patients were asymptomatic and 3 reported myalgia and exercise intolerance prior to the rhabdomyolysis. Exercise (n=6) and fever (n=4) were common triggers; rhabdomyolysis was unprovoked in 3 patients. Twelve patients required hospitalization. Baseline CK levels were elevated in all patients (median 1200 IU/L; range, 600-3600). Muscular dystrophies can present with rhabdomyolysis; FKRP mutations are particularly frequent in causing such complication. A persistently elevated CK level in patients with rhabdomyolysis warrants consideration for underlying muscular dystrophy. Copyright © 2015 Elsevier B.V. All rights reserved.

Pilomatricoma in childhood: a retrospective study from three European paediatric centres.

Science.gov (United States)

Cigliano, Bruno; Baltogiannis, Nikolaos; De Marco, Marianna; Faviou, Elsa; Settimi, Alesandro; Tilemis, Stefanos; Soutis, Michail; Papandreou, Evangellos; D'Agostino, Sergio; Fabbro, Maria Angelica

2005-11-01

Pilomatricoma is characterised as a common, slowly growing benign cutaneous tumour that appears generally within the first decades of life. The clinical diagnosis is frequently missed, especially by the paediatrician unfamiliar with these tumours. We present the experience gained in three European tertiary care paediatric centres with the treatment of pilomatricoma and also current data on the aetiology, clinical presentation and management. A retrospective study was carried out in 83 patients suspected for pilomatricoma during a 7-year period (1996-2002) at the departments of Paediatric Surgery of the Children's University Hospital "Federico II", Naples, Hospital "San Bortolo", Vicenza and "Aghia Sophia" Children's Hospital, Athens. The age range was from 10 months to 17 years, median age 8 years. All patients were treated by surgical excision and all specimens were examined by histopathological assessment. The follow-up varied from 5 months to 6 years. The correct diagnosis was made preoperatively in 68 patients (82%). The female/male ratio was 2:1. The sites of occurrence were the head (47.5%), especially in the periorbital region, the neck (9%), the upper limbs (35.5%), the inferior limbs (4%) and the thorax (4%). Each patient exhibited a single pilomatricoma except for two patients who had multiple lesions (2.4%). One of them had Steinert disease (myotonic dystrophy). No recurrences were observed during the follow-up period. Pilomatricoma is one of the most common cutaneous adnexal neoplasms in children. Surgical excision including clear margins and its overlying skin in most cases is the treatment of choice. The recurrence as well as malignant evolution is rare.

Disease impact in chronic progressive external ophthalmoplegia: more than meets the eye

NARCIS (Netherlands)

Smits, B.W.; Fermont, J.; Delnooz, C.C.S.; Kalkman, J.S.; Bleijenberg, G.; Engelen, B.G.M. van

2011-01-01

We determined the extent of disease impact in 28 patients with genetically confirmed chronic progressive external ophthalmoplegia (CPEO) and compared the outcomes to those of matched myotonic dystrophy type I patients. CPEO patients reported a high frequency of severe fatigue (67.9%), pain (96.2%),

Muscular dystrophy in a dog resembling human becker muscular dystrophy.

Science.gov (United States)

Baroncelli, A B; Abellonio, F; Pagano, T B; Esposito, I; Peirone, B; Papparella, S; Paciello, O

2014-05-01

A 3-year-old, male Labrador retriever dog was presented with clinical signs of progressive exercise intolerance, bilateral elbow extension, rigidity of the forelimbs, hindlimb flexion and kyphosis. Microscopical examination of muscle tissue showed marked variability in myofibre size, replacement of muscle with mature adipose tissue and degeneration/regeneration of muscle fibres, consistent with muscular dystrophy. Immunohistochemical examination for dystrophin showed markedly reduced labelling with monoclonal antibodies specific for the rod domain and the carboxy-terminal of dystrophin, while expression of β-sarcoglycan, γ-sarcoglycan and β-dystroglycan was normal. Immunoblotting revealed a truncated dystrophin protein of approximately 135 kDa. These findings supported a diagnosis of congenital canine muscular dystrophy resembling Becker muscular dystrophy in man. Copyright © 2014 Elsevier Ltd. All rights reserved.

Genetics Home Reference: Fukuyama congenital muscular dystrophy

Science.gov (United States)

... with mental retardation Muscular dystrophy, congenital, Fukuyama type Muscular dystrophy, congenital, with central nervous system involvement Polymicrogyria with muscular dystrophy Related Information How ...

Understanding the genetic diversity of South Africa's peoples

African Journals Online (AJOL)

genetic conditions, such as fragile X mental retardation syndrome, myotonic dystrophy ... similar mutations – an area within or close to the gene where there ... risk of having children and grandchildren with severe intellectual disability. Further, the ... cognitive decline and psychiatric symptoms, shows some unique features in ...

Orocaecal transit time in Duchenne muscular dystrophy.

OpenAIRE

Korman, S H; Bar-Oz, B; Granot, E; Meyer, S

1991-01-01

Smooth muscle degeneration may occur in Duchenne muscular dystrophy. We measured fasting orocaecal transit time in patients with advanced Duchenne muscular dystrophy and other muscular dystrophies and in healthy controls. No significant differences were found. In contrast to reports of gastric hypomotility in Duchenne muscular dystrophy, we found no evidence of impaired small intestinal motility.

[30-year-old Patient with suspected Marfan Syndrome and Progressive Gait disturbance].

Science.gov (United States)

Balke, Maryam; Lehmann, Helmar C; Fink, Gereon R; Wunderlich, Gilbert

2017-07-01

History  A 30-year-old man presented with a history of progressive muscle weakness, difficulty in concentrating, and a slender habitus since early childhood. Marfan syndrome was suspected since the age of 14. Examinations  13 years later he was examined by Marfan experts and by genetic testing and Marfan syndrome could not be confirmed. Further neurological examination revealed the suspected diagnosis of myotonic dystrophy type 1, which was confirmed by genetic testing. Treatment and course  Similar to Marfan syndrome, myotonic dystrophy is a multisystemic disorder with the risk of cardiac arrythmias. It is necessary to provide an interdisciplinary care by neurologists, internists, ophthalmologists, speech therapists, and physiotherapists. Conclusion  It is not enough to take the habitus as the principle sign to diagnose Marfan syndrome. Furthermore, it is essential to consider symptoms that are not typical for Marfan syndrome, such as cognitive deficiencies or progressive paresis. © Georg Thieme Verlag KG Stuttgart · New York.

Genetics Home Reference: Duchenne and Becker muscular dystrophy

Science.gov (United States)

... Conditions Duchenne and Becker muscular dystrophy Duchenne and Becker muscular dystrophy Printable PDF Open All Close All Enable Javascript ... dystrophy occur almost exclusively in males. Duchenne and Becker muscular dystrophies have similar signs and symptoms and are caused ...

Quantitative measurement of ventricular dilatation on CT scan

International Nuclear Information System (INIS)

Okita, Naoshi; Mochizuki, Hiroshi; Takase, Sadao

1985-01-01

Cerebral atrophy might be judged from the ventricular dilatation with some indices, calculated from various ventricular width. But, there is no general agreement on what index is the most reliable. In this paper, we attempted to establish the index, easy to measure and most reliable. Our method is as follow. 1) We carried out the CT scan (EMI 1010) on 89 neurologically intact patients. Scans were parallel to orbito-meatal line (OML), and were 10 mm in thickness. On CT scan films, various width, area of anterior horns and area of bodies of lateral ventricles were measured. Measurement about the anterior horns of lateral ventricles were carried out on image the most clearly showed the foramen of Monro. And measurements about the bodies of lateral ventricles were on image, 20 mm above the image of anterior horn. Correlations of various width and areas were calculated. Then we proposed new indices with high correlations (over 0.9) with ventricular area; Anterior horn CVI (Cerebro-Ventricular Index) and Body CVI. 2) Patients with myotonic dystrophy show cerebral atrophy. We carried out the CT scan (GECT/T 8800) on 17 myotonic dystrophy patients and 30 controls. Between the two groups, age and sex were almost matched. In the two groups, we calculated our new indices as well as various indices which have been reported; Huckman number, Bifrontal CVI, Bicaudal CVI, Anterior horn index, Hirajima's index, and Cella-media index. The data were analyzed statistically. The ventricular dilatation of myotonic dystrophy patients is more definite with Anterior horn CVI, Bicaudal CVI and Body CVI (p<0.01). These indices have higher correlations with the ventricular area (about 0.9). (J.P.N.)

Learning disabilities in neuromuscular disorders: a springboard for adult life.

Science.gov (United States)

Astrea, Guja; Battini, Roberta; Lenzi, Sara; Frosini, Silvia; Bonetti, Silvia; Moretti, Elena; Perazza, Silvia; Santorelli, Filippo M; Pecini, Chiara

2016-10-01

Although the presence of cognitive deficits in Duchenne muscular dystrophy or myotonic dystrophy DM1 is well established in view of brain-specific expression of affected muscle proteins, in other neuromuscular disorders, such as congenital myopathies and limb-girdle muscular dystrophies, cognitive profiles are poorly defined. Also, there are limited characterization of the cognitive profile of children with congenital muscular dystrophies, notwithstanding the presence of cerebral abnormality in some forms, and in spinal muscular atrophies, with the exception of distal spinal muscular atrophy (such as the DYN1CH1- associated form). Starting from the Duchenne muscular dystrophy, which may be considered a kind of paradigm for the co-occurrence of learning disabilities in the contest of a progressive muscular involvement, the findings of neuropsychological (or cognitive) dysfunctions in several forms of neuromuscular diseases will be examined and reviewed.

Learning about Duchenne Muscular Dystrophy

Science.gov (United States)

... protein. Often these boys are classified as having Becker muscular dystrophy. Genetic testing (looking at the body's genetic instructions) ... National Library of Medicine Web site Duchenne and Becker muscular dystrophy [ghr.nlm.nih.gov] From Genetics Home Reference ...

A comparison of swallowing dysfunction in Becker muscular dystrophy and Duchenne muscular dystrophy.

Science.gov (United States)

Yamada, Yuka; Kawakami, Michiyuki; Wada, Ayako; Otsuka, Tomoyoshi; Muraoka, Kaori; Liu, Meigen

2018-06-01

Swallowing dysfunction has been reported in Duchenne muscular dystrophy (DMD), but has not been studied in Becker muscular dystrophy (BMD). The aims of this study were to report the characteristics of swallowing dysfunction in BMD compared with DMD. The study participants were 18 patients with BMD and 18 patients with DMD. All the patients were examined using videofluorography during swallowing of 5 mL of fluid. The penetration-aspiration scale (P-A scale) and the videofluorographic dysphagia scale (VDS) were used to evaluate dysphagia. Swinyard functional ability stage was not significantly different between the BMD and DMD groups. Rate of aspiration, P-A scale score, and total VDS score did not differ across groups, but the VDS item score for laryngeal elevation was lower in the BMD group than in the DMD group (median scores 4.5 and 9, respectively; p Becker muscular dystrophy (BMD) was not well known. Eighteen patients with BMD and 18 patients with Duchenne muscular dystrophy were examined with videofluorography. Patients with BMD have swallowing problems similar to those observed in patients with DMD.

Prevalence of generalized retinal dystrophy in Denmark

DEFF Research Database (Denmark)

Bertelsen, Mette; Jensen, Hanne; Bregnhøj, Jesper F

2014-01-01

of this study was to examine the prevalence and diagnostic spectrum of generalized retinal dystrophy in the Danish population. METHODS: A population-based cross-sectional study with data from the Danish Retinitis Pigmentosa Registry that comprises all patients in Denmark with generalized retinal......PURPOSE: Generalized retinal dystrophy is a frequent cause of visual impairment and blindness in younger individuals and a subject of new clinical intervention trials. Nonetheless, there are few nation-wide population-based epidemiological data of generalized retinal dystrophy. The purpose...... and chorioretinal dystrophies from the 19th century to the present. Among 3076 registered cases, the primary diagnosis of generalized retinal dystrophy was assessed by chart review, including fundus photographs and electroretinograms. Demographic data on the Danish population were retrieved from Statistics Denmark...

Occult Macular Dystrophy

Directory of Open Access Journals (Sweden)

Işıl Sayman Muslubaş

2016-04-01

Full Text Available Occult macular dystrophy is an inherited macular dystrophy characterized by a progressive decline of bilateral visual acuity with normal fundus appearance, fluorescein angiogram and full-field electroretinogram. This case report presents a 20-year-old female patient with bilateral progressive decline of visual acuity for six years. Her visual acuity was 3-4/10 in both eyes. Anterior segment and fundus examination, fluorescein angiogram and full-field electroretinogram were normal. She could read all Ishihara pseudoisochromatic plates. Fundus autofluorescence imaging was normal. There was a mild central hyporeflectance on fundus infrared reflectance imaging in both eyes. Reduced foveal thickness and alterations of the photoreceptor inner and outer segment junction were observed by optical coherence tomography in both eyes. Central scotoma was also found by microperimetry and reduced central response was revealed by multifocal electroretinogram in both eyes. These findings are consistent with the clinical characteristics of occult macular dystrophy

Cardiac involvement in patients with limb-girdle muscular dystrophy type 2 and Becker muscular dystrophy

DEFF Research Database (Denmark)

Sveen, Marie-Louise; Thune, Jens Jakob; Køber, Lars

2008-01-01

OBJECTIVE: To investigate the extent of cardiac involvement in patients with 1 of the 12 groups of recessively inherited limb-girdle muscular dystrophy type 2 (LGMD2A-L) and Becker muscular dystrophy (BMD). DESIGN: Prospective screening. SETTING: Neuromuscular Clinic and Department of Cardiology...

Distrofia miotônica tipo 1 em pacientes com catarata: diagnóstico molecular para triagem e aconselhamento genético Myotonic dystrophy type 1 in cataract patients: Molecular diagnosis for screening and genetic counseling

Directory of Open Access Journals (Sweden)

María Verónica Muñoz Rojas

2005-02-01

Full Text Available OBJETIVOS: Detectar novos pacientes portadores da mutação e pré-mutação da DM1, entre pacientes com catarata e realizar aconselhamento genético. MÉTODOS: Foi estudado o DNA de 60 pacientes, por meio da análise por reação em cadeia de polimerase. Este estudo foi realizado no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto e os pacientes foram selecionados a partir dos atendimentos realizados no Ambulatório de Catarata do Departamento de Oftalmologia, entre 01/01/1982 a 30/06/1995. Os critérios de seleção foram pacientes com menos de 55 anos, com catarata bilateral, sem fator causal que justificasse a lesão, exceto por diabete melito tipo 2 com ou sem sinais neuromusculares sugestivos de distrofia miotônica. RESULTADOS: Foram encontrados 3 pacientes com a mutação completa, correspondendo a 5% da amostra. Nenhum portador da pré-mutação foi encontrado. A partir dos pacientes diagnosticados, outros familiares afetados foram detectados. CONCLUSÕES: Este estudo enfatiza a importância da triagem de distrofia miotônica tipo 1 (DM1 entre pacientes com catarata, e mostra, também, a importância do aconselhamento genético destes pacientes.PURPOSE: To detect MD1 premutation and full mutation carriers among cataract patients and offer familial genetic counseling. METHODS: We studied the DNA of 60 selected cataract patients through polymerase chain reaction analysis. This study was performed at the "Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto" where selected patients had been examined at the Cataract Outpatient Clinic from 01/01/1982 to 30/06/1995. Selection criteria were age under 55 with no obvious precipitating factor, except diabetes mellitus type 2, with or without neuromuscular signs suggestive of myotonic dystrophy. RESULTS: Three patients were found to have a full mutation corresponding to 5% of the group. Additional affected individuals were found among patients' relatives. No

Genetics Home Reference: cone-rod dystrophy

Science.gov (United States)

... common cause of autosomal recessive cone-rod dystrophy , accounting for 30 to 60 percent of cases. At ... dystrophy play essential roles in the structure and function of specialized light receptor cells (photoreceptors) in the ...

Infrastructure for Clinical Trials in Duchenne Dystrophy

Science.gov (United States)

2010-09-13

A Zimmerman, T Duong, J Florence and the CINRG Investigators. Pulmonary Function Characteristics of Boys with Duchenne and Becker Muscular Dystrophy ...designated CINRG site staff 1. Has the participant been clinically diagnosed with Limb-Girdle or Becker muscular dystrophy ? LGMD BMD 2. Was...Number: W81XWH-09-1-0592 TITLE: CINRG: Infrastructure for Clinical Trials in Duchenne Dystrophy PRINCIPAL INVESTIGATOR: Avital Cnaan, PhD

Muscular dystrophy

Science.gov (United States)

... are no known cures for the various muscular dystrophies. The goal of treatment is to control symptoms. Physical therapy may help maintain muscle strength and function. Leg braces and a wheelchair ...

Pattern analysis in MR imaging of muscle diseases

International Nuclear Information System (INIS)

Kaiser, W.A.; Schalke, B.C.G.

1987-01-01

Between March 1984 and March 1987, 161 patients with muscle diseases underwent MR imaging performed with a 1.0-T superconductive magnet. Forty-four had progressive muscular dystrophies, 25 had different types of myositis, 19 had spinal or neural muscular atrophies, 16 had myotonic dystrophy, 22 had metabolic disorders, and 35 had other muscle disease, including muscle tumors, posttraumatic muscular atrophies, and postradiation effects. The advantages of MR imaging are the high sensitivity and soft-tissue contrast, as well as the depiction of typical distribution patterns of affected muscle groups, which can be used in diagnosis, biopsy planning, and design of therapy

Muscular Dystrophy

Science.gov (United States)

... Surveillance Tracking and Research Network , known as MD STAR net . Learn more about CDC’s other muscular dystrophy ... for Disease Control and Prevention Email Recommend Tweet YouTube Instagram Listen Watch RSS ABOUT About CDC Jobs ...

Radiographic features of Golden Retriever muscular dystrophy.

Science.gov (United States)

Brumitt, Jason W; Essman, Stephanie C; Kornegay, Joe N; Graham, John P; Weber, William J; Berry, Clifford R

2006-01-01

Golden Retriever muscular dystrophy is an inherited, degenerative myopathy due to the absence of dystrophin and is used as a model of Duchenne muscular dystrophy of young boys. This report describes the radiographic abnormalities of Golden Retriever muscular dystrophy in 26 dogs. The thoracic abnormalities included diaphragmatic asymmetry (18/26), diaphragmatic undulation (18/26), and gastro-esophageal hiatal hernia (6/26). Pelvic abnormalities included narrowing of the body of the ilia (14/19), ventral deviation and curvature of the tuber ischii (14/19), elongation of the obturator foramen with a decrease in opacity of the surrounding bone (12/19), and lateral flaring of the wings of the ilia (12/19). Abdominal abnormalities consisted of hepatomegaly (14/22) and poor serosal detail (12/22). The unique thoracic abnormalities were a consistent finding in affected Golden Retriever muscular dystrophy dogs. The diagnosis of muscular dystrophy should be included in the differential list if the combination of diaphragm undulation and asymmetry, and gastro-esophageal hiatal hernia are identified. These diaphragmatic abnormalities are related to hypertrophy and hyperplasia of the diaphragm. Additionally, the skeletal changes of pelvic tilt, elongation of the pelvis, widening of the obturator foramina and thinning of the ischiatic tables appear to be specific to Golden Retriever muscular dystrophy in dogs. These pelvic abnormalities are most likely secondary to bone remodeling associated with the progressive skeletal myopathy and subsequent contracture/fibrosis.

Translational Research for Muscular Dystrophy

Science.gov (United States)

2012-05-01

muscle dystrophy with abnormal waddling gait at 4 weeks of age. At 10 weeks of age, double mutants exhibit skeletal muscle degeneration, necrosis... dystrophy (MCMD). Homozygous dyW mice are passive, small, and emaciated, and demonstrate partial hindleg weakness and clasping. Their muscles contain...was statistically significant for both single- treatment groups. Figure 4. Effect of GW and AICAR on body mass, muscle mass, and behavioral

What Are the Types of Muscular Dystrophy?

Science.gov (United States)

... muscular dystrophy? There are more than 30 forms of muscular dystrophy (MD), with information on the primary types included in the table below. 1 Duchenne (DMD) What It Is Common Symptoms How It ...

Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet): case definition in surveillance for childhood-onset Duchenne/Becker muscular dystrophy.

Science.gov (United States)

Mathews, Katherine D; Cunniff, Chris; Kantamneni, Jiji R; Ciafaloni, Emma; Miller, Timothy; Matthews, Dennis; Cwik, Valerie; Druschel, Charlotte; Miller, Lisa; Meaney, F John; Sladky, John; Romitti, Paul A

2010-09-01

The Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) is a multisite collaboration to determine the prevalence of childhood-onset Duchenne/Becker muscular dystrophy and to characterize health care and health outcomes in this population. MD STARnet uses medical record abstraction to identify patients with Duchenne/Becker muscular dystrophy born January 1, 1982 or later who resided in 1 of the participating sites. Critical diagnostic elements of each abstracted record are reviewed independently by >4 clinicians and assigned to 1 of 6 case definition categories (definite, probable, possible, asymptomatic, female, not Duchenne/Becker muscular dystrophy) by consensus. As of November 2009, 815 potential cases were reviewed. Of the cases included in analysis, 674 (82%) were either ''definite'' or ''probable'' Duchenne/Becker muscular dystrophy. These data reflect a change in diagnostic testing, as case assignment based on genetic testing increased from 67% in the oldest cohort (born 1982-1987) to 94% in the cohort born 2004 to 2009.

Mitochondrial disorders in progressive muscular dystrophies

Directory of Open Access Journals (Sweden)

D. A. Kharlamov

2014-01-01

Full Text Available The literature review gives data on the role of mitochondrial disorders in the pathogenesis of different progressive muscular dystrophies. It describes changes in Duchenne, limb-girdle, facial scapulohumeral (Landuzi—Degerina muscular dystrophies. The review is based on both clinical and experimental animal studies. Along with the implication of mitochondria in the pathogenesis of the diseases, it describes muscular dystrophy treatment options compensating for energy disorders and overcoming oxidative stress and mitochondrial dysfunction. Mitochondrial studies in different muscle diseases hand physicians treatment modalities that fail to lead to recovery, but compensate for disorders caused by mutations in the genetic apparatus. 

Becker muscular dystrophy: an unusual presentation.

OpenAIRE

Thakker, P B; Sharma, A

1993-01-01

A 15 year old boy who presented with passing painless dark urine was found to have myoglobinuria. His creatine phosphokinase was raised, and a muscle biopsy specimen showed non-specific dystrophic changes. Subsequent DNA analysis led to the diagnosis of Becker muscular dystrophy. Myoglobinuria may be a presenting symptom of Becker muscular dystrophy.

Resistance training in patients with limb-girdle and becker muscular dystrophies

DEFF Research Database (Denmark)

Sveen, Marie-Louise; Andersen, Søren P; Ingelsrud, Lina H

2013-01-01

In this study we investigated the effect of strength training in patients with limb-girdle muscular dystrophy (LGMD) and Becker muscular dystrophy (BMD).......In this study we investigated the effect of strength training in patients with limb-girdle muscular dystrophy (LGMD) and Becker muscular dystrophy (BMD)....

Respiratory function in facioscapulohumeral muscular dystrophy 1

NARCIS (Netherlands)

Wohlgemuth, M.; Horlings, G.C.; Kooi, E.L. van der; Gilhuis, H.J.; Hendriks, J.C.M.; Maarel, S.M. van der; Engelen, B.G.M. van; Heijdra, Y.F.; Padberg, G.W.A.M.

2017-01-01

To test the hypothesis that wheelchair dependency and (kypho-)scoliosis are risk factors for developing respiratory insufficiency in facioscapulohumeral muscular dystrophy, we examined 81 patients with facioscapulohumeral muscular dystrophy 1 of varying degrees of severity ranging from ambulatory

Genetic modifiers of Duchenne and facioscapulohumeral muscular dystrophies.

Science.gov (United States)

Hightower, Rylie M; Alexander, Matthew S

2018-01-01

Muscular dystrophy is defined as the progressive wasting of skeletal muscles that is caused by inherited or spontaneous genetic mutations. Next-generation sequencing has greatly improved the accuracy and speed of diagnosis for different types of muscular dystrophy. Advancements in depth of coverage, convenience, and overall reduced cost have led to the identification of genetic modifiers that are responsible for phenotypic variability in affected patients. These genetic modifiers have been postulated to explain key differences in disease phenotypes, including age of loss of ambulation, steroid responsiveness, and the presence or absence of cardiac defects in patients with the same form of muscular dystrophy. This review highlights recent findings on genetic modifiers of Duchenne and facioscapulohumeral muscular dystrophies based on animal and clinical studies. These genetic modifiers hold great promise to be developed into novel therapeutic targets for the treatment of muscular dystrophies. Muscle Nerve 57: 6-15, 2018. © 2017 Wiley Periodicals, Inc.

Morphologic imaging in muscular dystrophies and inflammatory myopathies

International Nuclear Information System (INIS)

Degardin, Adrian; Lacour, Arnaud; Vermersch, Patrick; Morillon, David; Cotten, Anne; Stojkovic, Tanya

2010-01-01

To determine if magnetic resonance imaging (MR imaging) is useful in the diagnostic workup of muscular dystrophies and idiopathic inflammatory myopathies for describing the topography of muscle involvement. MR imaging was performed in 31 patients: 8 with dystrophic myotony types 1 (n = 4) or 2 (n = 4); 11 with limb-girdle muscular dystrophy, including dysferlinopathy, calpainopathy, sarcoglycanopathy, and dystrophy associated with fukutin-related protein mutation; 3 with Becker muscular dystrophy; and 9 with idiopathic inflammatory myopathies, including polymyositis, dermatomyositis, and sporadic inclusion body myositis. Analysis of T1 images enabled us to describe the most affected muscles and the muscles usually spared for each muscular disease. In particular, examination of pelvis, thigh, and leg muscles demonstrated significant differences between the muscular diseases. On STIR images, hyperintensities were present in 62% of our patients with muscular dystrophies. A specific pattern of muscular involvement was established for each muscular disease. Hyperintensities observed on STIR images precede fatty degeneration and are not specific for inflammatory myopathies. (orig.)

Morphologic imaging in muscular dystrophies and inflammatory myopathies

Energy Technology Data Exchange (ETDEWEB)

Degardin, Adrian; Lacour, Arnaud; Vermersch, Patrick [CHU de Lille, Clinique neurologique, Lille (France); Morillon, David; Cotten, Anne [CHRU de Lille, Service de Radiologie Osteoarticulaire, Hopital Roger Salengro, Lille (France); Stojkovic, Tanya [G-H Pitie-Salpetriere, Institut de Myologie, Paris (France)

2010-12-15

To determine if magnetic resonance imaging (MR imaging) is useful in the diagnostic workup of muscular dystrophies and idiopathic inflammatory myopathies for describing the topography of muscle involvement. MR imaging was performed in 31 patients: 8 with dystrophic myotony types 1 (n = 4) or 2 (n = 4); 11 with limb-girdle muscular dystrophy, including dysferlinopathy, calpainopathy, sarcoglycanopathy, and dystrophy associated with fukutin-related protein mutation; 3 with Becker muscular dystrophy; and 9 with idiopathic inflammatory myopathies, including polymyositis, dermatomyositis, and sporadic inclusion body myositis. Analysis of T1 images enabled us to describe the most affected muscles and the muscles usually spared for each muscular disease. In particular, examination of pelvis, thigh, and leg muscles demonstrated significant differences between the muscular diseases. On STIR images, hyperintensities were present in 62% of our patients with muscular dystrophies. A specific pattern of muscular involvement was established for each muscular disease. Hyperintensities observed on STIR images precede fatty degeneration and are not specific for inflammatory myopathies. (orig.)

CINRG: Infrastructure for Clinical Trials in Duchenne Dystrophy

Science.gov (United States)

2013-09-01

monitoring visit to monitor this study, the PITT0908 clinical trial, a study on facioscapulohumeral muscular dystrophy (FSHD), and PITT0112 Becker natural...height findings manuscript are currently in working stage and circulating among co-authors for editing. 2.3.6 Becker Muscular Dystrophy – A Natural...participants with Becker muscular dystrophy . The study period is 36 months per patient. This project is primarily funded by the National Institutes of

Application of FTA sample collection and DNA purification system on the determination of CTG trinucleotide repeat size by PCR-based Southern blotting.

Science.gov (United States)

Hsiao, K M; Lin, H M; Pan, H; Li, T C; Chen, S S; Jou, S B; Chiu, Y L; Wu, M F; Lin, C C; Li, S Y

1999-01-01

Myotonic dystrophy (DM) is caused by a CTG trinucleotide expansion mutation at exon 15 of the myotonic dystrophy protein kinase gene. The clinical severity of this disease correlates with the length of the CTG trinucleotide repeats. Determination of the CTG repeat length has been primarily relied on by Southern blot analysis of restriction enzyme-digested genomic DNA. The development of PCR-based Southern blotting methodology provides a much more sensitive and simpler protocol for DM diagnosis. However, the quality of the template and the high (G+C) ratio of the amplified region hamper the use of PCR on the diagnosis of DM. A modified PCR protocol to amplify different lengths of CTG repeat region using various concentrations of 7deaza-dGTP has been reported (1). Here we describe a procedure including sample collection, DNA purification, and PCR analysis of CTG repeat length without using 7-deaza-dGTP. This protocol is very sensitive and convenient because only a small number of nucleate cells are needed for detection of CTG expansion. Therefore, it could be very useful in clinical and prenatal diagnosis as well as in prevalence study of DM.

Associação familiar de miastenia grave e síndrome miotônica Familial association of myasthenia gravis and myotonic syndrome

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Sylvio Saraiva

1969-12-01

Full Text Available É relatada uma associação familiar incomum, incidindo em mãe e filha, a primeira com síndrome miotônica e, a segunda, com miastenia grave, forma ocular. Um terceiro membro da família, irmão da paciente com miotonia, teria também manifestações dessa síndrome. São comentados aspectos clínico-laboratoriais dos casos estudados.An uncommon association of myasthenia gravis in a child and a myotonic syndrome in her mother is reported. A brother of the second patient probably had myotonic symptomatology. Clinical and laboratorial aspects are discussed.

Human muscle proteins: analysis by two-dimensional electrophoresis

Energy Technology Data Exchange (ETDEWEB)

Giometti, C.S.; Danon, M.J.; Anderson, N.G.

1983-09-01

Proteins from single frozen sections of human muscle were separated by two-dimensional gel electrophoresis and detected by fluorography or Coomassie Blue staining. The major proteins were identical in different normal muscles obtained from either sex at different ages, and in Duchenne and myotonic dystrophy samples. Congenital myopathy denervation atrophy, polymyositis, and Becker's muscular dystrophy samples, however, showed abnormal myosin light chain compositions, some with a decrease of fast-fiber myosin light chains and others with a decrease of slow-fiber light chains. These protein alterations did not correlate with any specific disease, and may be cause by generalized muscle-fiber damage.

Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in the Netherlands : a cohort study

NARCIS (Netherlands)

Hoogerwaard, EM; Bakker, E; Ippel, PF; Oosterwijk, JC; Majoor-Krakauer, DF; Leschot, NJ; Van Essen, AJ; Brunner, HG; van der Wouw, PA; Wilde, AAM; de Visser, Marianne

1999-01-01

Background Carriers of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) may show muscle weakness or dilated cardiomyopathy. Studies focusing on skeletal-muscle involvement were done before DNA analysis was possible. We undertook a cross-sectional study in a population of

Signs and symptoms of Duchenne muscular dystrophy and Becker muscular dystrophy among carriers in The Netherlands: a cohort study

NARCIS (Netherlands)

Hoogerwaard, E. M.; Bakker, E.; Ippel, P. F.; Oosterwijk, J. C.; Majoor-Krakauer, D. F.; Leschot, N. J.; van Essen, A. J.; Brunner, H. G.; van der Wouw, P. A.; Wilde, A. A.; de Visser, M.

1999-01-01

BACKGROUND: Carriers of Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) may show muscle weakness or dilated cardiomyopathy. Studies focusing on skeletal-muscle involvement were done before DNA analysis was possible. We undertook a cross-sectional study in a population of

Muscular Dystrophy

Science.gov (United States)

... sets of muscles and cause different degrees of muscle weakness. Duchenne muscular dystrophy is the most common and the most severe ... can walk independently. Prednisone If a child has Duchenne muscular ... to help slow the rate of muscle deterioration. By doing so, the child may be ...

Muscular Dystrophy (MD)

Science.gov (United States)

... patients may need assisted ventilation to treat respiratory muscle weakness and a pacemaker for cardiac abnormalities. View Full Treatment Information Definition The muscular dystrophies (MD) are a group of more than 30 ...

Genetics Home Reference: autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy

Science.gov (United States)

... Facebook Twitter Home Health Conditions APECED Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy Printable PDF Open All Close All ... view the expand/collapse boxes. Description Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy ( APECED ) is an inherited condition that ...

Prevalence of muscular dystrophy in patients with muscular disorders in Tehran, Iran

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Khadijeh Hajinaghi Tehrani

2018-05-01

Full Text Available Muscular dystrophy is a group of diseases that is characterized by progressive muscle wasting and the weakness of variable distribution and severity. On the basis of the distribution of predominant muscle weakness, there are many different kinds of muscular dystrophy. Some dystrophies are especially frequent in certain populations. There are no studies on the prevalence of muscular dystrophy in Iran. This study was aimed to survey the prevalence of muscular dystrophy among Iranian patients with muscular disorders. This analytical cross-sectional study was conducted on 1000 patients with musculoskeletal disorders who visited the dystrophy association of Bou-Ali Hospital (Tehran from June 2014 to June 2016. Patients’ data were extracted using a checklist that included age, gender, age of onset, family history, findings from clinical diagnostic tests and types of muscular dystrophy. The clinical findings were the results of genetic tests; EMG-NCV; para-clinical findings, including LDH and CPK; and pathological findings. All data were analyzed by SPSS V.22 (IBM Inc., NY with Chi Square and One way ANOVA tests. All analyses were performed with P = 0.05 considered as the threshold of statistical significant. Out of the 337 patients studied, 262 (77.7% were male and 75 (22.3% were female. Subjects had a mean (± SD age of 26.08 (± 11.86 years with an age range of 3 to 59 years. The most common types of muscular dystrophy were found to be Duchenne dystrophy (131 cases, 38.9%, limb-girdle dystrophy (91 cases, 27%, Becker dystrophy (58 cases, 17.2%, FSHD dystrophy (31 cases, 9.2%, and SMA (26 cases, 7.7%, respectively. The results showed that a statistically significant relationship between dystrophy types and gender, age, family history, age of diagnosis, CPK and LDH levels (P < 0.001. There were no statistical relationship between dystrophy types and pathological findings (P = 0.57, EMG-NCV test results (P = 0.062, and genetic findings (P = 0

Crystalline Subtype of Pre-Descemetic Corneal Dystrophy

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Rosa Dolz-Marco

2014-01-01

Full Text Available Purpose: To report corneal findings in a familial case of the crystalline subtype of pre- Descemetic corneal dystrophy. Case Report: A 19-year-old girl and her 44-year-old mother were found to have asymptomatic, bilateral, punctiform and multi-colored crystalline opacities across the whole posterior layer of the corneas. Endothelial specular microscopy revealed the presence of white round flecks located at different levels anterior to the endothelium. No systemic abnormalities or medications could be related to account for these findings. Conclusion: To the best of our knowledge, this is the third familial report of this rare corneal disorder. Differential diagnosis may include Schnyder corneal dystrophy, cystinosis, Bietti΄s dystrophy and monoclonal gammopathy.

Crystalline Subtype of Pre-Descemetic Corneal Dystrophy

Science.gov (United States)

Dolz-Marco, Rosa; Gallego-Pinazo, Roberto; Pinazo-Durán, María Dolores; Díaz-Llopis, Manuel

2014-01-01

Purpose To report corneal findings in a familial case of the crystalline subtype of pre-Descemetic corneal dystrophy. Case Report A 19-year-old girl and her 44-year-old mother were found to have asymptomatic, bilateral, punctiform and multi-colored crystalline opacities across the whole posterior layer of the corneas. Endothelial specular microscopy revealed the presence of white round flecks located at different levels anterior to the endothelium. No systemic abnormalities or medications could be related to account for these findings. Conclusion To the best of our knowledge, this is the third familial report of this rare corneal disorder. Differential diagnosis may include Schnyder corneal dystrophy, cystinosis, Bietti´s dystrophy and monoclonal gammopathy. PMID:25279130

Facioscapulohumeral muscular dystrophy

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... There is no known cure for facioscapulohumeral muscular dystrophy. Treatments are given to control symptoms and improve quality of life. Activity is encouraged. Inactivity such as bedrest can make the muscle disease worse. Physical therapy may help maintain muscle ...

Central areolar choroidal dystrophy with associated dominant drusen

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Julie Rodman

2013-04-01

Conclusion: Central areolar choroidal dystrophy normally presents without drusen. However, in patients manifesting a specific mutation, central areolar choridal dystrophy may present in conjunction with drusen. It appears that the Arg142Trp mutation is one of the factors predisposing to drusen formation.

Cognitive and Neurobehavioral Profile in Boys With Duchenne Muscular Dystrophy.

Science.gov (United States)

Banihani, Rudaina; Smile, Sharon; Yoon, Grace; Dupuis, Annie; Mosleh, Maureen; Snider, Andrea; McAdam, Laura

2015-10-01

Duchenne muscular dystrophy is a progressive neuromuscular condition that has a high rate of cognitive and learning disabilities as well as neurobehavioral disorders, some of which have been associated with disruption of dystrophin isoforms. Retrospective cohort of 59 boys investigated the cognitive and neurobehavioral profile of boys with Duchenne muscular dystrophy. Full-scale IQ of Duchenne muscular dystrophy. © The Author(s) 2015.

Cone rod dystrophies

Science.gov (United States)

Hamel, Christian P

2007-01-01

Cone rod dystrophies (CRDs) (prevalence 1/40,000) are inherited retinal dystrophies that belong to the group of pigmentary retinopathies. CRDs are characterized by retinal pigment deposits visible on fundus examination, predominantly localized to the macular region. In contrast to typical retinitis pigmentosa (RP), also called the rod cone dystrophies (RCDs) resulting from the primary loss in rod photoreceptors and later followed by the secondary loss in cone photoreceptors, CRDs reflect the opposite sequence of events. CRD is characterized by primary cone involvement, or, sometimes, by concomitant loss of both cones and rods that explains the predominant symptoms of CRDs: decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The clinical course of CRDs is generally more severe and rapid than that of RCDs, leading to earlier legal blindness and disability. At end stage, however, CRDs do not differ from RCDs. CRDs are most frequently non syndromic, but they may also be part of several syndromes, such as Bardet Biedl syndrome and Spinocerebellar Ataxia Type 7 (SCA7). Non syndromic CRDs are genetically heterogeneous (ten cloned genes and three loci have been identified so far). The four major causative genes involved in the pathogenesis of CRDs are ABCA4 (which causes Stargardt disease and also 30 to 60% of autosomal recessive CRDs), CRX and GUCY2D (which are responsible for many reported cases of autosomal dominant CRDs), and RPGR (which causes about 2/3 of X-linked RP and also an undetermined percentage of X-linked CRDs). It is likely that highly deleterious mutations in genes that otherwise cause RP or macular dystrophy may also lead to CRDs. The diagnosis of CRDs is based on clinical history, fundus examination and electroretinogram. Molecular diagnosis can be made for some genes, genetic counseling is always advised. Currently

Cone rod dystrophies

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Hamel Christian P

2007-02-01

Full Text Available Abstract Cone rod dystrophies (CRDs (prevalence 1/40,000 are inherited retinal dystrophies that belong to the group of pigmentary retinopathies. CRDs are characterized by retinal pigment deposits visible on fundus examination, predominantly localized to the macular region. In contrast to typical retinitis pigmentosa (RP, also called the rod cone dystrophies (RCDs resulting from the primary loss in rod photoreceptors and later followed by the secondary loss in cone photoreceptors, CRDs reflect the opposite sequence of events. CRD is characterized by primary cone involvement, or, sometimes, by concomitant loss of both cones and rods that explains the predominant symptoms of CRDs: decreased visual acuity, color vision defects, photoaversion and decreased sensitivity in the central visual field, later followed by progressive loss in peripheral vision and night blindness. The clinical course of CRDs is generally more severe and rapid than that of RCDs, leading to earlier legal blindness and disability. At end stage, however, CRDs do not differ from RCDs. CRDs are most frequently non syndromic, but they may also be part of several syndromes, such as Bardet Biedl syndrome and Spinocerebellar Ataxia Type 7 (SCA7. Non syndromic CRDs are genetically heterogeneous (ten cloned genes and three loci have been identified so far. The four major causative genes involved in the pathogenesis of CRDs are ABCA4 (which causes Stargardt disease and also 30 to 60% of autosomal recessive CRDs, CRX and GUCY2D (which are responsible for many reported cases of autosomal dominant CRDs, and RPGR (which causes about 2/3 of X-linked RP and also an undetermined percentage of X-linked CRDs. It is likely that highly deleterious mutations in genes that otherwise cause RP or macular dystrophy may also lead to CRDs. The diagnosis of CRDs is based on clinical history, fundus examination and electroretinogram. Molecular diagnosis can be made for some genes, genetic counseling is

Posterior amorphous corneal dystrophy: case report

OpenAIRE

Oliveira, Lauro Augusto de [UNIFESP; Vieira, Luiz Antônio [UNIFESP; Freitas, Denise de [UNIFESP; Sousa, Luciene Barbosa de [UNIFESP

2006-01-01

O objetivo deste trabalho é alertar o oftalmologista da possibilidade de se deparar com casos raros de distrofias corneanas. Neste caso correlacionamos os achados clínicos da distrofia amorfa posterior com refração, topografia e biomicroscopia ultra-sônica.The purpose of this paper is to warn the ophthalmologist about the possibility of facing rare cases of corneal dystrophies. Clinical findings of a case of posterior amorphous dystrophy were correlated with refraction, topography, and ultras...

Stem cell transplantation for treating Duchenne muscular dystrophy

Science.gov (United States)

Yang, Xiaofeng

2012-01-01

OBJECTIVE: To identify global research trends in stem cell transplantation for treating Duchenne muscular dystrophy using a bibliometric analysis of Web of Science. DATA RETRIEVAL: We performed a bibliometric analysis of studies on stem cell transplantation for treating Duchenne muscular dystrophy from 2002 to 2011 retrieved from Web of Science. SELECTION CRITERIA: Inclusion criteria: (a) peer-reviewed published articles on stem cell transplantation for treating Duchenne muscular dystrophy indexed in Web of Science; (b) original research articles, reviews, meeting abstracts, proceedings papers, book chapters, editorial material, and news items; and (c) publication between 2002 and 2011. Exclusion criteria: (a) articles that required manual searching or telephone access; (b) documents that were not published in the public domain; and (c) corrected papers. MAIN OUTCOME MEASURES: (1) Annual publication output; (2) distribution according to subject areas; (3) distribution according to journals; (4) distribution according to country; (5) distribution according to institution; (6) distribution according to institution in China; (7) distribution according to institution that cooperated with Chinese institutions; (8) top-cited articles from 2002 to 2006; (9) top-cited articles from 2007 to 2011. RESULTS: A total of 318 publications on stem cell transplantation for treating Duchenne muscular dystrophy were retrieved from Web of Science from 2002 to 2011, of which almost half derived from American authors and institutes. The number of publications has gradually increased over the past 10 years. Most papers appeared in journals with a focus on gene and molecular research, such as Molecular Therapy, Neuromuscular Disorders, and PLoS One. The 10 most-cited papers from 2002 to 2006 were mostly about different kinds of stem cell transplantation for muscle regeneration, while the 10 most-cited papers from 2007 to 2011 were mostly about new techniques of stem cell transplantation

Preimplantation genetic diagnosis associated to Duchenne muscular dystrophy.

Science.gov (United States)

Bianco, Bianca; Christofolini, Denise Maria; Conceição, Gabriel Seixas; Barbosa, Caio Parente

2017-01-01

Duchenne muscular dystrophy is the most common muscle disease found in male children. Currently, there is no effective therapy available for Duchenne muscular dystrophy patients. Therefore, it is essential to make a prenatal diagnosis and provide genetic counseling to reduce the birth of such boys. We report a case of preimplantation genetic diagnosis associated with Duchenne muscular dystrophy. The couple E.P.R., 38-year-old, symptomatic patient heterozygous for a 2 to 47 exon deletion mutation in DMD gene and G.T.S., 39-year-old, sought genetic counseling about preimplantation genetic diagnosis process. They have had a 6-year-old son who died due to Duchenne muscular dystrophy complications. The couple underwent four cycles of intracytoplasmic sperm injection (ICSI) and eight embryos biopsies were analyzed by polymerase chain reaction (PCR) for specific mutation analysis, followed by microarray-based comparative genomic hybridisation (array CGH) for aneuploidy analysis. Preimplantation genetic diagnosis revealed that two embryos had inherited the maternal DMD gene mutation, one embryo had a chromosomal alteration and five embryos were normal. One blastocyst was transferred and resulted in successful pregnancy. The other embryos remain vitrified. We concluded that embryo analysis using associated techniques of PCR and array CGH seems to be safe for embryo selection in cases of X-linked disorders, such as Duchenne muscular dystrophy.

Median nail dystrophy involving the thumb nail

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Rahulkrishna Kota

2016-01-01

Full Text Available Median canaliform dystrophy of Heller is a rare entity characterized by a midline or a paramedian ridge or split and canal formation in nail plate of one or both the thumb nails. It is an acquired condition resulting from a temporary defect in the matrix that interferes with nail formation. Habitual picking of the nail base may be responsible for some cases. Histopathology classically shows parakeratosis, accumulation of melanin within and between the nail bed keratinocytes. Treatment of median nail dystrophy includes injectable triamcinalone acetonide, topical 0.1% tacrolimus, and tazarotene 0.05%, which is many a times challenging for a dermatologist. Psychiatric opinion should be taken when associated with the depressive, obsessive-compulsive, or impulse-control disorder. We report a case of 19-year-old male diagnosed as median nail dystrophy.

ONR Tokyo Scientific Bulletin. Volume 4, Number 4, October-December 1979,

Science.gov (United States)

1979-12-01

myotonic dystrophy, myxeodema, obesity , Parkinson’s disease, epilepsy, alcoholism, schizophrenia, rheumatoid arthritis, tetanus, acromegaly, depression...12 12 Iraq 2,000 8 7 Korea 2,000 84 26 Malaysia 3,000 5 5 Phillipines 5,000 18 10 Singapore 1,000 2 2 Sri Lanka 7,000 7 7 Thailand 2,000 18 10...previously in the Bulletin. MALAYSIA Chemistry research in Malaysian universities is mainly in the areas of applications such as natural products

Further delineation of spondylometaphyseal dysplasia with cone-rod dystrophy

NARCIS (Netherlands)

Sousa, Sérgio B.; Russell-Eggitt, Isabelle; Hall, Christine; Hall, Bryan D.; Hennekam, Raoul C. M.

2008-01-01

There are several entities that combine a skeletal dysplasia with a retinal dystrophy. Recently, another possibly autosomal recessive entity was added to this group characterized by a specific spondylometaphyseal dysplasia and a cone-rod dystrophy, without other significant impairments. The entity

[Posterior polymorphous dystrophy, case report and literature review].

Science.gov (United States)

Mendoza-Adam, G; Hernandez-Camarena, J C; Valdez-García, J E

2015-09-01

Posterior Polymorphous Dystrophy (DPP) is a rare posterior corneal dystrophy that is genetically transmitted as autosomal dominant. Corneal structures affected in this dystrophy are Descemet membrane and the endothelium. A case is presented on a 47 years old woman with no relevant history, with typical findings of DPP (vesicular and band lesions at the endothelium and posterior Descemet). To our knowledge there are no reported cases of DPP in Latin-American patients in the literature. The clinical manifestations in our patient were found to be very similar to the cases reported in other populations. Copyright © 2014 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

An experimental study of BIGH3 gene mutations in the patients with corneal dystrophies

International Nuclear Information System (INIS)

Jin Tao; Zou Liuhe; Yang Ling

2004-01-01

Objective: To evaluate BIGH3 gene mutations in Chinese patents with corneal dystrophies. Methods: 2ml peripheral venous blood was collected from 15 patients with granular corneal dystrophies and 5 normal subjects. Leucocytes DNA was extracted with standard method. With two pairs of oligonucleotide primers, exon 4 and exon 12 of the BIGH3 gene were amplified using the polymerase chain reaction. Amplified DNA fragments were purified and sequenced directly. Results: Mutations in BIGH3 gene were detected in all the patients with corneal dystrophies. BIGH3 gene mutations were not found in normal subjects. 12 patients with Avellino corneal dystrophy had the missense mutation R124H in the BIGH3 gene. 3 patients with granular corneal dystrophy had the missense mutation R555W in the BIGH3 gene. Conclusion: R124H and R555W mutations in BIGH3 gene were also found in the Chinese patients with Avellino and granular corneal dystrophies. In China, Avellino corneal dystrophy associated with the R124H mutation is the most common form in the corneal dystrophies resulted by BIGH3 gene mutions. Condon 124 and 555 are also the hot spots for the mutations in the BIGH3 gene in the Chinese patients with corneal dystrophies. Molecular genetic analysis may be repuired for proper diagnosis and subclassification of corneal dystrophies. (authors)

Upper limb function in adults with Duchenne muscular dystrophy

NARCIS (Netherlands)

B. Bartels (Bart); R.F. Pangalila (Robert); M.P. Bergen (Michael); N.A.M. Cobben (Nicolle); H.J. Stam (Henk); M.E. Roebroeck (Marij)

2011-01-01

textabstractTo determine upper limb function and associated factors in adults with Duchenne muscular dystrophy. Design: Cross-sectional study. Subjects: A sample of 70 men with Duchenne muscular dystrophy (age range 20-43 years). Methods: General motor function and, in particular, upper limb distal

Guidelines for the Perianesthesia Care of the Duchenne Muscular Dystrophy/Becker Muscular Dystrophy Patient.

Science.gov (United States)

Alliod, Barbara A; Ash, Rebecca A

2016-12-01

More patients suffering with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are presenting to perianesthesia settings for emergent and nonemergent treatment and care. A group of collaborative health care providers at Rush University Medical Center in Chicago developed a multidisciplinary DMD/BMD Task Force to study this disorder and create a set of guidelines to aid those engaging in the planning, execution of care, and recovery of this unique population in the perianesthesia setting. Attention to detail, well-executed preplanning, meticulous awareness of the patient, and prearranged implementation and intervention has proven to offset potential problems and complications and is the key to a successful perianesthesia period. Copyright © 2016 American Society of PeriAnesthesia Nurses. Published by Elsevier Inc. All rights reserved.

Duchenne muscular dystrophy: the management of scoliosis

Science.gov (United States)

Gardner, Adrian C.; Roper, Helen P.; Chikermane, Ashish A.; Tatman, Andrew J.

2016-01-01

This study summaries the current management of scoliosis in patients with Duchenne Muscular Dystrophy. A literature review of Medline was performed and the collected articles critically appraised. This literature is discussed to give an overview of the current management of scoliosis within Duchenne Muscular Dystrophy. Importantly, improvements in respiratory care, the use of steroids and improving surgical techniques have allowed patients to maintain quality of life and improved life expectancy in this patient group. PMID:27757431

Muscle protein analysis. II. Two-dimensional electrophoresis of normal and diseased human skeletal muscle

Energy Technology Data Exchange (ETDEWEB)

Giometti, C.S. (Argonne National Lab., IL); Barany, M.; Danon, M.J.; Anderson, N.G.

1980-07-01

High-resolution two-dimensional electrophoresis was used to analyze the major proteins of normal and pathological human-muscle samples. The normal human-muscle pattern contains four myosin light chains: three that co-migrate with the myosin light chains from rabbit fast muscle (extensor digitorum longus), and one that co-migrates with the light chain 2 from rabbit slow muscle (soleus). Of seven Duchenne muscular dystrophy samples, four yielded patterns with decreased amounts of actin and myosin relative to normal muscle, while three samples gave patterns comparable to that for normal muscle. Six samples from patients with myotonic dystrophy also gave normal patterns. In nemaline rod myopathy, in contrast, the pattern was deficient in two of the fast-type myosin light chains.

MR imaging of muscle diseases

International Nuclear Information System (INIS)

Kaiser, W.A.; Zeitler, E.; Schalke, B.C.G.

1986-01-01

Because of high soft-tissue contrast, MR imaging is especially suitable for the investigation of muscle diseases. Between March 1984 and March 1986, 76 patients with different types of muscle diseases were examined using a 1-T superconductive magnet (Siemens Magnetom). Studied were 14 patients with progressive muscular dystrophy (including carriers), 32 patients with myositis, four patients with myotonic dystrophy, six patients with spinal muscular atrophy, and 20 patients with other muscle diseases, including metabolic disorders. MR imaging showed typical signal patterns in affected muscle groups. These patterns can be used in the differential diagnosis, in biopsy planning, or in evaluation of response to therapy. The T1/T2 ratio especially seems to indicate very early stages of muscle disease

Neurocognitive Profiles in Duchenne Muscular Dystrophy and Gene Mutation Site

Science.gov (United States)

D’Angelo, Maria Grazia; Lorusso, Maria Luisa; Civati, Federica; Comi, Giacomo Pietro; Magri, Francesca; Del Bo, Roberto; Guglieri, Michela; Molteni, Massimo; Turconi, Anna Carla; Bresolin, Nereo

2011-01-01

The presence of nonprogressive cognitive impairment is recognized as a common feature in a substantial proportion of patients with Duchenne muscular dystrophy. To investigate the possible role of mutations along the dystrophin gene affecting different brain dystrophin isoforms and specific cognitive profiles, 42 school-age children affected with Duchenne muscular dystrophy, subdivided according to sites of mutations along the dystrophin gene, underwent a battery of tests tapping a wide range of intellectual, linguistic, and neuropsychologic functions. Full-scale intelligence quotient was approximately 1 S.D. below the population average in the whole group of dystrophic children. Patients with Duchenne muscular dystrophy and mutations located in the distal portion of the dystrophin gene (involving the 140-kDa brain protein isoform, called Dp140) were generally more severely affected and expressed different patterns of strengths and impairments, compared with patients with Duchenne muscular dystrophy and mutations located in the proximal portion of the dystrophin gene (not involving Dp140). Patients with Duchenne muscular dystrophy and distal mutations demonstrated specific impairments in visuospatial functions and visual memory (which seemed intact in proximally mutated patients) and greater impairment in syntactic processing. PMID:22000308

MR imaging of fukuyama congenital muscular dystrophy; a case report

International Nuclear Information System (INIS)

Yoo, Jeong Hyun; Kim, Yoo Kyung; Koo, Hae Soo; Park, Ki Deuk

2000-01-01

Fukuyama congenital muscular dystrophy is a genetic disease and common in Japan. The typical clinical features are hypotonia with an early infantile onset and severe developmental delay. The diagnosis is based on pathologic evidence of muscular dystrophy revealed by biopsy or an increased serum creatine kinase levels. Involvement of the brain is characterized by abnormal cerebral cortical dysplasia, cerebellar dysplasia, and white matter changes. We encountered a case of Fukuyama congenital muscular dystrophy in which brain MRI findings were typical, and present this case together with a review of the literature

Development of Non-Hormonal Steroids for the Treatment of Duchenne Muscular Dystrophy

Science.gov (United States)

2013-02-01

constructs envisioned in gene therapy, are also expressed in Becker muscular dystrophy (alleles of dystrophinopathy leading to milder disease). In other words...the Treatment of Duchenne Muscular Dystrophy PRINCIPAL INVESTIGATOR: Terence Partridge, PhD CONTRACTING ORGANIZATION: Children’s...Duchenne Muscular Dystrophy 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0754 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Terence Partridge

Dystrophin quantification and clinical correlations in Becker muscular dystrophy: implications for clinical trials.

Science.gov (United States)

Anthony, Karen; Cirak, Sebahattin; Torelli, Silvia; Tasca, Giorgio; Feng, Lucy; Arechavala-Gomeza, Virginia; Armaroli, Annarita; Guglieri, Michela; Straathof, Chiara S; Verschuuren, Jan J; Aartsma-Rus, Annemieke; Helderman-van den Enden, Paula; Bushby, Katherine; Straub, Volker; Sewry, Caroline; Ferlini, Alessandra; Ricci, Enzo; Morgan, Jennifer E; Muntoni, Francesco

2011-12-01

Duchenne muscular dystrophy is caused by mutations in the DMD gene that disrupt the open reading frame and prevent the full translation of its protein product, dystrophin. Restoration of the open reading frame and dystrophin production can be achieved by exon skipping using antisense oligonucleotides targeted to splicing elements. This approach aims to transform the Duchenne muscular dystrophy phenotype to that of the milder disorder, Becker muscular dystrophy, typically caused by in-frame dystrophin deletions that allow the production of an internally deleted but partially functional dystrophin. There is ongoing debate regarding the functional properties of the different internally deleted dystrophins produced by exon skipping for different mutations; more insight would be valuable to improve and better predict the outcome of exon skipping clinical trials. To this end, we have characterized the clinical phenotype of 17 patients with Becker muscular dystrophy harbouring in-frame deletions relevant to on-going or planned exon skipping clinical trials for Duchenne muscular dystrophy and correlated it to the levels of dystrophin, and dystrophin-associated protein expression. The cohort of 17 patients, selected exclusively on the basis of their genotype, included 4 asymptomatic, 12 mild and 1 severe patient. All patients had dystrophin levels of >40% of control and significantly higher dystrophin (P = 0.013), β-dystroglycan (P = 0.025) and neuronal nitric oxide synthase (P = 0.034) expression was observed in asymptomatic individuals versus symptomatic patients with Becker muscular dystrophy. Furthermore, grouping the patients by deletion, patients with Becker muscular dystrophy with deletions with an end-point of exon 51 (the skipping of which could rescue the largest group of Duchenne muscular dystrophy deletions) showed significantly higher dystrophin levels (P = 0.034) than those with deletions ending with exon 53. This is the first quantitative study on both

Dasatinib as a treatment for Duchenne muscular dystrophy.

Science.gov (United States)

Lipscomb, Leanne; Piggott, Robert W; Emmerson, Tracy; Winder, Steve J

2016-01-15

Identification of a systemically acting and universal small molecule therapy for Duchenne muscular dystrophy would be an enormous advance for this condition. Based on evidence gained from studies on mouse genetic models, we have identified tyrosine phosphorylation and degradation of β-dystroglycan as a key event in the aetiology of Duchenne muscular dystrophy. Thus, preventing tyrosine phosphorylation and degradation of β-dystroglycan presents itself as a potential therapeutic strategy. Using the dystrophic sapje zebrafish, we have investigated the use of tyrosine kinase and other inhibitors to treat the dystrophic symptoms in this model of Duchenne muscular dystrophy. Dasatinib, a potent and specific Src tyrosine kinase inhibitor, was found to decrease the levels of β-dystroglycan phosphorylation on tyrosine and to increase the relative levels of non-phosphorylated β-dystroglycan in sapje zebrafish. Furthermore, dasatinib treatment resulted in the improved physical appearance of the sapje zebrafish musculature and increased swimming ability as measured by both duration and distance of swimming of dasatinib-treated fish compared with control animals. These data suggest great promise for pharmacological agents that prevent the phosphorylation of β-dystroglycan on tyrosine and subsequent steps in the degradation pathway as therapeutic targets for the treatment of Duchenne muscular dystrophy. © The Author 2015. Published by Oxford University Press.

Prevalence of cardiomyopathy in duchenne and becker's muscular dystrophy

International Nuclear Information System (INIS)

Sultan, A.; Fayaz, M.

2008-01-01

Cardiac assessment was not done routinely in Duchenne (DMD) and Becker muscular dystrophy (BMD) patients in Northern region of England while evidence was gathering on progressive cardiomyopathy in these patients. We wanted to find out the prevalence, progression and clinical features of cardiac involvement in Duchenne and Becker muscular dystrophy. Methods: It is a retrospective review of clinical, electrocardiographic and echocardiographic assessments. The notes of 52 Duchenne and Becker muscular dystrophy patients were reviewed out of which 32 had DMD, 6 had Intermediate muscular dystrophy (IMD) and 14 had BMD. Prevalence of preclinical and clinically evident cardiac involvement was 88.4% in DMD and BMD patients. Sixty nine% of patients had clinically evident cardiac involvement but only four patients had cardiac symptoms in the form of palpitations, out of which two were due to respiratory dysfunction and others was due to cardiac failure. Clinical examination of the rest of all of the patients was unremarkable. Electrocardiogram was abnormal in 88.4% of patients. Conduction defects were found in 19.4% of patients. Echocardiogram was abnormal in 80.7% of patients but all were poor echo subjects including those who had normal echocardiogram. Though most patients were asymptomatic, a high percentage had evidence of preclinical and clinically evident cardiac involvement. So in all patients with Xp21 linked muscular dystrophy a routine baseline cardiac assessment should be done at the age of 10 years and reviewed after intervals of one to two years. (author)

Muscular Dystrophy: Hope Through Research

Science.gov (United States)

... of muscular dystrophy appeared in 1830, when Sir Charles Bell wrote an essay about an illness that ... linked disorder to their sons but their daughters will be carriers of that disorder. Carrier females occasionally ...

How Physicians Support Mothers of Children with Duchenne Muscular Dystrophy.

Science.gov (United States)

Fujino, Haruo; Saito, Toshio; Matsumura, Tsuyoshi; Shibata, Saki; Iwata, Yuko; Fujimura, Harutoshi; Shinno, Susumu; Imura, Osamu

2015-09-01

Communicating about Duchenne muscular dystrophy and its prognosis can be difficult for affected children and their family. We focused on how physicians provide support to the mothers of children with Duchenne muscular dystrophy who have difficulty communicating about the condition with their child. The eligible participants were certified child neurologists of the Japanese Society of Child Neurology. Participants responded to questionnaires consisting of free descriptions of a vignette of a child with Duchenne muscular dystrophy and a mother. We analyzed 263 responses of the participants. We found 4 themes on advising mothers, involving encouraging communication, family autonomy, supporting family, and considering the child's concerns. These results provide a better understanding of the communication between physicians and family members who need help sharing information with a child with Duchenne muscular dystrophy. These findings will assist clinical practitioners in supporting families and the affected children throughout the course of their illness. © The Author(s) 2015.

Muscle-Eye-Brain Disease; a Rare Form of Syndromic Congenital Muscular Dystrophy

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Gosal Gurinder S

2011-03-01

Full Text Available Congenital muscular dystrophy (CMD is a heterogeneous group of disorders characterized by muscular hypotonia since birth and the histologic features of muscular dystrophy. Syndromic congenital muscular dystrophies are clinically similar autosomal recessive disorders characterized by congenital muscular dystrophy, lissencephaly, and eye anomalies. We present a case of a rare form of syndromic congenital muscular dystrophy in an eight year old girl, born of first- degree consanguinity. She had: global developmental delay; a seizure disorder; hypotonia; progressive muscle contractures including bilateral symmetrical flexion contractures of hips, knees, equinus contracture and thoracolumbar scoliosis; diminished deep tendon reflexes: bilateral premature cataract; pseudophakia; and nystagmus. The patient was also highly myopic. Based on clinical features, muscle biopsy and MRI of the brain, a diagnosis of muscle- eye- brain disease was made. Identification of these patients may help to prevent this crippling disorder in the future siblings of probands by utilizing genetic counselling and mutation analysis.

Bilateral nanophthalmos and pigmentary retinal dystrophy--an unusual syndrome.

Science.gov (United States)

Proença, Helena; Castanheira-Dinis, A; Monteiro-Grillo, M

2006-09-01

To report the clinical picture of the rare association of nanophthalmos and pigmentary retinal dystrophy and its cataract surgery outcome. We report a case of a 60-year-old female who presented with bilateral slowly progressive visual loss. The patient presented with bilateral light perception visual acuity, exotropia, brunescent cataract hindering fundus examination and hypodontia. Ultrasonography revealed bilateral nanophthalmos. A visual-evoked potential was also performed preoperatively. Cataract surgery with +40D IOL implantation was uneventful. Postoperative fundus examination revealed pigmentary retinal dystrophy, confirmed by electrophysiologic tests. Glycosaminoglycan urinary excretion was normal. Congenital bilateral nanophthalmos may rarely be associated with pigmentary retinal dystrophy. We suggest thorough preoperative evaluation in nanophthalmic eyes for the exclusion of significant features concerning visual prognosis.

Meaning of Muscular Dystrophy

Science.gov (United States)

... is very similar to Duchenne, except kids with Becker MD may not have problems until much later, when they're teenagers or adults. It takes a long time for their muscles to become weak. How Does a Kid Get Muscular Dystrophy? MD is not contagious (say: con-TAY-juss), ...

Urological manifestations of Duchenne muscular dystrophy.

Science.gov (United States)

Askeland, Eric J; Arlen, Angela M; Erickson, Bradley A; Mathews, Katherine D; Cooper, Christopher S

2013-10-01

Duchenne muscular dystrophy is a dystrophinopathy affecting males that is associated with multiple organ system complications. To our knowledge urological complications of Duchenne muscular dystrophy have been described only anecdotally to date. We reviewed the medical charts of 135 patients with Duchenne or Duchenne-Becker muscular dystrophy for demographics and disease progression, urological diagnoses, intervention and followup. Of 135 patients 67 (50%) had at least 1 documented urological diagnosis and 38 (28%) had multiple manifestations. Lower urinary tract symptoms were the most common urological diagnosis (32% of patients). Survival analysis revealed a median age at onset of lower urinary tract symptoms of 23 years (95% CI 17.7-23.9). Intervention was required in 12 patients (9%), most commonly due to nephrolithiasis. Urological morbidity increased with Duchenne muscular dystrophy progression when stratified by clinical progression. Lower urinary tract symptoms were more common in nonambulatory patients (40.7% vs 19%, p = 0.007), those with a diagnosis of scoliosis (44% vs 19.7%, p = 0.003) and/or scoliosis spine surgery (60% vs 22%, p <0.001), and those on invasive respiratory support (53% vs 29%, p = 0.046). Likewise, nephrolithiasis was more common in nonambulatory patients (10% vs 0%, p = 0.017), those with scoliosis (12% vs 0%, p = 0.004) and/or scoliosis spine surgery (20% vs 1%, p <0.001), and those on invasive respiratory support (29% vs 3%, p <0.001). Only 28% of patients with a urological manifestation were referred to urology. As these patients transition into adolescence and adulthood, the increased prevalence of urological manifestations warrants increased awareness and referral to urologists. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Disparities in the diagnostic process of Duchenne and Becker muscular dystrophy.

Science.gov (United States)

Holtzer, Caleb; Meaney, F John; Andrews, Jennifer; Ciafaloni, Emma; Fox, Deborah J; James, Katherine A; Lu, Zhenqiang; Miller, Lisa; Pandya, Shree; Ouyang, Lijing; Cunniff, Christopher

2011-11-01

To determine whether sociodemographic factors are associated with delays at specific steps in the diagnostic process of Duchenne and Becker muscular dystrophy. We examined abstracted medical records for 540 males from population-based surveillance sites in Arizona, Colorado, Georgia, Iowa, and western New York. We used linear regressions to model the association of three sociodemographic characteristics with age at initial medical evaluation, first creatine kinase measurement, and earliest DNA analysis while controlling for changes in the diagnostic process over time. The analytical dataset included 375 males with information on family history of Duchenne and Becker muscular dystrophy, neighborhood poverty levels, and race/ethnicity. Black and Hispanic race/ethnicity predicted older ages at initial evaluation, creatine kinase measurement, and DNA testing (P Becker muscular dystrophy predicted younger ages at initial evaluation, creatine kinase measurement and DNA testing (P Becker muscular dystrophy are evident even after adjustment for family history of Duchenne and Becker muscular dystrophy and changes in the diagnostic process over time. Black and Hispanic children are initially evaluated at older ages than white children, and the gap widens at later steps in the diagnostic process.

Genetics and emerging treatments for Duchenne and Becker muscular dystrophy.

Science.gov (United States)

Wein, Nicolas; Alfano, Lindsay; Flanigan, Kevin M

2015-06-01

Mutations in the DMD gene result in Duchenne or Becker muscular dystrophy due to absent or altered expression of the dystrophin protein. The more severe Duchenne muscular dystrophy typically presents around ages 2 to 5 with gait disturbance, and historically has led to the loss of ambulation by age 12. It is important for the practicing pediatrician, however, to be aware of other presenting signs, such as delayed motor or cognitive milestones, or elevated serum transaminases. Becker muscular dystrophy is milder, often presenting after age 5, with ambulation frequently preserved past 20 years and sometimes into late decades. Copyright © 2015 Elsevier Inc. All rights reserved.

Limb girdle muscular dystrophy due to mutations in POMT2

DEFF Research Database (Denmark)

Østergaard, Sofie Thurø; Johnson, Katherine; Stojkovic, Tanya

2018-01-01

BACKGROUND: Mutations in the gene coding for protein O-mannosyl-transferase 2 (POMT2) are known to cause severe congenital muscular dystrophy, and recently, mutations in POMT2 have also been linked to a milder limb-girdle muscular dystrophy (LGMD) phenotype, named LGMD type 2N (LGMD2N). Only four...

Adult patient with Becker dystrophy undergoing orthopedic surgery: an anesthesia challenge

Directory of Open Access Journals (Sweden)

Parish M

2018-02-01

Full Text Available Masoud Parish, Haleh Farzin Anesthesiology Department, Tabriz University of Medical Sciences, Shohada Teaching Hospital, Tabriz, Iran Abstract: Muscular dystrophies are considered to be a series of neuromuscular diseases with genetic causes and are characterized by progressive muscle weakness and degeneration of the skeletal muscle. The case of an adult man with Becker dystrophy referred for repair of the patella tendon tearing and patella fracture is described. He underwent successful surgery using total intravenous anesthesia without any complications. Keywords: Becker dystrophy, orthopedic surgery, adult, intravenous anesthesia

[Human myopathy and animal muscular dystrophy].

Science.gov (United States)

Schapira, G; Dreyfus, J C; Schapira, F

1977-08-01

Two hereditary muscular dystrophies similar to human progressive muscular dystrophy (P.M.D. Duchenne type) have been isolated in animals, one in mouse, the other in chicken. The decrease in the activity of glycogenolytic enzymes is similar to that observed in denervated muscle. Isozymic fetal types for several muscular enzymes have been observed as well in chicken as in man, but this fetal type may also be found in neurogenic atrophy. The release in circulation of muscle enzymes seems more specific. But the origin of the genetic lesion is still unknown. We describe here the three different theories about this problem: i.e. neurogenic, vascular, or myogenic. This last theory implies a trouble of membrane permeability.

Lamin A/C mutations with lipodystrophy, cardiac abnormalities, and muscular dystrophy

NARCIS (Netherlands)

van der Kooi, A. J.; Bonne, G.; Eymard, B.; Duboc, D.; Talim, B.; van der Valk, M.; Reiss, P.; Richard, P.; Demay, L.; Merlini, L.; Schwartz, K.; Busch, H. F. M.; de Visser, M.

2002-01-01

Mutations in the lamin A/C gene are found in Emery-Dreifuss muscular dystrophy, limb girdle muscular dystrophy with cardiac conduction disturbances, dilated cardiomyopathy with conduction system disease, and familial partial lipodystrophy. Cases with lamin A/C mutations presenting with lipodystrophy

Common recessive limb girdle muscular dystrophies differential diagnosis: why and how?

Directory of Open Access Journals (Sweden)

Ana Cotta

2014-09-01

Full Text Available Limb girdle muscular dystrophies are heterogeneous autosomal hereditary neuromuscular disorders. They produce dystrophic changes on muscle biopsy and they are associated with mutations in several genes involved in muscular structure and function. Detailed clinical, laboratorial, imaging, diagnostic flowchart, photographs, tables, and illustrated diagrams are presented for the differential diagnosis of common autosomal recessive limb girdle muscular dystrophy subtypes diagnosed nowadays at one reference center in Brazil. Preoperative image studies guide muscle biopsy site selection. Muscle involvement image pattern differs depending on the limb girdle muscular dystrophy subtype. Muscle involvement is conspicuous at the posterior thigh in calpainopathy and fukutin-related proteinopathy; anterior thigh in sarcoglycanopathy; whole thigh in dysferlinopathy, and telethoninopathy. The precise differential diagnosis of limb girdle muscular dystrophies is important for genetic counseling, prognostic orientation, cardiac and respiratory management. Besides that, it may probably, in the future, provide specific genetic therapies for each subtype.

Repair of an inguinoscrotal hernia in a patient with Becker muscular dystrophy.

Science.gov (United States)

Tatulli, F; Caraglia, A; Delcuratolo, A; Cassano, S; Chetta, G S

2017-01-01

Inguinal hernia repairs are routinely performed as outpatient procedures in most patients, whereas a few require admission due to clinical or social peculiarities. Muscular dystrophies are inherited disorders characterized by progressive muscle wasting and weakness. In case of surgery there is no definite recommendation for either general or regional anesthesia. This contribution regards a 48 y. o. male patient diagnosed with Becker Muscular Dystrophy by muscle biopsy 10 years earlier. He had a left-sided sizable inguinoscrotal hernia with repeat episodes of incarceration. An elective mesh repair with suction drainage was accomplished under selective spinal anesthesia. The post-operative course was uneventful. A few inguinal hernia repairs require admission due to peculiarities such as extensive scrotal hernias requiring suction drainage. Muscular dystrophies are inherited disorders with no cure and no two dystrophy patients are exactly alike, therefore the health issues will be different for each individual. In case of surgery there is no definite recommendation for either general or regional anesthesia. This contribution regards the successful elective mesh repair with suction drainage of a large left-sided inguino-scrotal hernia in a 48 y. o. male patient affected by Becker muscular dystrophy by selective spinal anesthesia obtained by 10 milligrams of hyperbaric bupivacaine. Effective mesh repair with suction drainage of large inguinal hernias under spinal anesthesia can be achieved in patients affected by muscular dystrophy.

Serum creatinine level: a supplemental index to distinguish Duchenne muscular dystrophy from Becker muscular dystrophy.

Science.gov (United States)

Zhang, Huili; Zhu, Yuling; Sun, Yiming; Liang, Yingyin; Li, Yaqin; Zhang, Yu; Deng, Langhui; Wen, Xingxuan; Zhang, Cheng

2015-01-01

To improve assessment of dystrophinopathy, the aim of this study was to identify whether serum creatinine (Crn) level reflects disease severity. Biochemical, Vignos score, and genetic data were collected on 212 boys with dystrophinopathy. Serum Crn level had a strong inverse correlation with Vignos score by simple correlation (r = -0.793) and partial correlation analysis after adjustment for age, height, and weight (r = -0.791; both P Becker muscular dystrophy (BMD) patients than Duchenne muscular dystrophy (DMD) patients at ages 4, 5, 7, and 9 yr (all P < 0.0125). After adjusting for age, height, and weight, BMD patients still had a significantly higher serum Crn level than DMD patients (β = 7.140,  t = 6.277,  P < 0.01). Serum Crn level reflected disease severity and may serve as a supplemental index to distinguish DMD from BMD in clinical practice.

[Central aleolar choroidal dystrophy in sibilings coexisting with alopecia].

Science.gov (United States)

Brydak-Godowska, Joanna; Dróbecka-Brydak, Ewa; Paćkowska, Maria; Kecik, Dariusz

2007-01-01

Central areolar choroidal dystrophy is localized in macular region and is characterized by atrophy of pigment epithelium, photoreceptors and choriocapillaris. This paper presents the history of two sibilings at the age of 23 and 30, with central aleolar choroidal dystrophy coexisting with alopecia. The results of erg, eog and fluorescein angiography are presented. The results of therapy for glaucoma associated with the Sturge-Weber syndrome are often disappointing.

Pulmonary Endpoints in Duchenne Muscular Dystrophy. A Workshop Summary.

Science.gov (United States)

Finder, Jonathan; Mayer, Oscar Henry; Sheehan, Daniel; Sawnani, Hemant; Abresch, R Ted; Benditt, Joshua; Birnkrant, David J; Duong, Tina; Henricson, Erik; Kinnett, Kathi; McDonald, Craig M; Connolly, Anne M

2017-08-15

Development of novel therapeutics for treatment of Duchenne muscular dystrophy (DMD) has led to clinical trials that include pulmonary endpoints that allow assessment of respiratory muscle status, especially in nonambulatory subjects. Parent Project Muscular Dystrophy (PPMD) convened a workshop in Bethesda, Maryland, on April 14 and 15, 2016, to summarize published respiratory data in DMD and give guidance to clinical researchers assessing the effect of interventions on pulmonary outcomes in DMD.

Trends with corticosteroid use in males with Duchenne muscular dystrophy born 1982-2001.

Science.gov (United States)

Fox, Deborah J; Kumar, Anil; West, Nancy A; DiRienzo, A Gregory; James, Katherine A; Oleszek, Joyce

2015-01-01

This study examines trends in corticosteroid use for males with Duchenne muscular dystrophy by birth year, race/ethnicity, and knowledge of Duchenne muscular dystrophy family history. Firstborn males (n = 521) selected from a population-based surveillance system of Duchenne muscular dystrophy were analyzed using Kaplan Meier and regression methods. Comparing males born 1982 to 1986 with males born 1997 to 2001, steroid use increased from 54% to 72% and mean age at steroid initiation decreased from 8.2 to 7.1 years. Hispanics and non-Hispanic Black males used steroids less frequently and delayed initiation compared to white males. Compared to males without a Duchenne muscular dystrophy family history, males with known family history were half as likely to use steroids. Duration of steroid use increased over time and age at initiation decreased. Racial/ethnic disparities exist for steroid use and should be addressed to improve outcome and quality of life for boys with Duchenne muscular dystrophy. © The Author(s) 2014.

[Atypical reaction to anesthesia in Duchenne/Becker muscular dystrophy].

Science.gov (United States)

Silva, Helga Cristina Almeida da; Hiray, Marcia; Vainzof, Mariz; Schmidt, Beny; Oliveira, Acary Souza Bulle; Amaral, José Luiz Gomes do

2017-05-31

Duchenne/Becker muscular dystrophy affects skeletal muscles and leads to progressive muscle weakness and risk of atypical anesthetic reactions following exposure to succinylcholine or halogenated agents. The aim of this report is to describe the investigation and diagnosis of a patient with Becker muscular dystrophy and review the care required in anesthesia. Male patient, 14 years old, referred for hyperCKemia (chronic increase of serum creatine kinase levels - CK), with CK values of 7,779-29,040IU.L -1 (normal 174IU.L -1 ). He presented with a discrete delay in motor milestones acquisition (sitting at 9 months, walking at 18 months). He had a history of liver transplantation. In the neurological examination, the patient showed difficulty in walking on one's heels, myopathic sign (hands supported on the thighs to stand), high arched palate, calf hypertrophy, winged scapulae, global muscle hypotonia and arreflexia. Spirometry showed mild restrictive respiratory insufficiency (forced vital capacity: 77% of predicted). The in vitro muscle contracture test in response to halothane and caffeine was normal. Muscular dystrophy analysis by Western blot showed reduced dystrophin (20% of normal) for both antibodies (C and N-terminal), allowing the diagnosis of Becker muscular dystrophy. On preanesthetic assessment, the history of delayed motor development, as well as clinical and/or laboratory signs of myopathy, should encourage neurological evaluation, aiming at diagnosing subclinical myopathies and planning the necessary care to prevent anesthetic complications. Duchenne/Becker muscular dystrophy, although it does not increase susceptibility to MH, may lead to atypical fatal reactions in anesthesia. Copyright © 2017 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

Bortezomib partially improves laminin α2 chain-deficient muscular dystrophy.

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Körner, Zandra; Fontes-Oliveira, Cibely C; Holmberg, Johan; Carmignac, Virginie; Durbeej, Madeleine

2014-05-01

Congenital muscular dystrophy, caused by mutations in LAMA2 (the gene encoding laminin α2 chain), is a severe and incapacitating disease for which no therapy is yet available. We have recently demonstrated that proteasome activity is increased in laminin α2 chain-deficient muscle and that treatment with the nonpharmaceutical proteasome inhibitor MG-132 reduces muscle pathology in laminin α2 chain-deficient dy(3K)/dy(3K) mice. Here, we explore the use of the selective and therapeutic proteasome inhibitor bortezomib (currently used for treatment of relapsed multiple myeloma and mantle cell lymphoma) in dy(3K)/dy(3K) mice and in congenital muscular dystrophy type 1A muscle cells. Outcome measures included quantitative muscle morphology, gene and miRNA expression analyses, proteasome activity, motor activity, and survival. Bortezomib improved several histological hallmarks of disease, partially normalized miRNA expression (miR-1 and miR-133a), and enhanced body weight, locomotion, and survival of dy(3K)/dy(3K) mice. In addition, bortezomib reduced proteasome activity in congenital muscular dystrophy type 1A myoblasts and myotubes. These findings provide evidence that the proteasome inhibitor bortezomib partially reduces laminin α2 chain-deficient muscular dystrophy. Investigation of the clinical efficacy of bortezomib administration in congenital muscular dystrophy type 1A clinical trials may be warranted. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Prednisone Therapy for Duchenne Dystrophy

Directory of Open Access Journals (Sweden)

J Gordon Millichap

2005-02-01

Full Text Available The effects of prednisone on muscle function and the extent of steroid-related adverse effects were studied in 17 ambulant children with Duchenne muscular dystrophy (DMD at University Hospital, Groningen; Rehabilitation Centre, Utrecht; and Leiden University Medical Centre, the Netherlands.

Inherited myopathies and muscular dystrophies

NARCIS (Netherlands)

Cardamone, Michael; Darras, Basil T.; Ryan, Monique M.

The inherited myopathies and muscular dystrophies are a diverse group of muscle diseases presenting with common complaints and physical signs: weakness, motor delay, and respiratory and bulbar dysfunction. The myopathies are caused by genetic defects in the contractile apparatus of muscle, and

Miyoshi-type distal muscular dystrophy. Clinical spectrum in 24 Dutch patients

NARCIS (Netherlands)

Linssen, W. H.; Notermans, N. C.; van der Graaf, Y.; Wokke, J. H.; van Doorn, P. A.; Höweler, C. J.; Busch, H. F.; de Jager, A. E.; de Visser, M.

1997-01-01

Miyoshi-type distal muscular dystrophy has now been found to be more frequent outside Japan than was previously thought. We studied 24 Dutch patients with Miyoshi-type distal muscular dystrophy and focused on its clinical expression and natural history, muscle CT-scans and muscle biopsy findings.

Miyoshi-type distal muscular dystrophy. Clinical spectrum in 24 Dutch patients

NARCIS (Netherlands)

W.H.J.P. Linssen (Wim); N.C. Notermans (Nicolette); Y. van der Graaf (Yolanda); J.H.J. Wokke (John); P.A. van Doorn (Pieter); C.J. Höweler (Chris); H.F.M. Busch (Herman); A.E.J. de Jager (Aeiko); M. de Visser (Marianne)

1997-01-01

textabstractMiyoshi-type distal muscular dystrophy has now been found to be more frequent outside Japan than was previously thought. We studied 24 Dutch patients with Miyoshi-type distal muscular dystrophy and focused on its clinical expression and natural history muscle CT-scans and muscle biopsy

Miyoshi-type distal muscular dystrophy - Clinical spectrum in 24 Dutch patients

NARCIS (Netherlands)

Linssen, WHJP; Notermans, NC; VanderGraaf, Y; Wokke, JHJ; VanDoorn, PA; Howeler, CJ; Busch, HFM; DeJager, AEJ; DeVisser, M

1997-01-01

Miyoshi-type distal muscular dystrophy has now been found to be more frequent outside Japan than was previously thought. We studied 24 Dutch patients with Miyoshi-type distal muscular dystrophy and focused on its clinical expression and natural history, muscle CT-scans and muscle biopsy findings.

Between-day reliability of MyotonPRO for the non-invasive measurement of muscle material properties in the lower extremities of patients with a chronic spinal cord injury.

Science.gov (United States)

Ko, Chang-Yong; Choi, Hyuk-Jae; Ryu, Jeicheong; Kim, Gyoosuk

2018-05-17

Measuring the muscle properties of patients with spinal cord injuries (SCIs) is important to better understand their biomechanical features. In this study, we sought to evaluate the between-day reliability of MyotonPRO, a handheld device that can measure muscle mechanical properties, and assess whether it is reliable to measure muscle properties over time in patients with SCI. Thirteen men with complete SCIs (age 53.9 ± 6.3 years, height 171.0 ± 5.2 cm, weight 66.1 ± 5.8 kg), and injury levels ranging from L1 to T12, were enrolled. Oscillation frequency; logarithmic decrement; dynamic stiffness; mechanical stress relaxation time; and creep of the biceps femoris, medial and lateral gastrocnemius, rectus femoris, tibialis anterior, and Achilles tendon were measured on consecutive days using MyotonPRO. The intraclass coefficient for most muscles and the Achilles tendon ranged from 0.53 to 0.99 for all parameters. The percentage standard error of the measurement for many parameters in most muscles and the Achilles tendon was less than 10%. Bland-Altman analysis showed a high agreement for all mechanical properties. No significant differences were observed in any muscle or Achilles tendon properties between days (all p > 0.05). These results indicate that the MyotonPRO is reliable for between-day measurements of the mechanical properties of lower limb muscles and Achilles tendon in patients with SCI. Copyright © 2018 Elsevier Ltd. All rights reserved.

Autonomic Dysfunction in Muscular Dystrophy: A Theoretical Framework for Muscle Reflex Involvement

Directory of Open Access Journals (Sweden)

Scott Alan Smith

2014-02-01

Full Text Available Muscular dystrophies are a heterogeneous group of genetically inherited disorders whose most prominent clinical feature is progressive degeneration of skeletal muscle. In several forms of the disease, the function of cardiac muscle is likewise affected. The primary defect in this group of diseases is caused by mutations in myocyte proteins important to cellular structure and/or performance. That being stated, a growing body of evidence suggests that the development of autonomic dysfunction may secondarily contribute to the generation of skeletal and cardio-myopathy in muscular dystrophy. Indeed, abnormalities in the regulation of both sympathetic and parasympathetic nerve activity have been reported in a number of muscular dystrophy variants. However, the mechanisms mediating this autonomic dysfunction remain relatively unknown. An autonomic reflex originating in skeletal muscle, the exercise pressor reflex, is known to contribute significantly to the control of sympathetic and parasympathetic activity when stimulated. Given the skeletal myopathy that develops with muscular dystrophy, it is logical to suggest that the function of this reflex might also be abnormal with the pathogenesis of disease. As such, it may contribute to or exacerbate the autonomic dysfunction that manifests. This possibility along with a basic description of exercise pressor reflex function in health and disease are reviewed. A better understanding of the mechanisms that possibly underlie autonomic dysfunction in muscular dystrophy may not only facilitate further research but could also lead to the identification of new therapeutic targets for the treatment of muscular dystrophy.

Dysphagia in facioscapulohumeral muscular dystrophy.

NARCIS (Netherlands)

Wohlgemuth, M.; Swart, B.J.M. de; Kalf, J.G.; Joosten, F.B.M.; Vliet, A.M. van der; Padberg, G.W.A.M.

2006-01-01

Dysphagia is not considered a symptom of facioscapulohumeral muscular dystrophy (FSHD). In this study, the authors found that dysphagia does occur in patients with advanced FSHD showing mild involvement of the jaw and lingual muscles. Dysphagia is seldom life threatening in these patients. The

AMPUTATION AND REFLEX SYMPATHETIC DYSTROPHY

NARCIS (Netherlands)

GEERTZEN, JHB; EISMA, WH

Reflex sympathetic dystrophy is a chronic pain syndrome characterized by chronic burning pain, restricted range of motion, oedema and vasolability. Patients are difficult to treat and the prognosis is very often poor. This report emphasizes that an amputation in case of a reflex sympathetic

Myocardial involvement in muscular dystrophy evaluated by thallium-201 emission computed tomography

International Nuclear Information System (INIS)

Yamamoto, Shuhei; Matsushima, Hideo; Kawai, Naoki; Sotobata, Iwao

1986-01-01

The clinical usefulness of thallium-201 myocardial emission computed tomography (ECT) for evaluating left ventricular myocardial fibrosis was assessed in 47 patients with Duchenne (MD), facio-scapulo-humeral (FSH), limb-girdle (LG) and myotonic (MT) dystrophy. 1. Trans-, long- and short-axial images were interpreted quantitatively by circumferential profile analysis, and the extent of fibrotic tissue (%FIB) was estimated by integrating hypoperfused areas in six to eight consecutive short-axial slices. Lung/mediastinum count ratio (L/M ratio), LV cavity dilatation, aneurysm formation and cardiac malrotation were also assessed with ECT. 2. Distinct ECT defects were demonstrated in 95 of a total of 235 LV segments (40 %) and in 37 of 47 cases (85 % of DMD, 71 % of FSH, 50 % of MT and 60 % of LG). They were observed specifically in the posterior wall (82 %) and the apex (65 %) in DMD, and were scattered in all LV wall segments in FSH, LG, and MT. 3. There was a significant correlation between %FIB and the L/M ratio (r = 0.79, p < 0.001), and the L/M ratio was significantly higher in DMD than in MT (0.67 ± 0.36 vs 0.34 ± 0.25, p < 0.05). 4. ECT showed marked LV dilatation in seven (15 %), apical aneurysm in five (11 %) and vertical heart in 12 (26 %) of the 47 patients. 5. There were no significant correlations between age or clinical stage scores and numbers of defect segments or %FIB in each group. 6. During the one-year follow-up period of these patients, a DMD boy with the largest %FIB (54 %) and the highest L/M ratio (1.4) together with LV dilatation had complications of refractory heart failure and he died eight months following the ECT examination. 7. Thallium-201 planar imaging and standard 12-lead ECG underestimated the perfusion defects which were evaluated with ECT. (author)

Effect of sildenafil on skeletal and cardiac muscle in Becker muscular dystrophy

DEFF Research Database (Denmark)

Witting, Nanna; Kruuse, Christina; Nyhuus, Bo

2014-01-01

OBJECTIVE: Patients with Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy lack neuronal nitric oxide synthase (nNOS). nNOS mediates physiological sympatholysis, thus ensuring adequate blood supply to working muscle. In mice lacking dystrophin, restoration of nNOS effects...

Non-dystrophic myotonia: prospective study of objective and patient reported outcomes.

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Trivedi, Jaya R; Bundy, Brian; Statland, Jeffrey; Salajegheh, Mohammad; Rayan, Dipa Raja; Venance, Shannon L; Wang, Yunxia; Fialho, Doreen; Matthews, Emma; Cleland, James; Gorham, Nina; Herbelin, Laura; Cannon, Stephen; Amato, Anthony; Griggs, Robert C; Hanna, Michael G; Barohn, Richard J

2013-07-01

Non-dystrophic myotonias are rare diseases caused by mutations in skeletal muscle chloride and sodium ion channels with considerable phenotypic overlap between diseases. Few prospective studies have evaluated the sensitivity of symptoms and signs of myotonia in a large cohort of patients. We performed a prospective observational study of 95 participants with definite or clinically suspected non-dystrophic myotonia recruited from six sites in the USA, UK and Canada between March 2006 and March 2009. We used the common infrastructure and data elements provided by the NIH-funded Rare Disease Clinical Research Network. Outcomes included a standardized symptom interview and physical exam; the Short Form-36 and the Individualized Neuromuscular Quality of Life instruments; electrophysiological short and prolonged exercise tests; manual muscle testing; and a modified get-up-and-go test. Thirty-two participants had chloride channel mutations, 34 had sodium channel mutations, nine had myotonic dystrophy type 2, one had myotonic dystrophy type 1, and 17 had no identified mutation. Phenotype comparisons were restricted to those with sodium channel mutations, chloride channel mutations, and myotonic dystrophy type 2. Muscle stiffness was the most prominent symptom overall, seen in 66.7% to 100% of participants. In comparison with chloride channel mutations, participants with sodium mutations had an earlier age of onset of stiffness (5 years versus 10 years), frequent eye closure myotonia (73.5% versus 25%), more impairment on the Individualized Neuromuscular Quality of Life summary score (20.0 versus 9.44), and paradoxical eye closure myotonia (50% versus 0%). Handgrip myotonia was seen in three-quarters of participants, with warm up of myotonia in 75% chloride channel mutations, but also 35.3% of sodium channel mutations. The short exercise test showed ≥10% decrement in the compound muscle action potential amplitude in 59.3% of chloride channel participants compared with 27

Altered cross-bridge properties in skeletal muscle dystrophies

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Aziz eGuellich

2014-10-01

Full Text Available Force and motion generated by skeletal muscle ultimately depends on the cyclical interaction of actin with myosin. This mechanical process is regulated by intracellular Ca2+ through the thin filament-associated regulatory proteins i.e.; troponins and tropomyosin. Muscular dystrophies are a group of heterogeneous genetic affections characterized by progressive degeneration and weakness of the skeletal muscle as a consequence of loss of muscle tissue which directly reduces the number of potential myosin cross-bridges involved in force production. Mutations in genes responsible for skeletal muscle dystrophies have been shown to modify the function of contractile proteins and cross-bridge interactions. Altered gene expression or RNA splicing or post-translational modifications of contractile proteins such as those related to oxidative stress, may affect cross-bridge function by modifying key proteins of the excitation-contraction coupling. Micro-architectural change in myofilament is another mechanism of altered cross-bridge performance. In this review, we provide an overview about changes in cross-bridge performance in skeletal muscle dystrophies and discuss their ultimate impacts on striated muscle function.

Meeting the Assistive Technology Needs of Students with Duchenne Muscular Dystrophy

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Heller, Kathryn Wolff; Mezei, Peter J.; Avant, Mary Jane Thompson

2009-01-01

Students with Duchenne muscular dystrophy (DMD) have a degenerative disease that requires ongoing changes in assistive technology (AT). The AT team needs to be knowledgeable about the disease and its progression in order to meet these students' changing needs in a timely manner. The unique needs of students with Duchenne muscular dystrophy in…

Rimmed vacuoles in Becker muscular dystrophy have similar features with inclusion myopathies.

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Momma, Kazunari; Noguchi, Satoru; Malicdan, May Christine V; Hayashi, Yukiko K; Minami, Narihiro; Kamakura, Keiko; Nonaka, Ikuya; Nishino, Ichizo

2012-01-01

Rimmed vacuoles in myofibers are thought to be due to the accumulation of autophagic vacuoles, and can be characteristic in certain myopathies with protein inclusions in myofibers. In this study, we performed a detailed clinical, molecular, and pathological characterization of Becker muscular dystrophy patients who have rimmed vacuoles in muscles. Among 65 Becker muscular dystrophy patients, we identified 12 patients who have rimmed vacuoles and 11 patients who have deletions in exons 45-48 in DMD gene. All patients having rimmed vacuoles showed milder clinical features compared to those without rimmed vacuoles. Interestingly, the rimmed vacuoles in Becker muscular dystrophy muscles seem to represent autophagic vacuoles and are also associated with polyubiquitinated protein aggregates. These findings support the notion that rimmed vacuoles can appear in Becker muscular dystrophy, and may be related to the chronic changes in muscle pathology induced by certain mutations in the DMD gene.

Rimmed vacuoles in Becker muscular dystrophy have similar features with inclusion myopathies.

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Kazunari Momma

Full Text Available Rimmed vacuoles in myofibers are thought to be due to the accumulation of autophagic vacuoles, and can be characteristic in certain myopathies with protein inclusions in myofibers. In this study, we performed a detailed clinical, molecular, and pathological characterization of Becker muscular dystrophy patients who have rimmed vacuoles in muscles. Among 65 Becker muscular dystrophy patients, we identified 12 patients who have rimmed vacuoles and 11 patients who have deletions in exons 45-48 in DMD gene. All patients having rimmed vacuoles showed milder clinical features compared to those without rimmed vacuoles. Interestingly, the rimmed vacuoles in Becker muscular dystrophy muscles seem to represent autophagic vacuoles and are also associated with polyubiquitinated protein aggregates. These findings support the notion that rimmed vacuoles can appear in Becker muscular dystrophy, and may be related to the chronic changes in muscle pathology induced by certain mutations in the DMD gene.

Myotonic dystrophy: The burden for patients and their partners

NARCIS (Netherlands)

R. Timman (Reinier); A. Tibben (Arend); A.R. Wintzen (Axel)

2010-01-01

textabstractObjective: Dystrophia myotonica is characterized by progressive muscular weakness, myotonia, mental slowness and lack of initiative, which causes problems in daily life both for patients and for their spouses. Some couples seem to deal with these problems satisfactorily, while for others

Muscle-Derived Proteins as Serum Biomarkers for Monitoring Disease Progression in Three Forms of Muscular Dystrophy

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Burch, Peter M.; Pogoryelova, Oksana; Goldstein, Richard; Bennett, Donald; Guglieri, Michela; Straub, Volker; Bushby, Kate; Lochmüller, Hanns; Morris, Carl

2015-01-01

Abstract Background: Identifying translatable, non-invasive biomarkers of muscular dystrophy that better reflect the disease pathology than those currently available would aid the development of new therapies, the monitoring of disease progression and the response to therapy. Objective: The goal of this study was to evaluate a panel of serum protein biomarkers with the potential to specifically detect skeletal muscle injury. Method: Serum concentrations of skeletal troponin I (sTnI), myosin light chain 3 (Myl3), fatty acid binding protein 3 (FABP3) and muscle-type creatine kinase (CKM) proteins were measured in 74 Duchenne muscular dystrophy (DMD), 38 Becker muscular dystrophy (BMD) and 49 Limb-girdle muscular dystrophy type 2B (LGMD2B) patients and 32 healthy controls. Results: All four proteins were significantly elevated in the serum of these three muscular dystrophy patient populations when compared to healthy controls, but, interestingly, displayed different profiles depending on the type of muscular dystrophy. Additionally, the effects of patient age, ambulatory status, cardiac function and treatment status on the serum concentrations of the proteins were investigated. Statistical analysis revealed correlations between the serum concentrations and certain clinical endpoints including forced vital capacity in DMD patients and the time to walk ten meters in LGMD2B patients. Serum concentrations of these proteins were also elevated in two preclinical models of muscular dystrophy, the mdx mouse and the golden-retriever muscular dystrophy dog. Conclusions: These proteins, therefore, are potential muscular dystrophy biomarkers for monitoring disease progression and therapeutic response in both preclinical and clinical studies. PMID:26870665

Zebrafish models flex their muscles to shed light on muscular dystrophies.

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Berger, Joachim; Currie, Peter D

2012-11-01

Muscular dystrophies are a group of genetic disorders that specifically affect skeletal muscle and are characterized by progressive muscle degeneration and weakening. To develop therapies and treatments for these diseases, a better understanding of the molecular basis of muscular dystrophies is required. Thus, identification of causative genes mutated in specific disorders and the study of relevant animal models are imperative. Zebrafish genetic models of human muscle disorders often closely resemble disease pathogenesis, and the optical clarity of zebrafish embryos and larvae enables visualization of dynamic molecular processes in vivo. As an adjunct tool, morpholino studies provide insight into the molecular function of genes and allow rapid assessment of candidate genes for human muscular dystrophies. This unique set of attributes makes the zebrafish model system particularly valuable for the study of muscle diseases. This review discusses how recent research using zebrafish has shed light on the pathological basis of muscular dystrophies, with particular focus on the muscle cell membrane and the linkage between the myofibre cytoskeleton and the extracellular matrix.

SIRT1: A Novel Target for the Treatment of Muscular Dystrophies

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Atsushi Kuno

2016-01-01

Full Text Available Muscular dystrophies are inherited myogenic disorders accompanied by progressive skeletal muscle weakness and degeneration. Duchenne muscular dystrophy (DMD is the most common and severe form of muscular dystrophy and is caused by mutations in the gene that encodes the cytoskeletal protein dystrophin. The treatment for DMD is limited to glucocorticoids, which are associated with multiple side effects. Thus, the identification of novel therapeutic targets is urgently needed. SIRT1 is an NAD+-dependent histone/protein deacetylase that plays roles in diverse cellular processes, including stress resistance and cell survival. Studies have shown that SIRT1 activation provides beneficial effects in the dystrophin-deficient mdx mouse, a model of DMD. SIRT1 activation leads to the attenuation of oxidative stress and inflammation, a shift from the fast to slow myofiber phenotype, and the suppression of tissue fibrosis. Although further research is needed to clarify the molecular mechanisms underlying the protective role of SIRT1 in mdx mice, we propose SIRT1 as a novel therapeutic target for patients with muscular dystrophies.

Delayed healing of corneal epithelium after phototherapeutic keratectomy for lattice dystrophy.

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Das, Sujata; Langenbucher, Achim; Seitz, Berthold

2005-04-01

To evaluate the time period necessary for complete epithelial healing after phototherapeutic keratectomy (o-PTK) carried out for various superficial corneal opacities. A total of 197 eyes were divided into 9 groups: group 1, Cogan dystrophy including recurrences (n = 15); group 2, Reis Bucklers dystrophy including recurrences (n = 12); group 3, granular dystrophy including recurrences (n = 63); group 4, lattice dystrophy including recurrences (n = 19); group 5, macular dystrophy including recurrences (n = 10); group 6, herpetic scars (n = 5); group 7, corneal scars of nonherpetic origin (including scrofulous, traumatic, central keratoconus, post-pterygium surgery) (n = 31); group 8, Salzmann nodular degeneration (n = 22); and group 9, miscellaneous (such as bullous keratopathy, acute chemical burn, corneal degeneration) (n = 20). After o-PTK, patients were examined daily at the slit lamp using fluorescein and blue light. The time period necessary for complete healing of the epithelial defect was compared among these groups. Delayed healing was considered where the epithelium was not closed after 7 days. One hundred sixty-one eyes (95%) healed within 7 days. Overall, 63%, 80%, and 85% of epithelial defects were closed within 3, 4, and 5 days, respectively. Out of 9 eyes that had delayed healing, 6 eyes (67%) belonged to lattice dystrophy category. Mean time taken for healing in group 4 (8.6 +/- 8.4 days) was significantly longer than those in group 1 (3.0 +/- 1.5 days, P = 0.009), group 2 (3.7 +/- 3.1 days, P = 0.03), group 3 (3.1 +/- 1.5 days, P = 0.001), group 5 (2.7 +/- 0.8 days, P = 0.01), group 7 (3.6 +/- 2.4 days, P = 0.007), group 8 (3.3 +/- 1.3 days, P = 0.009), and group 9 (3.0 +/- 1.9 days, P = 0.011). Eyes with lattice corneal dystrophy suffered from delayed epithelial healing after o-PTK. In addition to adequate counseling, these patients should be followed up closely until complete closure of the epithelium to avoid ulceration, scarring, or even

Creatine kinase response to high-intensity aerobic exercise in adult-onset muscular dystrophy

DEFF Research Database (Denmark)

Andersen, Søren P; Sveen, Marie-Louise; Hansen, Regitze S

2013-01-01

We investigated the effect of high-intensity exercise on plasma creatine kinase (CK) in patients with muscular dystrophies.......We investigated the effect of high-intensity exercise on plasma creatine kinase (CK) in patients with muscular dystrophies....

Case of early pelviolumeral progressive muscular dystrophy associated with marked heart affection

International Nuclear Information System (INIS)

Gor'kova, N.B.; Starykh, L.M.; Karpova, L.E.

1991-01-01

A case of early pelviolumeral progressive muscular dystrophy detected in childhood and associated with marked heart affection is described. Patient underwent multimodality examination, including ECG, ultrasonography, roentgenography. It is shown that patients with progressive muscular dystrophy should receive medical supervision and treatment of both neuropathologist and therapist

Abnormal Base Excision Repair at Trinucleotide Repeats Associated with Diseases: A Tissue-Selective Mechanism

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Agathi-Vasiliki Goula

2013-07-01

Full Text Available More than fifteen genetic diseases, including Huntington’s disease, myotonic dystrophy 1, fragile X syndrome and Friedreich ataxia, are caused by the aberrant expansion of a trinucleotide repeat. The mutation is unstable and further expands in specific cells or tissues with time, which can accelerate disease progression. DNA damage and base excision repair (BER are involved in repeat instability and might contribute to the tissue selectivity of the process. In this review, we will discuss the mechanisms of trinucleotide repeat instability, focusing more specifically on the role of BER.

FHL1 reduces dystrophy in transgenic mice overexpressing FSHD muscular dystrophy region gene 1 (FRG1.

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Sandra J Feeney

Full Text Available Facioscapulohumeral muscular dystrophy (FSHD is an autosomal-dominant disease with no effective treatment. The genetic cause of FSHD is complex and the primary pathogenic insult underlying the muscle disease is unknown. Several disease candidate genes have been proposed including DUX4 and FRG1. Expression analysis studies of FSHD report the deregulation of genes which mediate myoblast differentiation and fusion. Transgenic mice overexpressing FRG1 recapitulate the FSHD muscular dystrophy phenotype. Our current study selectively examines how increased expression of FRG1 may contribute to myoblast differentiation defects. We generated stable C2C12 cell lines overexpressing FRG1, which exhibited a myoblast fusion defect upon differentiation. To determine if myoblast fusion defects contribute to the FRG1 mouse dystrophic phenotype, this strain was crossed with skeletal muscle specific FHL1-transgenic mice. We previously reported that FHL1 promotes myoblast fusion in vitro and FHL1-transgenic mice develop skeletal muscle hypertrophy. In the current study, FRG1 mice overexpressing FHL1 showed an improvement in the dystrophic phenotype, including a reduced spinal kyphosis, increased muscle mass and myofiber size, and decreased muscle fibrosis. FHL1 expression in FRG1 mice, did not alter satellite cell number or activation, but enhanced myoblast fusion. Primary myoblasts isolated from FRG1 mice showed a myoblast fusion defect that was rescued by FHL1 expression. Therefore, increased FRG1 expression may contribute to a muscular dystrophy phenotype resembling FSHD by impairing myoblast fusion, a defect that can be rescued by enhanced myoblast fusion via expression of FHL1.

Factitious lymphoedema as a psychiatric condition mimicking reflex sympathetic dystrophy: a case report

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Nwaejike Nnamdi

2008-06-01

Full Text Available Abstract Introduction Reflex sympathetic dystrophy can result in severe disability with only one in five patients able to fully resume prior activities. Therefore, it is important to diagnose this condition early and begin appropriate treatment. Factitious lymphoedema can mimic reflex sympathetic dystrophy and is caused by self-inflicted tourniquets, blows to the arm or repeated skin irritation. Patients with factitious lymphoedema have an underlying psychiatric disorder but usually present to emergency or orthopaedics departments. Factitious lymphoedema can then be misdiagnosed as reflex sympathetic dystrophy. The treatment for factitious lymphoedema is dealing with the underlying psychiatric condition. Case presentation We share our experience of treating a 33-year-old man, who presented with factitious lymphoedema, initially diagnosed as reflex sympathetic dystrophy. Conclusion Awareness of this very similar differential diagnosis allows early appropriate treatment to be administered.

Hereditary muscular dystrophies and the heart

NARCIS (Netherlands)

Hermans, M. C. E.; Pinto, Y. M.; Merkies, I. S. J.; de Die-Smulders, C. E. M.; Crijns, H. J. G. M.; Faber, C. G.

2010-01-01

Cardiac disease is a common clinical manifestation of neuromuscular disorders, particularly of muscular dystrophies. Heart muscle cells as well as specialized conducting myocardial fibres may be affected by the dystrophic process. The incidence and nature of cardiac involvement vary with different

Adult patient with Becker dystrophy undergoing orthopedic surgery: an anesthesia challenge.

Science.gov (United States)

Parish, Masoud; Farzin, Haleh

2018-01-01

Muscular dystrophies are considered to be a series of neuromuscular diseases with genetic causes and are characterized by progressive muscle weakness and degeneration of the skeletal muscle. The case of an adult man with Becker dystrophy referred for repair of the patella tendon tearing and patella fracture is described. He underwent successful surgery using total intravenous anesthesia without any complications.

A Study of CAP-1002 in Ambulatory and Non-Ambulatory Patients With Duchenne Muscular Dystrophy

Science.gov (United States)

2018-04-17

Muscular Dystrophies; Muscular Dystrophy, Duchenne; Muscular Disorders, Atrophic; Muscular Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn

Duchenne and Becker muscular dystrophy in adolescents: current perspectives

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Andrews JG

2018-03-01

Full Text Available Jennifer G Andrews, Richard A Wahl Department of Pediatrics, University of Arizona, Tucson, AZ, USA Abstract: Duchenne muscular dystrophy (DMD and Becker muscular dystrophy (BMD are life-limiting and progressive neuromuscular conditions with significant comorbidities, many of which manifest during adolescence. BMD is a milder presentation of the condition and much less prevalent than DMD, making it less represented in the literature, or more severely affected individuals with BMD may be subsumed into the DMD population using clinical cutoffs. Numerous consensus documents have been published on the clinical management of DMD, the most recent of which was released in 2010. The advent of these clinical management consensus papers, particularly respiratory care, has significantly increased the life span for these individuals, and the adolescent years are now a point of transition into adult lives, rather than a period of end of life. This review outlines the literature on DMD and BMD during adolescence, focusing on clinical presentation during adolescence, impact of living with a chronic illness on adolescents, and the effect that adolescents have on their chronic illness. In addition, we describe the role that palliative-care specialists could have in improving outcomes for these individuals. The increasing proportion of individuals with DMD and BMD living into adulthood underscores the need for more research into interventions and intracacies of adolescence that can improve the social aspects of their lives. Keywords: adolescent health, review, Duchenne muscular dystrophy, Becker muscular dystrophy, dystrophinopathy, palliative care

Dystrophin Immunity in Duchenne’s Muscular Dystrophy

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Mendell, Jerry R.; Campbell, Katherine; Rodino-Klapac, Louise; Sahenk, Zarife; Shilling, Chris; Lewis, Sarah; Bowles, Dawn; Gray, Steven; Li, Chengwen; Galloway, Gloria; Malik, Vinod; Coley, Brian; Clark, K. Reed; Li, Juan; Xiao, Xiao; Samulski, Jade; McPhee, Scott W.; Samulski, R. Jude; Walker, Christopher M.

2010-01-01

SUMMARY We report on delivery of a functional dystrophin transgene to skeletal muscle in six patients with Duchenne’s muscular dystrophy. Dystrophin-specific T cells were detected after treatment, providing evidence of transgene expression even when the functional protein was not visualized in skeletal muscle. Circulating dystrophin-specific T cells were unexpectedly detected in two patients before vector treatment. Revertant dystrophin fibers, which expressed functional, truncated dystrophin from the deleted endogenous gene after spontaneous in-frame splicing, contained epitopes targeted by the autoreactive T cells. The potential for T-cell immunity to self and nonself dystrophin epitopes should be considered in designing and monitoring experimental therapies for this disease. (Funded by the Muscular Dystrophy Association and others; ClinicalTrials.gov number, NCT00428935.) PMID:20925545

Vibration therapy tolerated in children with Duchenne muscular dystrophy: a pilot study.

Science.gov (United States)

Myers, Kenneth A; Ramage, Barbara; Khan, Aneal; Mah, Jean K

2014-07-01

Duchenne muscular dystrophy is an X-linked recessive muscular dystrophy. Clinical management primarily involves rehabilitation strategies aimed at preserving functional mobility as long as possible. Side-alternating vibration therapy is a rehabilitation intervention that has shown promise in a number of different neuromuscular disorders, and has the potential to preserve strength, functional mobility, and bone mass. There has been little research regarding the tolerance to side-alternating vibration therapy in muscle diseases such as Duchenne muscular dystrophy. Four patients were recruited for a pilot study assessing the safety and tolerance of side-alternating vibration therapy in individuals with Duchenne muscular dystrophy. All patients participated in a 4-week training period involving side-alternating vibration therapy sessions three times per week. Serum creatine kinase was measured, and adverse effects reviewed at each session with functional mobility assessed before and after the training period. All patients tolerated the training protocol well, and there were no major changes in functional mobility. One patient had a transient increase in creatine kinase during the study; however, levels of this enzyme were stable overall when comparing the pretraining and posttraining values. Some patients reported subjective improvement during the training period. Side-alternating vibration therapy is well tolerated in children with Duchenne muscular dystrophy and may have potential to improve or maintain functional mobility and strength in these patients. Copyright © 2014 Elsevier Inc. All rights reserved.

Brain Function in Duchenne Muscular Dystrophy

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J. Gordon Millichap

2002-02-01

Full Text Available The role of dystrophin disorders in the CNS function of boys with Duchenne muscular dystrophy (DMD and the dystrophin-deficient mdx mouse, an animal model of DMD, is reviewed at the University of New South Wales, University of Sydney, Australia.

Clinical Course, Genetic Etiology, and Visual Outcome in Cone and Cone-Rod Dystrophy

NARCIS (Netherlands)

Thiadens, Alberta A. H. J.; Phan, T. My Lan; Zekveld-Vroon, Renate C.; Leroy, Bart P.; van den Born, L. Ingeborgh; Hoyng, Carel B.; Klaver, Caroline C. W.; Roosing, Susanne; Pott, Jan-Willem R.; van Schooneveld, Mary J.; van Moll-Ramirez, Norka; van Genderen, Maria M.; Boon, Camiel J. F.; den Hollander, Anneke I.; Bergen, Arthur A. B.; De Baere, Elfride; Cremers, Frans P. M.; Lotery, Andrew J.

Objective: To evaluate the clinical course, genetic etiology, and visual prognosis in patients with cone dystrophy (CD) and cone-rod dystrophy (CRD). Design: Clinic-based, longitudinal, multicenter study. Participants: Consecutive probands with CD (N = 98), CRD (N = 83), and affected relatives (N =

Management of myocardial damage in muscular dystrophy

International Nuclear Information System (INIS)

Tamura, Takuhisa

2011-01-01

Heart failure (HF) is a fatal complication in many muscular dystrophy cases and has become the most common cause of death in Duchenne muscular dystrophy (DMD) since 2001. HF deaths in DMD occur in young patients and increase, along with respiratory failure, in older patients. Managing HF, therefore, is the most important component of DMD treatment. Management of HF is necessary in DMD patients of all ages because myocardial damage progresses regardless of age and disability. Electrocardiography, echocardiography, myocardial single-photon emission computed tomography (SPECT), and natriuretic peptides are used for the diagnosis of myocardial damage and chronic HF. Tissue Doppler echocardiography is in particularly useful for early detection of minute myocardial damage and dysfunction in DMD. The first-line drugs for chronic HF are angiotensin-converting enzyme inhibitors, and the prognosis of DMD patients has been improved using these drugs and beta-blockers. Diuretics are added in the presence of pulmonary congestion. Digoxin is most effective at a blood level of 0.5-0.8 ng/mL because of its pharmacokinetics in DMD. Surgical treatment may be necessary in cases of intractable HF. Cardiac resynchronization therapy (biventricular pacing), a treatment with an artificial pacemaker, is indicated for cases that meet specific criteria, including HF with ventricular dyssynchrony. Applications of partial left ventriculectomy (Batista procedure) and left ventricular assist devices in muscular dystrophy are likely in the near future. (author)

Congenital muscular dystrophies--problems of classification.

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Lenard, H G

1991-04-01

The classification of congenital muscular dystrophies (CMD), based on perceived clinical and morphological similarities or differences, is controversial. CMD without cerebral involvement has sometimes been divided into a mild and a severe form. This distinction is, however, arbitrary and not uncontested. Whether Ullrich's disease, formerly called atonic-sclerotic dystrophy, is a disease entity and if so, whether it is a primary muscle disorder, is uncertain. CMD without cerebral involvement is inherited in an autosomal recessive fashion in the great majority of cases. CMDs with cerebral involvement are usually classified into at least three forms: the Fukuyama type of CMD, occurring almost exclusively in Japanese patients; CMD with hypomyelination, sometimes also called the occidental type of cerebromuscular dystrophy; and Walker-Warburg syndrome. Muscle-eye-brain disease, described in a number of Finnish patients, may or may not belong in this last category. In CMD with cerebral involvement inheritance is also autosomal recessive. It is possible that single sporadic cases are phenocopies due to infectious or other exogenous causes. Reports of clinical and morphological findings from an increasing number of patients show a high degree of variability within and, on the other hand, certain similarities between the forms of CMD with cerebral involvement. In addition, neuroradiological changes are also found with increasing frequency in CMD patients without clinical neuropsychological abnormalities. It is not unreasonable to speculate that molecular genetic techniques will reveal in the near future a variable defect in one gene locus or defects in a few gene loci as the cause of the various clinical forms of CMDs.

Complementary and alternative medicine for Duchenne and Becker muscular dystrophies: characteristics of users and caregivers.

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Zhu, Yong; Romitti, Paul A; Conway, Kristin M; Andrews, Jennifer; Liu, Ke; Meaney, F John; Street, Natalie; Puzhankara, Soman; Druschel, Charlotte M; Matthews, Dennis J

2014-07-01

Complementary and alternative medicine is frequently used in the management of chronic pediatric diseases, but little is known about its use by those with Duchenne or Becker muscular dystrophy. Complementary and alternative medicine use by male patients with Duchenne or Becker muscular dystrophy and associations with characteristics of male patients and their caregivers were examined through interviews with 362 primary caregivers identified from the Muscular Dystrophy Surveillance, Tracking, and Research Network. Overall, 272 of the 362 (75.1%) primary caregivers reported that they had used any complementary and alternative medicine for the oldest Muscular Dystrophy Surveillance, Tracking, and Research Network male in their family. The most commonly reported therapies were from the mind-body medicine domain (61.0%) followed by those from the biologically based practice (39.2%), manipulative and body-based practice (29.3%), and whole medical system (6.9%) domains. Aquatherapy, prayer and/or blessing, special diet, and massage were the most frequently used therapies. Compared with nonusers, male patients who used any therapy were more likely to have an early onset of symptoms and use a wheel chair; their caregivers were more likely to be non-Hispanic white. Among domains, associations were observed with caregiver education and family income (mind-body medicines [excluding prayer and/or blessing only] and whole medical systems) and Muscular Dystrophy Surveillance, Tracking, and Research Network site (biologically based practices and mind-body medicines [excluding prayer and/or blessing only]). Complementary and alternative medicine use was common in the management of Duchenne and Becker muscular dystrophies among Muscular Dystrophy Surveillance, Tracking, and Research Network males. This widespread use suggests further study to evaluate the efficacy of integrating complementary and alternative medicine into treatment regimens for Duchenne and Becker muscular

Serum Creatinine Level: A Supplemental Index to Distinguish Duchenne Muscular Dystrophy from Becker Muscular Dystrophy

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Huili Zhang

2015-01-01

Full Text Available Background. To improve assessment of dystrophinopathy, the aim of this study was to identify whether serum creatinine (Crn level reflects disease severity. Methods. Biochemical, Vignos score, and genetic data were collected on 212 boys with dystrophinopathy. Results. Serum Crn level had a strong inverse correlation with Vignos score by simple correlation (r=-0.793 and partial correlation analysis after adjustment for age, height, and weight (r=-0.791; both P<0.01. Serum Crn level was significantly higher in patients with in-frame than out-of-frame mutations (Z=-4.716, P<0.01 and in Becker muscular dystrophy (BMD patients than Duchenne muscular dystrophy (DMD patients at ages 4, 5, 7, and 9 yr (all P<0.0125. After adjusting for age, height, and weight, BMD patients still had a significantly higher serum Crn level than DMD patients (β=7.140, t=6.277, P<0.01. Conclusions. Serum Crn level reflected disease severity and may serve as a supplemental index to distinguish DMD from BMD in clinical practice.

Prevalence and Diagnostic Spectrum of Generalized Retinal Dystrophy in Danish Children

DEFF Research Database (Denmark)

Bertelsen, Mette; Jensen, Hanne; Larsen, Michael

2013-01-01

Abstract Purpose: The aim of the present population-based cross-sectional study was to examine the prevalence and diagnostic spectrum of generalized retinal dystrophy in Danish children. Methods: The Danish Registry for the Blind and Partially Sighted Children comprises all visually impaired......: Of the 1,204,235 Danish children aged 0-17 years on 1 October 2011, 2017 children were registered as visually impaired. Of these, 153 cases were attributed to generalized retinal dystrophy, corresponding to a prevalence of 13 per 100,000 children. The age-specific prevalence increased prominently...... children residing in Denmark aged 0-17 years. Among registered children, the primary diagnosis of generalized retinal dystrophy was assessed by chart review, including fundus photographs and electroretinograms. Age-specific data for live children in Denmark were retrieved from Statistics Denmark. Results...

How Do People Cope with Muscular Dystrophy?

Science.gov (United States)

... topic are answered in this section. How do people cope with muscular dystrophy (MD)? Although MD presents ... improve health and quality of life. Almost all people with any form of MD experience a worsening ...

Sarcopenia and sarcopenic obesity in patients with muscular dystrophy

Directory of Open Access Journals (Sweden)

Luciano eMerlini

2014-10-01

Full Text Available Aging sarcopenia and muscular dystrophy are two conditions characterized by lower skeletal muscle quantity, lower muscle strength, and lower physical performance. Aging is associated with a peculiar alteration in body composition called sarcopenic obesity characterized by a decrease in lean body mass and increase in fat mass. To evaluate the presence of sarcopenia and obesity in a cohort of adult patients with muscular dystrophy we have used the measurement techniques considered golden standard for sarcopenia that is for muscle mass dual energy X-ray absorptiometry (DXA, for muscle strength hand held dynamometry, and for physical performance gait speed. The study involved 14 adult patients with different types of muscular dystrophy. We were able to demonstrate that all patient were sarcopenic-obese. We showed in fact that all were sarcopenic based on appendicular lean, fat & bone free, mass index (ALMI. In addition all resulted obese according to the % of body fat determined by DXA in contrast with their body mass index ranging from underweight to obese. Skeletal muscle mass determined by DXA was markedly reduced in all patients and correlated with residual muscle strength determined by hand held dynamometry, and physical performances determined by gait speed and respiratory function. Finally we showed that ALMI was the best linear explicator of muscle strength and physical function. Altogether, our study suggest the relevance of a proper evaluation of body composition in muscular dystrophy and we propose to use, both in research and practice, the measurement techniques that has already been demonstrated effective in aging sarcopenia.

The Intriguing Regulators of Muscle Mass in Sarcopenia and Muscular Dystrophy

OpenAIRE

Sakuma, Kunihiro; Aoi, Wataru; Yamaguchi, Akihiko

2014-01-01

Recent advances in our understanding of the biology of muscle have led to new interest in the pharmacological treatment of muscle wasting. Loss of muscle mass and increased intramuscular fibrosis occur in both sarcopenia and muscular dystrophy. Several regulators (mammalian target of rapamycin, serum response factor, atrogin-1, myostatin, etc.) seem to modulate protein synthesis and degradation or transcription of muscle-specific genes during both sarcopenia and muscular dystrophy. This revie...

Molecular biology of human muscle disease

Energy Technology Data Exchange (ETDEWEB)

Dunne, P.W.; Epstein, H.F. (Baylor Coll. of Medicine, Houston, TX (United States))

1991-01-01

The molecular revolution that is transforming the entire biomedical field has had far-reaching impact in its application to inherited human muscle disease. The gene for Duchenne muscular dystrophy was one of the first cloned without knowledge of the defective protein product. This success was based upon the availability of key chromosomal aberrations that provided molecular landmarks for the disease locus. Subsequent discoveries regarding the mode of expression for this gene, the structure and localization of its protein product dystrophin, and molecular diagnosis of affected and carrier individuals constitute a paradigm for investigation of human genetics. Finding the gene for myotonic muscular dystrophy is requiring the brute force approach of cloning several million bases of DNA, identifying expressed sequences, and characterizing candidate genes. The gene that causes hypertrophic cardiomyopathy has been found serendipitously to be one of the genetic markers on chromosome 14, the {beta} myosin heavy chain.

Oxidative stress and pathology in muscular dystrophies: focus on protein thiol oxidation and dysferlinopathies.

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Terrill, Jessica R; Radley-Crabb, Hannah G; Iwasaki, Tomohito; Lemckert, Frances A; Arthur, Peter G; Grounds, Miranda D

2013-09-01

The muscular dystrophies comprise more than 30 clinical disorders that are characterized by progressive skeletal muscle wasting and degeneration. Although the genetic basis for many of these disorders has been identified, the exact mechanism for pathogenesis generally remains unknown. It is considered that disturbed levels of reactive oxygen species (ROS) contribute to the pathology of many muscular dystrophies. Reactive oxygen species and oxidative stress may cause cellular damage by directly and irreversibly damaging macromolecules such as proteins, membrane lipids and DNA; another major cellular consequence of reactive oxygen species is the reversible modification of protein thiol side chains that may affect many aspects of molecular function. Irreversible oxidative damage of protein and lipids has been widely studied in Duchenne muscular dystrophy, and we have recently identified increased protein thiol oxidation in dystrophic muscles of the mdx mouse model for Duchenne muscular dystrophy. This review evaluates the role of elevated oxidative stress in Duchenne muscular dystrophy and other forms of muscular dystrophies, and presents new data that show significantly increased protein thiol oxidation and high levels of lipofuscin (a measure of cumulative oxidative damage) in dysferlin-deficient muscles of A/J mice at various ages. The significance of this elevated oxidative stress and high levels of reversible thiol oxidation, but minimal myofibre necrosis, is discussed in the context of the disease mechanism for dysferlinopathies, and compared with the situation for dystrophin-deficient mdx mice. © 2013 The Authors Journal compilation © 2013 FEBS.

Secondary Conditions Among Males With Duchenne or Becker Muscular Dystrophy.

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Latimer, Rebecca; Street, Natalie; Conway, Kristin Caspers; James, Kathy; Cunniff, Christopher; Oleszek, Joyce; Fox, Deborah; Ciafaloni, Emma; Westfield, Christina; Paramsothy, Pangaja

2017-06-01

Duchenne and Becker muscular dystrophy are X-linked neuromuscular disorders characterized by progressive muscle degeneration. Despite the involvement of multiple systems, secondary conditions among affected males have not been comprehensively described. Two hundred nine caregivers of affected males (aged 3-31 years) identified by the Muscular Dystrophy Surveillance, Tracking, and Research Network completed a mailed survey that included questions about secondary conditions impacting multiple body functions. The 5 most commonly reported conditions in males with Duchenne were cognitive deficits (38.4%), constipation (31.7%), anxiety (29.3%), depression (27.4%), and obesity (19.5%). Higher frequencies of anxiety, depression, and kidney stones were found among nonambulatory males compared to ambulatory males. Attention-deficit hyperactivity disorder (ADHD) was more common in ambulatory than nonambulatory males. These data support clinical care recommendations for monitoring of patients with Duchenne or Becker muscular dystrophy by a multidisciplinary team to prevent and treat conditions that may be secondary to the diagnosis.

Anti-gravity training improves walking capacity and postural balance in patients with muscular dystrophy

DEFF Research Database (Denmark)

Berthelsen, Martin Peter; Husu, Edith; Christensen, Sofie Bouschinger

2014-01-01

of their weakness. We investigated the functional effects of combined aerobic and strength training in patients with Becker and limb-girdle muscular dystrophies with knee muscle strength levels as low as 3% of normal strength. Eight patients performed 10weeks of aerobic and strength training on an anti...... affected patients with Becker and limb-girdle muscular dystrophies.......Recent studies in patients with muscular dystrophies suggest positive effects of aerobic and strength training. These studies focused training on using bicycle ergometers and conventional strength training, which precludes more severely affected patients from participating, because...

Emerging genetic therapies to treat Duchenne muscular dystrophy

Science.gov (United States)

Nelson, Stanley F.; Crosbie, Rachelle H.; Miceli, M. Carrie; Spencer, Melissa J.

2010-01-01

Purpose of review Duchenne muscular dystrophy is a progressive muscle degenerative disease caused by dystrophin mutations. The purpose of this review is to highlight two emerging therapies designed to repair the primary genetic defect, called `exon skipping' and `nonsense codon suppression'. Recent findings A drug, PTC124, was identified that suppresses nonsense codon translation termination. PTC124 can lead to restoration of some dystrophin expression in human Duchenne muscular dystrophy muscles with mutations resulting in premature stops. Two drugs developed for exon skipping, PRO051 and AVI-4658, result in the exclusion of exon 51 from mature mRNA. They can restore the translational reading frame to dystrophin transcripts from patients with a particular subset of dystrophin gene deletions and lead to some restoration of dystrophin expression in affected boys' muscle in vivo. Both approaches have concluded phase I trials with no serious adverse events. Summary These novel therapies that act to correct the primary genetic defect of dystrophin deficiency are among the first generation of therapies tailored to correct specific mutations in humans. Thus, they represent paradigm forming approaches to personalized medicine with the potential to lead to life changing treatment for those affected by Duchenne muscular dystrophy. PMID:19745732

Glucocorticoids for Duchenne Muscular Dystrophy

Directory of Open Access Journals (Sweden)

J Gordon Millichap

2013-07-01

Full Text Available Investigators at the Dubowitz Neuromuscular Centre, Great Ormond Street Hospital, and other centers in the UK, conducted a prospective longitudinal study across 17 neuromuscular centers in the UK of 360 boys aged 3-15 years with Duchenne muscular dystrophy who were treated with daily or intermittent (10 days on/10 days off prednisolone for a mean duration of 4 years.

Late-onset Becker-type muscular dystrophy in a Border terrier dog.

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Jeandel, A; Garosi, L S; Davies, L; Guo, L T; Salgüero, R; Shelton, G D

2018-01-29

A 9-year-old Border terrier was presented to a referral hospital after a 1-year history of progressive stiffness and exercise intolerance. Neurological examination was consistent with a neuromuscular disorder. Serum creatine kinase activity was mildly elevated. A myopathy was suspected based on MRI findings and electrophysiological examination. Muscle histopathology was consistent with a severe non-inflammatory myopathy of a dystrophic type. Immunofluorescence and western blotting confirmed a dystrophinopathy with an 80-kDa truncated dystrophin fragment similar to Becker muscular dystrophy in people. To our knowledge, this is the first description of a late-onset Becker-type muscular dystrophy in a dog, and the first description of a dystrophinopathy in a Border terrier. Muscular dystrophy in dogs should not be ruled out based on late onset clinical signs and only mildly elevated creatine kinase. © 2018 British Small Animal Veterinary Association.

Sparks, signals and shock absorbers: how dystrophin loss causes muscular dystrophy.

Science.gov (United States)

Batchelor, Clare L; Winder, Steve J

2006-04-01

The dystrophin-glycoprotein complex (DGC) can be considered as a specialized adhesion complex, linking the extracellular matrix to the actin cytoskeleton, primarily in muscle cells. Mutations in several components of the DGC lead to its partial or total loss, resulting in various forms of muscular dystrophy. These typically manifest as progressive wasting diseases with loss of muscle integrity. Debate is ongoing about the precise function of the DGC: initially a strictly mechanical role was proposed but it has been suggested that there is aberrant calcium handling in muscular dystrophy and, more recently, changes in MAP kinase and GTPase signalling have been implicated in the aetiology of the disease. Here, we discuss new and interesting developments in these aspects of DGC function and attempt to rationalize the mechanical, calcium and signalling hypotheses to provide a unifying hypothesis of the underlying process of muscular dystrophy.

The analysis of the clinical and tool parameters characterizing a cardiomyopathyat various forms of the progressing muscular dystrophies

Directory of Open Access Journals (Sweden)

Poverennova I.E.

2017-03-01

Full Text Available Purpose: studying of clinical and tool characteristics of cardiomyopathies at various forms of the progressing muscular dystrophies. Material and methods. There had been 103 patients with hereditary forms of the progressing muscular dystrophies examined, among which 35 persons were with Duchenne muscular dystrophy, 28 with an atrophic myo-tonia, and 40 with a limb girdle dystrophy is conducted. Assessment of clinical and tool features of cardiomyopathies at these types of the hereditary progressing muscular dystrophies had been carried out. Results. In the group of patients with diffusion damage of a myocardium in the form of dystrophic violations had been revealed. Existence of a negative tooth of T in some assignments and lengthenings of an interval of QT is noted. With a dystrophic myotonia violation of a warm rhythm occurred at patients by 87 times more often than in the group of comparison. Violation of a rhythm of heart in group of patients with a limb girdle dystrophy came to light 91 times more often in reference to the group of comparison. Conclusion. Violations in a cardiovascular system at Duchenne muscular dystrophy are preferentially diffusion changes in a myocardium. At a dystrophic myotonia and a limb girdle dystrophy cardial violations concern mainly excitability and the conductivity of heart which are the main reason of developing of this disease at these patients.

Physical Therapy and Facioscapulohumeral Muscular Dystrophy (FSHD)

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Physical Therapy & FSHD Facioscapulohumeral Muscular Dystrophy A Guide for Patients & Physical Therapists Authors: Wendy M. King, P.T., Assistant ... Shree Pandya, P.T., M.S., Assistant Professor, Neurology & Physical Medicine and Rehabilitation A publication of the FSH ...

RNA FISH for detecting expanded repeats in human diseases.

Science.gov (United States)

Urbanek, Martyna O; Krzyzosiak, Wlodzimierz J

2016-04-01

RNA fluorescence in situ hybridization (FISH) is a widely used technique for detecting transcripts in fixed cells and tissues. Many variants of RNA FISH have been proposed to increase signal strength, resolution and target specificity. The current variants of this technique facilitate the detection of the subcellular localization of transcripts at a single molecule level. Among the applications of RNA FISH are studies on nuclear RNA foci in diseases resulting from the expansion of tri-, tetra-, penta- and hexanucleotide repeats present in different single genes. The partial or complete retention of mutant transcripts forming RNA aggregates within the nucleoplasm has been shown in multiple cellular disease models and in the tissues of patients affected with these atypical mutations. Relevant diseases include, among others, myotonic dystrophy type 1 (DM1) with CUG repeats, Huntington's disease (HD) and spinocerebellar ataxia type 3 (SCA3) with CAG repeats, fragile X-associated tremor/ataxia syndrome (FXTAS) with CGG repeats, myotonic dystrophy type 2 (DM2) with CCUG repeats, amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) with GGGGCC repeats and spinocerebellar ataxia type 32 (SCA32) with GGCCUG. In this article, we summarize the results obtained with FISH to examine RNA nuclear inclusions. We provide a detailed protocol for detecting RNAs containing expanded CAG and CUG repeats in different cellular models, including fibroblasts, lymphoblasts, induced pluripotent stem cells and murine and human neuronal progenitors. We also present the results of the first single-molecule FISH application in a cellular model of polyglutamine disease. Copyright © 2015 Elsevier Inc. All rights reserved.

Clinical and molecular characterization of limb-girdle muscular dystrophy due to LAMA2 mutations

DEFF Research Database (Denmark)

Gavassini, Bruno F; Carboni, Nicola; Nielsen, Jørgen E

2011-01-01

In this study we describe the clinical and molecular characteristics of limb-girdle muscular dystrophy (LGMD) due to LAMA2 mutations.......In this study we describe the clinical and molecular characteristics of limb-girdle muscular dystrophy (LGMD) due to LAMA2 mutations....

Duchenne muscular dystrophy - a molecular service

African Journals Online (AJOL)

In 1987 a carrier detection and prenatal diagnostic service for. Duchenne muscular dystrophy using molecular technology was instituted at the Department of Human Genetics, Uni- versity of Cape Town, to serve affe.cted families in southern. Africa. DNA samples from 100 affected male subjects and. 350 of their relatives ...

Muscle regeneration and inflammation in patients with facioscapulohumeral muscular dystrophy

DEFF Research Database (Denmark)

Hauerslev, S; Ørngreen, M C; Hertz, J M

2013-01-01

The aim of this study was to investigate whether inflammation and regeneration are prominent in mildly affected muscles of patients with facioscapulohumeral muscular dystrophy type 1A (FSHD1A). Inflammation in muscle has been suggested by MRI studies in patients with FSHD1A.......The aim of this study was to investigate whether inflammation and regeneration are prominent in mildly affected muscles of patients with facioscapulohumeral muscular dystrophy type 1A (FSHD1A). Inflammation in muscle has been suggested by MRI studies in patients with FSHD1A....

Skeletal Muscle Metabolism in Duchenne and Becker Muscular Dystrophy-Implications for Therapies.

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Heydemann, Ahlke

2018-06-20

The interactions between nutrition and metabolism and skeletal muscle have long been known. Muscle is the major metabolic organ—it consumes more calories than other organs—and therefore, there is a clear need to discuss these interactions and provide some direction for future research areas regarding muscle pathologies. In addition, new experiments and manuscripts continually reveal additional highly intricate, reciprocal interactions between metabolism and muscle. These reciprocal interactions include exercise, age, sex, diet, and pathologies including atrophy, hypoxia, obesity, diabetes, and muscle myopathies. Central to this review are the metabolic changes that occur in the skeletal muscle cells of muscular dystrophy patients and mouse models. Many of these metabolic changes are pathogenic (inappropriate body mass changes, mitochondrial dysfunction, reduced adenosine triphosphate (ATP) levels, and increased Ca 2+ ) and others are compensatory (increased phosphorylated AMP activated protein kinase (pAMPK), increased slow fiber numbers, and increased utrophin). Therefore, reversing or enhancing these changes with therapies will aid the patients. The multiple therapeutic targets to reverse or enhance the metabolic pathways will be discussed. Among the therapeutic targets are increasing pAMPK, utrophin, mitochondrial number and slow fiber characteristics, and inhibiting reactive oxygen species. Because new data reveals many additional intricate levels of interactions, new questions are rapidly arising. How does muscular dystrophy alter metabolism, and are the changes compensatory or pathogenic? How does metabolism affect muscular dystrophy? Of course, the most profound question is whether clinicians can therapeutically target nutrition and metabolism for muscular dystrophy patient benefit? Obtaining the answers to these questions will greatly aid patients with muscular dystrophy.

An unusual variant of Becker muscular dystrophy

NARCIS (Netherlands)

de Visser, M.; Bakker, E.; Defesche, J. C.; Bolhuis, P. A.; van Ommen, G. J.

1990-01-01

We report on 5 brothers with slowly progressive limbgirdle weakness. Calf hypertrophy was absent. The levels of creatine kinase, electromyography, and findings from a muscle biopsy specimen were compatible with muscular dystrophy. The propositus's biopsy specimen also showed numerous rimmed

What Are the Treatments for Muscular Dystrophy?

Science.gov (United States)

... Child Neurology Society. (2005). Practice parameter: Corticosteroid treatment of Duchenne dystrophy. Neurology, 64 , 13-20. Retrieved June 22, 2012, ... Statement. (2004). Respiratory care of the patient with Duchenne muscular ... American Journal of Respiratory and Critical Care Medicine, 170, 456-465. ...

Intramuscular renin-angiotensin system is activated in human muscular dystrophy.

Science.gov (United States)

Sun, Guilian; Haginoya, Kazuhiro; Dai, Hongmei; Chiba, Yoko; Uematsu, Mitsugu; Hino-Fukuyo, Naomi; Onuma, Akira; Iinuma, Kazuie; Tsuchiya, Shigeru

2009-05-15

To investigate the role of the muscular renin-angiotensin system (RAS) in human muscular dystrophy, we used immunohistochemistry and Western blotting to examine the cellular localization of angiotensin-converting enzyme (ACE), the angiotensin II type 1 receptor (AT1) and the angiotensin II type 2 receptor (AT2) in muscle biopsies from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD), and congenital muscular dystrophy (CMD). In normal muscle, ACE was expressed in vascular endothelial cells and neuromuscular junctions (NMJs), whereas AT1 was immunolocalized to the smooth muscle cells of blood vessels and intramuscular nerve twigs. AT2 was immunolocalized in the smooth muscle cells of blood vessels. These findings suggest that the RAS has a functional role in peripheral nerves and NMJs. ACE and AT1, but AT2 immunoreactivity were increased markedly in dystrophic muscle as compared to controls. ACE and the AT1 were strongly expressed in the cytoplasm and nuclei of regenerating muscle fibers, fibroblasts, and in macrophages infiltrating necrotic fibers. Double immunolabeling revealed that activated fibroblasts in the endomysium and perimysium of DMD and CMD muscle were positive for ACE and AT1. Triple immunolabeling demonstrated that transforming growth factor-beta1 (TGF-beta1) and ACE were colocalized on the cytoplasm of activated fibroblasts in dystrophic muscle. Furthermore, Western blotting showed increases in the expression of AT1 and TGF-beta1 protein in dystrophic muscle, which coincided with our immunohistochemical results. The overexpression of ACE and AT1 in dystrophic muscle would likely result in the increased production of Ang II, which may act on these cells in an autocrine manner via AT1. The activation of AT1 may induce fibrous tissue formation through overexpression of TGF-beta1, which potently activates fibrogenesis and suppresses regeneration. In conclusion, our results imply that the intramuscular RAS-TGF-beta1 pathway

[DIAGNOSTIC VARIATIONS OF X-LINKED MUSCULAR DYSTROPHY WITH CONTRACTURES].

Science.gov (United States)

Kvirkvelia, N; Shakarishvili, R; Gugutsidze, D; Khizanishvili, N

2015-01-01

Case report with review describes X-linked muscular dystrophy with contractures in 28 years old man and his cousin. The disease revealed itself in an early stage (age 5-10), the process was progressing with apparent tendons retraction and contraction, limited movement in the areas of the neck and back of spine, atrophy of shoulder and pelvic yard and back muscles. Intellect was intact. Cardyomyopathy was exhibited. CK was normal. EMG showed classic myopathic features. Muscle biopsy showed different caliber groups of muscle fibers, growth of endo-perimesial connective tissue. Clinical manifestations together with electrophysiological and histological data suggest consistency with Rotthauwe-Mortier-Bayer X-linked muscular dystrophy.

Temporalis muscle hypertrophy and reduced skull eccentricity in Duchenne muscular dystrophy.

Science.gov (United States)

Straathof, C S M; Doorenweerd, N; Wokke, B H A; Dumas, E M; van den Bergen, J C; van Buchem, M A; Hendriksen, J G M; Verschuuren, J J G M; Kan, H E

2014-10-01

Muscle hypertrophy and muscle weakness are well known in Duchenne muscular dystrophy. Decreased muscle force can have secondary effects on skeletal growth and development such as facial and dental morphology changes. In this study, we quantified temporal muscle thickness, circumference, and eccentricity of the skull and the head on T1-weighted magnetic resonance imaging (MRI) scans of the head of 15 Duchenne muscular dystrophy patients and 15 controls. Average temporal muscle thickness was significantly increased in patients (12.9 ± 5.2 mm) compared to controls (6.8 ± 1.4 mm) (P muscle thickness and skull eccentricity were significantly negatively correlated in patients, and positively in controls. Hypertrophy of the temporal muscles and changes in skull eccentricity appear to occur early in the course of Duchenne muscular dystrophy. Further studies in younger patients are needed to confirm a causal relationship. © The Author(s) 2014.

Cardiac function associated with home ventilator care in Duchenne muscular dystrophy.

Science.gov (United States)

Lee, Sangheun; Lee, Heeyoung; Eun, Lucy Youngmin; Gang, Seung Woong

2018-02-01

Cardiomyopathy is becoming the leading cause of death in patients with Duchenne muscular dystrophy because mechanically assisted lung ventilation and assisted coughing have helped resolve respiratory complications. To clarify cardiopulmonary function, we compared cardiac function between the home ventilator-assisted and non-ventilator-assisted groups. We retrospectively reviewed patients with Duchenne muscular dystrophy from January 2010 to March 2016 at Gangnam Severance Hospital. Demographic characteristics, pulmonary function, and echocardiography data were investigated. Fifty-four patients with Duchenne muscular dystrophy were divided into 2 groups: home ventilator-assisted and non-ventilator-assisted. The patients in the home ventilator group were older (16.25±1.85 years) than those in the nonventilator group (14.73±1.36 years) ( P =0.001). Height, weight, and body surface area did not differ significantly between groups. The home ventilator group had a lower seated functional vital capacity (1,038±620.41 mL) than the nonventilator group (1,455±603.12 mL). Mean left ventricular ejection fraction and fractional shortening were greater in the home ventilator group, but the data did not show any statistical difference. The early ventricular filling velocity/late ventricular filling velocity ratio (1.7±0.44) was lower in the home ventilator group than in the nonventilator group (2.02±0.62). The mitral valve annular systolic velocity was higher in the home ventilator group (estimated β, 1.06; standard error, 0.48). Patients with Duchenne muscular dystrophy on a ventilator may have better systolic and diastolic cardiac functions. Noninvasive ventilator assistance can help preserve cardiac function. Therefore, early utilization of noninvasive ventilation or oxygen may positively influence cardiac function in patients with Duchenne muscular dystrophy.

Modulation of Stem Cell Differentiation and Myostatin as an Approach to Counteract Fibrosis in Muscle Dystrophy and Regeneration after Injury

Science.gov (United States)

2011-03-01

Duchenne muscular dystrophy (DMD). To examine whether counteracting myostatin, a negative regulator of muscle mass and a pro-lipofibrotic factor...extracellular matrix, and fat, characterizes muscle dystrophy , and in particular Duchenne muscular dystrophy (DMD) (1,2), as seen also in its animal model...stem cells (MDSC) into myogenic as opposed to lipofibrogenic lineages is a promising therapeutic strategy for Duchenne muscular dystrophy (DMD). To

Cardiomyopathy in becker muscular dystrophy: Overview.

Science.gov (United States)

Ho, Rady; Nguyen, My-Le; Mather, Paul

2016-06-26

Becker muscular dystrophy (BMD) is an X-linked recessive disorder involving mutations of the dystrophin gene. Cardiac involvement in BMD has been described and cardiomyopathy represents the number one cause of death in these patients. In this paper, the pathophysiology, clinical evaluations and management of cardiomyopathy in patients with BMD will be discussed.

Histopathological findings in Becker-type muscular dystrophy

NARCIS (Netherlands)

ten Houten, R.; de Visser, M.

1984-01-01

Muscle biopsy specimens from 14 patients with Becker-type muscular dystrophy were analyzed to investigate possible neurogenic factors underlying the histopathological changes. Group atrophy, pyknotic nuclear clumps, and angular small fibers were seen respectively in 71%, 85%, and 100% of the cases.

Preliminary diffusion tensor imaging studies in limb-girdle muscular dystrophies

Science.gov (United States)

Hidalgo-Tobon, S.; Hernandez-Salazar, G.; Vargas-Cañas, S.; Marrufo-Melendez, O.; Solis-Najera, S.; Taboada-Barajas, J.; Rodriguez, A. O.; Delgado-Hernandez, R.

2012-10-01

Limb-girdle muscular dystrophies (LGMD) are a group of autosomal dominantly or recessively inherited muscular dystrophies that also present with primary proximal (limb-girdle) muscle weakness. This type of dystrophy involves the shoulder and pelvic girdles, distinct phenotypic or clinical characteristics are recognized. Imaging experiments were conducted on a 1.5T GE scanner (General Electric Medical Systems. Milwaukee. USA), using a combination of two eight-channel coil array. Diffusion Tensor Imaging (DTI) data were acquired using a SE-EPI sequence, diffusion weighted gradients were applied along 30 non-collinear directions with a b-value=550 s/mm2. The connective tissue content does not appear to have a significant effect on the directionality of the diffusion, as assessed by fractional anisotropy. The fibers of the Sartorius muscle and gracilis showed decreased number of tracts, secondary to fatty infiltration and replacement of connective tissue and muscle mass loss characteristic of the underlying pathology. Our results demonstrated the utility of non-invasive MRI techniques to characterize the muscle pathology, through quantitative and qualitative methods such as the FA values and tractrography.

Fat embolism after fractures in Duchenne muscular dystrophy: an underdiagnosed complication? A systematic review

Directory of Open Access Journals (Sweden)

Feder D

2017-10-01

Full Text Available David Feder,1 Miriam Eva Koch,1 Beniamino Palmieri,2 Fernando Luiz Affonso Fonseca,1 Alzira Alves de Siqueira Carvalho3 1Pharmacology Department, Faculdade de Medicina do ABC, Santo André, São Paulo, Brazil; 2Department of General Surgery and Surgical Specialties, University of Modena and Reggio Emilia Medical School, Surgical Clinic, Modena, Italy; 3Neuroscience Department, Faculdade de Medicina do ABC, Santo André, São Paulo, Brazil Abstract: Duchenne muscular dystrophy is the most frequent lethal genetic disease. Several clinical trials have established both the beneficial effect of steroids in Duchenne muscular dystrophy and the well-known risk of side effects associated with their daily use. For many years it has been known that steroids associated with ambulation loss lead to obesity and also damage the bone structure resulting in the bone density reduction and increased incidence of bone fractures and fat embolism syndrome, an underdiagnosed complication after fractures. Fat embolism syndrome is characterized by consciousness disturbance, respiratory failure and skin rashes. The use of steroids in Duchenne muscular dystrophy may result in vertebral fractures, even without previous trauma. Approximately 25% of patients with Duchenne muscular dystrophy have a long bone fracture, and 1% to 22% of fractures have a chance to develop fat embolism syndrome. As the patients with Duchenne muscular dystrophy have progressive cardiac and respiratory muscle dysfunction, the fat embolism may be unnoticed clinically and may result in increased risk of death and major complications. Different treatments and prevention measures of fat embolism have been proposed; however, so far, there is no efficient therapy. The prevention, early diagnosis and adequate symptomatic treatment are of paramount importance. The fat embolism syndrome should always be considered in patients with Duchenne muscular dystrophy presenting with fractures, or an unexplained and

Disabilities caused by unstable mutations in Costa Rica

Directory of Open Access Journals (Sweden)

Patricia Cuenca

2004-09-01

Full Text Available La distrofia miotónica tipo1 (DM1 y el síndrome del cromosoma X frágil (FRAXA son dos enfermedades hereditarias relativamente comunes. Ambas constituyen ejemplos de un nuevo tipo de mecanismo mutacional, llamado mutaciones inestables o dinámicas, expansión de tripletas, o amplificación del ADN. La DM1 se considera como la distrofia muscular más frecuente en los adultos y FRAXA es la principal causa de retardo mental hereditario. Este trabajo presenta resultados actualizados de un estudio prospectivo no aleatorio en pacientes clínicamente afectados, que se realiza con el objetivo de confirmar el diagnóstico con técnicas moleculares (Hibridación de Southern y reacción en cadena de la polimerasa, PCR, y llevar a cabo el tamizaje en cascada del resto de la familia para ofrecerles consejo genético adecuado. Se confirmó el diagnóstico clínico inicial en la mayoría de los casos de distrofia miotónica, pero en los casos con retardo mental, más de la mitad de los análisis resultaron negativos para la amplificación en el gen FMR1, específica de FRAXA. La razón principal para esto podría ser el cuadro clínico muy sutil que muestran los niños afectados antes de la pubertad. Los únicos métodos disponibles para prevenir estas discapacidades por el momento son, el tamizaje en cascada, el consejo genético y el aborto selectivo. De los cuales, el último no se puede llevar a cabo según las leyes vigentes en Costa Rica.Myotonic dystrophy and fragile X syndrome are two genetically determined relatively common disabilities. Both are examples of a new type of mutation mechanism called unstable or dynamic mutations, triple repeats expansions or DNA amplification. Fragile X syndrome is recognized as the main cause of hereditary mental retardation and myotonic dystrophy is considered the most common muscular dystrophy of adults. This is a prospective non randomized study of clinically affected people, in order to confirm the diagnosis with

Fracture in Duchenne Muscular Dystrophy: Natural History and Vitamin D Deficiency.

Science.gov (United States)

Perera, Nadia; Sampaio, Hugo; Woodhead, Helen; Farrar, Michelle

2016-08-01

The present study examined the natural history of fracture and vitamin D levels in Duchenne muscular dystrophy patients, who are vulnerable to osteoporosis and fractures. Retrospective analysis of a cohort of 48 Duchenne muscular dystrophy patients revealed that 43% of patients experienced ≥1 fracture. Fracture probabilities at ages 6, 9, 12, and 15 years were 4%, 9%, 31%, and 60% respectively, accelerating around the time of ambulation loss (mean age 11.8 ± 2.7 years). Chronic corticosteroid therapy was utilized in 69% of patients and was associated with all vertebral fractures. A history of vitamin D deficiency occurred in 84%, and 35% were currently deficient. Despite chronic vitamin D supplementation, 38% remained deficient. These results demonstrate that osteoporosis and fracture remain major concerns in Duchenne muscular dystrophy. Bone health should be optimized well before loss of ambulation, however current levels of vitamin D supplementation may be inadequate given high levels of deficiency. © The Author(s) 2016.

NAD+ Biosynthesis Ameliorates a Zebrafish Model of Muscular Dystrophy

Science.gov (United States)

Goody, Michelle F.; Kelly, Meghan W.; Reynolds, Christine J.; Khalil, Andre; Crawford, Bryan D.; Henry, Clarissa A.

2012-01-01

Muscular dystrophies are common, currently incurable diseases. A subset of dystrophies result from genetic disruptions in complexes that attach muscle fibers to their surrounding extracellular matrix microenvironment. Cell-matrix adhesions are exquisite sensors of physiological conditions and mediate responses that allow cells to adapt to changing conditions. Thus, one approach towards finding targets for future therapeutic applications is to identify cell adhesion pathways that mediate these dynamic, adaptive responses in vivo. We find that nicotinamide riboside kinase 2b-mediated NAD+ biosynthesis, which functions as a small molecule agonist of muscle fiber-extracellular matrix adhesion, corrects dystrophic phenotypes in zebrafish lacking either a primary component of the dystrophin-glycoprotein complex or integrin alpha7. Exogenous NAD+ or a vitamin precursor to NAD+ reduces muscle fiber degeneration and results in significantly faster escape responses in dystrophic embryos. Overexpression of paxillin, a cell adhesion protein downstream of NAD+ in this novel cell adhesion pathway, reduces muscle degeneration in zebrafish with intact integrin receptors but does not improve motility. Activation of this pathway significantly increases organization of laminin, a major component of the extracellular matrix basement membrane. Our results indicate that the primary protective effects of NAD+ result from changes to the basement membrane, as a wild-type basement membrane is sufficient to increase resilience of dystrophic muscle fibers to damage. The surprising result that NAD+ supplementation ameliorates dystrophy in dystrophin-glycoprotein complex– or integrin alpha7–deficient zebrafish suggests the existence of an additional laminin receptor complex that anchors muscle fibers to the basement membrane. We find that integrin alpha6 participates in this pathway, but either integrin alpha7 or the dystrophin-glycoprotein complex is required in conjunction with integrin

NAD+ biosynthesis ameliorates a zebrafish model of muscular dystrophy.

Directory of Open Access Journals (Sweden)

Michelle F Goody

Full Text Available Muscular dystrophies are common, currently incurable diseases. A subset of dystrophies result from genetic disruptions in complexes that attach muscle fibers to their surrounding extracellular matrix microenvironment. Cell-matrix adhesions are exquisite sensors of physiological conditions and mediate responses that allow cells to adapt to changing conditions. Thus, one approach towards finding targets for future therapeutic applications is to identify cell adhesion pathways that mediate these dynamic, adaptive responses in vivo. We find that nicotinamide riboside kinase 2b-mediated NAD+ biosynthesis, which functions as a small molecule agonist of muscle fiber-extracellular matrix adhesion, corrects dystrophic phenotypes in zebrafish lacking either a primary component of the dystrophin-glycoprotein complex or integrin alpha7. Exogenous NAD+ or a vitamin precursor to NAD+ reduces muscle fiber degeneration and results in significantly faster escape responses in dystrophic embryos. Overexpression of paxillin, a cell adhesion protein downstream of NAD+ in this novel cell adhesion pathway, reduces muscle degeneration in zebrafish with intact integrin receptors but does not improve motility. Activation of this pathway significantly increases organization of laminin, a major component of the extracellular matrix basement membrane. Our results indicate that the primary protective effects of NAD+ result from changes to the basement membrane, as a wild-type basement membrane is sufficient to increase resilience of dystrophic muscle fibers to damage. The surprising result that NAD+ supplementation ameliorates dystrophy in dystrophin-glycoprotein complex- or integrin alpha7-deficient zebrafish suggests the existence of an additional laminin receptor complex that anchors muscle fibers to the basement membrane. We find that integrin alpha6 participates in this pathway, but either integrin alpha7 or the dystrophin-glycoprotein complex is required in conjunction

Duchenne muscular dystrophy: High-resolution melting curve ...

African Journals Online (AJOL)

Duchenne muscular dystrophy: High-resolution melting curve analysis as an affordable diagnostic mutation scanning tool in a South African cohort. ... Genetic screening for D/BMD in South Africa currently includes multiple ligase-dependent probe amplification (MLPA) for exonic deletions and duplications and linkage ...

Radiographic and ultrasonographic features of hypertrophic feline muscular dystrophy in two cats

International Nuclear Information System (INIS)

Berry, C.R.; Gaschen, F.P.; Ackerman, N.

1992-01-01

Hypertrophic fellne musculer dystrophy has been reported as an X-linked inherited deficiency of a cytoskeletal myofiber protein called dystrophin. This report deserlbes the radiographic and ultrasonographic abnormalities of two male littermate domestic short-hair cats and reviews the previous reported findings assoclated with hypertrophic feline muscular dystrophy. The thoracic radiographic abnormalities included: progressive cardiomegaly, large convex, scalloped irregularities associated with the vetral aspect of the diaphragm, and variable degrees of esophageal dilation (megaesophagus) with associated cranioventral aspiration pneumonia. Echocardiographic features included: concentric left vetricular wall thickening, increased left ventricular and diastolic and systolic dimensions, and an increase in endocardial echogenicity. Abdominal radiographic abnormalities included: hepatosplenomegaly, peritoneal effusion, renomegaly, adrenal gland mineralization, and paralumbar and diaphragmatic musculature enlargement. Abdomlnal ultrasonographic abnormalities included: irregularly thickened muscular portion of the diaphragm; hypoechogenicity of the liver; peritoneal effusion; hepatosplenomegaly; renomegaly with hyperechoic cortex and medulla; and adrenal gland mineralization. The irregular scalloped appearance of the diaphragm (particularly along the ventral/sternal margin) was a consistenl radiographic abnormlity in the two cats with hypertrophic feline muscular dystrophy after the age of 7 months. This finding was confirmed by ultrasound as a thickened irregular, hyperechoic diaphragm. A diagnosis of hypertrophic feline muscular dystrophy should be strongly suspected if this abnormality is identified

Endocrine function in 97 patients with myotonic dystrophy type 1

DEFF Research Database (Denmark)

Ørngreen, Mette Cathrine; Arlien-Søborg, P.; Duno, M

2012-01-01

. Correlation with CTG(n) expansion size was investigated with the Pearson correlation test. Eighteen percent of the DM1 patients had hyperparathyroidism with increased PTH compared with 0.5% in the background population. Of these, 16% had normocalcemia and 2% had hypercalcemia. An additional 3% had...... LH, but normal testosterone levels, indicating relative insufficiency. Numbers of CTG repeats correlated directly with plasma PTH, phosphate, LH, and tended to correlate with plasma testosterone for males. This is the largest study of endocrine dysfunction in a cohort of Caucasian patients with DM1....... We found that patients with DM1 have an increased risk of abnormal endocrine function, particularly calcium metabolism disorders. However, the endocrine dysfunction appears not to be of clinical significance in all of the cases. Finally, we found correlations between CTG(n) expansion size and plasma...

Muscular dystrophies: key elements for everyday diagnosis and management

Directory of Open Access Journals (Sweden)

Alberto Palladino

2013-12-01

Full Text Available Muscular dystrophies are a heterogeneous group of inherited disorders that share similar clinical features and dystrophic changes on muscle biopsy, associated with progressive weakness. Weakness may be noted at birth or develop in late adult life. In recent years, cardiac involvement has been observed in a growing number of genetic muscle diseases, and considerable progress has been made in understanding the relationships between disease skeletal muscle and cardiac muscle disease. This review will focus on the skeletal muscle diseases most commonly associated with cardiac complications that can be diagnosed by echocardiography, such as dystrophinopathies including Duchenne (DMD and Becker (BMD muscular dystrophies, cardiomyopathy of DMD/BMD carriers and X-L dilated cardiomyopathy.

Heme oxygenase and carbon monoxide protect from muscle dystrophy.

Science.gov (United States)

Chan, Mun Chun; Ziegler, Olivia; Liu, Laura; Rowe, Glenn C; Das, Saumya; Otterbein, Leo E; Arany, Zoltan

2016-11-28

Duchenne muscle dystrophy (DMD) is one of the most common lethal genetic diseases of children worldwide and is 100% fatal. Steroids, the only therapy currently available, are marred by poor efficacy and a high side-effect profile. New therapeutic approaches are urgently needed. Here, we leverage PGC-1α, a powerful transcriptional coactivator known to protect against dystrophy in the mdx murine model of DMD, to search for novel mechanisms of protection against dystrophy. We identify heme oxygenase-1 (HO-1) as a potential novel target for the treatment of DMD. Expression of HO-1 is blunted in the muscles from the mdx murine model of DMD, and further reduction of HO-1 by genetic haploinsufficiency worsens muscle damage in mdx mice. Conversely, induction of HO-1 pharmacologically protects against muscle damage. Mechanistically, HO-1 degrades heme into biliverdin, releasing in the process ferrous iron and carbon monoxide (CO). We show that exposure to a safe low dose of CO protects against muscle damage in mdx mice, as does pharmacological treatment with CO-releasing molecules. These data identify HO-1 and CO as novel therapeutic agents for the treatment of DMD. Safety profiles and clinical testing of inhaled CO already exist, underscoring the translational potential of these observations.

Nonmuscular involvement in merosin-negative congenital muscular dystrophy.

NARCIS (Netherlands)

Gilhuis, H.J.; Donkelaar, H.J. ten; Tanke, R.B.; Vingerhoets, D.M.; Zwarts, M.J.; Verrips, A.; Gabreëls, F.J.M.

2002-01-01

The spectrum of nonmuscular involvement in six children with merosin-negative congenital muscular dystrophy is described. In all children, biochemical, neuroradiologic, cardiac, and neurophysiologic studies were performed. Cerebral structures that were myelinated at gestation, including internal

A Drosophila model for Duchenne muscular dystrophy

NARCIS (Netherlands)

Plas, Mariska Cathelijne van der

2008-01-01

Duchenne Muscular Dystrophy (DMD) is a severe X-linked disease characterized by progressive muscle wasting and sometimes mild mental retardation. The disease is caused by mutations in the dystrophin gene. DMD is correlated with the absence of Dp427, which is located along the sarcolemma in skeletal

Cardiac abnormalities in a follow-up study on carriers of Duchenne and Becker muscular dystrophy

NARCIS (Netherlands)

van Westrum, S. M. Schade; Hoogerwaard, E. M.; Dekker, L.; Standaar, T. S.; Bakker, E.; Ippel, P. F.; Oosterwijk, J. C.; Majoor-Krakauer, D. F.; van Essen, A. J.; Leschot, N. J.; Wilde, A. A. M.; de Haan, R. J.; de Visser, M.; van der Kooi, A. J.

Objectives: Cardiac involvement has been reported in carriers of dystrophin mutations giving rise to Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). The progress of these abnormalities during long-term follow-up is unknown. We describe the long-term follow-up of dilated

Cardiac abnormalities in a follow-up study on carriers of Duchenne and Becker muscular dystrophy

NARCIS (Netherlands)

Schade van Westrum, S. M.; Hoogerwaard, E. M.; Dekker, L.; Standaar, T. S.; Bakker, E.; Ippel, P. F.; Oosterwijk, J. C.; Majoor-Krakauer, D. F.; van Essen, A. J.; Leschot, N. J.; Wilde, A. A. M.; de Haan, R. J.; de Visser, M.; van der Kooi, A. J.

2011-01-01

Objectives: Cardiac involvement has been reported in carriers of dystrophin mutations giving rise to Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). The progress of these abnormalities during long-term follow-up is unknown. We describe the long-term follow-up of dilated

Ultrastructural and ERG findings in progressive rod-cone dystrophy in a litter of Labrador retrievers.

Science.gov (United States)

Raitta, C; Kommonen, B; Ulshafer, R; Karhunen, U

1991-02-01

Early ultrastructural findings of a progressive photoreceptor dystrophy and corresponding ERG findings are reported in 3 Labrador Retrievers from a litter of 7 pups bred from 2 dogs clinically and electroretinographically affected with generalized progressive retinal dystrophy. The pups were euthanized at 5, 11 and 15 months post partum. The most prominent ultrastructural finding was photoreceptor dystrophy. At 5 months the outer nuclear layer (ONL) consisted of 8-10 layers and seemed reduced in thickness, pyknotic nuclei were seen in this layer. The receptor outer segments (OS) were short and swollen. Some disorientation of OS discs occurred. In the 11-months specimen 7-8 ONL layers were identified. Overall thinning of the neuro-retina had occurred and fewer receptors compared to the 5-months specimen were present. By 15 months the ONL was further reduced to about 4 layers. Enlarged internuclear spaces were present in the ONL as well as around inner segments (IS). Phagocytic cells were frequent among remains of OS. The pigment epithelium appeared normal. The dark adapted ERG b-wave amplitudes and photopic 30 Hz flicker responses were low in comparison to controls of the same breed, and decreased with age. The condition represents a progressive rod-cone dystrophy which shares similarities with primary receptor dystrophy in man such as retinitis pigmentosa.

A Human Pluripotent Stem Cell Model of Facioscapulohumeral Muscular Dystrophy-Affected Skeletal Muscles.

Science.gov (United States)

Caron, Leslie; Kher, Devaki; Lee, Kian Leong; McKernan, Robert; Dumevska, Biljana; Hidalgo, Alejandro; Li, Jia; Yang, Henry; Main, Heather; Ferri, Giulia; Petek, Lisa M; Poellinger, Lorenz; Miller, Daniel G; Gabellini, Davide; Schmidt, Uli

2016-09-01

: Facioscapulohumeral muscular dystrophy (FSHD) represents a major unmet clinical need arising from the progressive weakness and atrophy of skeletal muscles. The dearth of adequate experimental models has severely hampered our understanding of the disease. To date, no treatment is available for FSHD. Human embryonic stem cells (hESCs) potentially represent a renewable source of skeletal muscle cells (SkMCs) and provide an alternative to invasive patient biopsies. We developed a scalable monolayer system to differentiate hESCs into mature SkMCs within 26 days, without cell sorting or genetic manipulation. Here we show that SkMCs derived from FSHD1-affected hESC lines exclusively express the FSHD pathogenic marker double homeobox 4 and exhibit some of the defects reported in FSHD. FSHD1 myotubes are thinner when compared with unaffected and Becker muscular dystrophy myotubes, and differentially regulate genes involved in cell cycle control, oxidative stress response, and cell adhesion. This cellular model will be a powerful tool for studying FSHD and will ultimately assist in the development of effective treatments for muscular dystrophies. This work describes an efficient and highly scalable monolayer system to differentiate human pluripotent stem cells (hPSCs) into skeletal muscle cells (SkMCs) and demonstrates disease-specific phenotypes in SkMCs derived from both embryonic and induced hPSCs affected with facioscapulohumeral muscular dystrophy. This study represents the first human stem cell-based cellular model for a muscular dystrophy that is suitable for high-throughput screening and drug development. ©AlphaMed Press.

Unusual Respiratory Manifestations in Two Young Adults with Duchenne Muscular Dystrophy

Directory of Open Access Journals (Sweden)

Julie Lemay

2012-01-01

Full Text Available Adult respirologists are often involved in the evaluation and treatment of young adult patients with Duchenne muscular dystrophy. In this context, the most frequent respiratory complication is nocturnal and daytime hypoventilation related to respiratory muscle weakness. The present article describes cases of Duchenne muscular dystrophy involving two brothers, 17 and 19 years of age, respectively, who presented with less frequently reported respiratory complications of their disease: obstructive sleep apnea and Cheyne-Stokes respiration with central apnea, which were believed to be partially or completely related to congestive cardiomyopathy.

[Specific features of Becker Muscular Dystrophy patients and female carriers of Duchenne Muscular Dystrophy].

Science.gov (United States)

Magot, A; Mercier, S; Péréon, Y

2015-12-01

Becker muscular dystrophy (BMD) was first described in 1955 and linked to the DMD gene in 1987. Compared to Duchenne muscular dystrophy (DMD), clinical onset of BMD usually occurs after the age of 12 and wheelchair is required after the age of 16. BMD is characterized by generalized weakness first affecting limb girdle muscles, hypertrophy of the calves and cardiomyopathy in males. Some patients have only mild symptoms such as cramps or elevated serum creatine kinases (SCK) throughout all their lives. SCK levels are usually elevated. Muscle biopsy (immunohistochemistry or immunoblotting) shows a dystrophic pattern with abnormal dystrophin staining. Diagnosis is confirmed by DMD gene sequencing. Deletions or duplications of one or several exons are identified in the majority of cases. A multidisciplinary approach is recommended for the care management of these patients with a particular attention to the cardiomyopathy, which is typically responsible for death but can be prevented by specific treatment. X-linked dilated cardiomyopathies linked to DMD gene are a phenotypic continuum of BMD. Some female carriers of DMD mutations exhibit clinical symptoms of variable severity, often milder and beginning later than in males. The cardiomyopathy is the most frequent feature that should be especially monitored in these patients. Genetic counselling should be systematically proposed. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Becker′s Muscular Dystrophy-A Case Report

Directory of Open Access Journals (Sweden)

Rajendran P

1998-01-01

Full Text Available A case of Becker′s Muscular dystrophy (BMD in a 26-year-old male is reported. Muscle biopsy immunohistochemical staining showed absence of labelling for dystrophin along the sacrolemmal membrane in majority of the fibres. Antibodies to adhalin and merosin showed normal localisation along the sacrolemma.

Composite biomarkers for assessing Duchenne muscular dystrophy: an initial assessment.

Science.gov (United States)

Shklyar, Irina; Pasternak, Amy; Kapur, Kush; Darras, Basil T; Rutkove, Seward B

2015-02-01

Compared with individual parameters, composite biomarkers may provide a more effective means for monitoring disease progression and the effects of therapy in clinical trials than single measures. In this study, we built composite biomarkers for use in Duchenne muscular dystrophy by combining values from two objective measures of disease severity: electrical impedance myography and quantitative ultrasound and evaluating how well they correlated to standard functional measures. Using data from an ongoing study of electrical impedance myography and quantitative ultrasound in 31 Duchenne muscular dystrophy and 26 healthy boys aged 2-14 years, we combined data sets by first creating z scores based on the normal subject data and then using simple mathematical operations (addition and multiplication) to create composite measures. These composite scores were then correlated to age and standard measures of function including the 6-minute walk test, the North Star Ambulatory Assessment, and handheld dynamometry. Combining data sets resulted in stronger correlations with all four outcomes than for either electrical impedance myography or quantitative ultrasound alone in six of eight instances. These improvements reached statistical significance (P Duchenne muscular dystrophy clinical trials is warranted. Copyright © 2015 Elsevier Inc. All rights reserved.

Cardiac Complications of Fukuyama-Type Congenital Muscular Dystrophy

Directory of Open Access Journals (Sweden)

J Gordon Millichap

2006-07-01

Full Text Available The course of left ventricular function was evaluated using M-mode and Doppler echocardiography in 34 patients with Fukuyama-type congenital muscular dystrophy (FCMD, in a study at the Tokyo Women’s Medical University, Tokyo, Japan.

The prevalence of Usher syndrome and other retinal dystrophy-hearing impairment associations.

Science.gov (United States)

Rosenberg, T; Haim, M; Hauch, A M; Parving, A

1997-05-01

The study was undertaken to procure population-based prevalence data on the various types of Usher syndrome and other retinal dystrophy-hearing impairment associations. The medical files on 646 patients with a panretinal pigmentary dystrophy aged 20-49 years derived from the Danish Retinitis Pigmentosa (RP) register were scrutinised. The data were supplemented by a prior investigation on hearing ability in a part of the study population. After exclusion of patients with possibly extrinsic causes of hearing impairments, 118 patients, including 89 cases of Usher syndrome were allocated to one of five clinically defined groups. We calculated the following prevalence rates: Usher syndrome type I: 1.5/100,000, Usher syndrome type II: 2.2/100,000, and Usher syndrome type III: 0.1/100,000 corresponding to a 2:3 ratio between Usher syndrome type I and II. The overall prevalence rate of Usher syndrome was estimated to 5/100,000 in the Danish population, devoid of genetic isolates. The material comprised 11 cases with retinal dystrophy, hearing impairment, and additional syndromic features. Finally, 18 subjects with various retinal dystrophy-hearing impairment associations without syndromic features were identified, corresponding to a prevalence rate of 0.8/100,000. This group had a significant overrepresentation of X-linked RP, including two persons harboring a mutation in the retinitis pigmentosa GTP-ase regulator (RPGR) gene.

Naturally Protected Muscle Phenotypes: Development of Novel Treatment Strategies for Duchenne Muscular Dystrophy

OpenAIRE

Dowling, Paul; Doran, Philip; Lohan, James; Culligan, Kevin; Ohlendieck, Kay

2004-01-01

Primary abnormalities in the dystrophin gene underlie x-linked muscular dystrophy. However, the absence of the dystrophin isoform Dp427 does not necessarily result in a severe dystrophic phenotype in all muscle groups. Distal mdx muscles, namely extraocular and toe fibres, appear to represent a protected phenotype in muscular dystrophy. Thus, a comparative analysis of affected versus naturally protected muscle cells should lead to a greater knowledge of the molecular pathogenes...

Respiratory muscle training in Duchenne muscular dystrophy.

OpenAIRE

Rodillo, E; Noble-Jamieson, C M; Aber, V; Heckmatt, J Z; Muntoni, F; Dubowitz, V

1989-01-01

Twenty two boys with Duchenne muscular dystrophy were entered into a randomised double blind crossover trial to compare respiratory muscle training with a Triflow II inspirometer and 'placebo' training with a mini peak flow meter. Supine posture was associated with significantly impaired lung function, but respiratory muscle training showed no benefit.

Strength training and albuterol in facioscapulohumeral muscular dystrophy

NARCIS (Netherlands)

van der Kooi, EL; Vogels, OJM; van Asseldonk, RJGP; Lindeman, E; Hendriks, JCM; Wohlgemuth, M; van der Maarel, SM; Padberg, GW

2004-01-01

Background: In animals and healthy volunteers beta2-adrenergic agonists increase muscle strength and mass, in particular when combined with strength training. In patients with facioscapulohumeral muscular dystrophy (FSHD) albuterol may exert anabolic effects. The authors evaluated the effect of

Regulatory T cells suppress muscle inflammation and injury in muscular dystrophy

Science.gov (United States)

Villalta, S. Armando; Rosenthal, Wendy; Martinez, Leonel; Kaur, Amanjot; Sparwasser, Tim; Tidball, James G.; Margeta, Marta; Spencer, Melissa J.; Bluestone, Jeffrey A.

2016-01-01

We examined the hypothesis that regulatory T cells (Tregs) modulate muscle injury and inflammation in the mdx mouse model of Duchenne muscular dystrophy (DMD). Although Tregs were largely absent in the muscle of wildtype mice and normal human muscle, they were present in necrotic lesions, displayed an activated phenotype and showed increased expression of interleukin (IL)-10 in dystrophic muscle from mdx mice. Depletion of Tregs exacerbated muscle injury and the severity of muscle inflammation, which was characterized by an enhanced interferon-gamma (IFNγ) response and activation of M1 macrophages. To test the therapeutic value of targeting Tregs in muscular dystrophy, we treated mdx mice with IL-2/anti-IL-2 complexes (IL-2c), and found that Tregs and IL-10 concentrations were increased in muscle, resulting in reduced expression of cyclooygenase-2 and decreased myofiber injury. These findings suggest that Tregs modulate the progression of muscular dystrophy by suppressing type 1 inflammation in muscle associated with muscle fiber injury, and highlight the potential of Treg-modulating agents as therapeutics for DMD. PMID:25320234

A Cross-Sectional Study of School Experiences of Boys with Duchenne and Becker Muscular Dystrophy

Science.gov (United States)

Soim, Aida; Lamb, Molly; Campbell, Kimberly; Pandya, Shree; Peay, Holly; Howard, James F., Jr.; Fox, Deborah

2016-01-01

The objectives of this study were to investigate types of supportive school services received and factors related to provision of these services. We conducted a cross-sectional study to describe the school experience of males with Duchenne and Becker muscular dystrophies. Study subjects were identified through the Muscular Dystrophy Surveillance,…

Prevalence and Characteristics of Chinese Patients With Duchenne and Becker Muscular Dystrophy

Science.gov (United States)

Lo, Ivan F. M.; Cherk, Sharon W. W.; Cheng, Wai Wai; Fung, Eva L. W.; Yeung, Wai Lan; Ngan, Mary; Lee, Wing Cheong; Kwong, Ling; Wong, Suet Na; Ma, Che Kwan; Tai, Shuk Mui; Ng, Grace S. F.; Wu, Shun Ping; Wong, Virginia C. N.

2015-01-01

The aim of this collaborative study on Duchenne muscular dystrophy and Becker muscular dystrophy is to determine the prevalence and to develop data on such patients as a prelude to the development of registry in Hong Kong. Information on clinical and molecular findings, and patient care, was systematically collected in 2011 and 2012 from all Pediatric Neurology Units in Hong Kong. Ninety patients with dystrophinopathy were identified, and 83% has Duchenne muscular dystrophy. The overall prevalence of dystrophinopathy in Hong Kong in 2010 is 1.03 per 10 000 males aged 0 to 24 years. Among the Duchenne group, we observed a higher percentage (40.6%) of point mutations with a lower percentage (45.3%) of exon deletions in our patients when compared with overseas studies. Although we observed similar percentage of Duchenne group received scoliosis surgery, ventilation support, and cardiac treatment when compared with other countries, the percentage (25%) of steroid use is lower. PMID:28503591

Retro-mode imaging and fundus autofluorescence with scanning laser ophthalmoscope of retinal dystrophies

Directory of Open Access Journals (Sweden)

Maurizio Battaglia

2012-05-01

Full Text Available Abstract Background Retinal dystrophies display a considerably wide range of phenotypic variability, which can make diagnosis and clinical staging difficult. The aim of the study is to analyze the contribution of retro-mode imaging (RMI and fundus autofluorescence (FAF to the characterization of retinal dystrophies. Methods Eighteen consecutive patients affected by retinal dystrophies underwent a complete ophthalmological examination, including best corrected visual acuity with ETDRS charts, blue-light fundus autofluorescence, (BL-FAF, near-infrared fundus autofluorescence (NIR-FAF, and RMI. The primary outcome was the identification of abnormal patterns on RMI. The secondary outcome was the correlation with the findings on BL-FAF and NIR-FAF. Results Overall, the main feature of RMI is represented by a pseudo-3D pattern of all the lesions at the posterior pole. More specifically, any accumulation of material within the retina appears as an area of elevation of different shape and size, displaying irregular and darker borders. No precise correlations between RMI, BL-AF, and NIR-AF imaging was found. Conclusions RMI and FAF appear to be useful tools for characterizing retinal dystrophies. Non-invasive diagnostic tools may yield additional information on the clinical setting and the monitoring of the patients.

Visuospatial Attention Disturbance in Duchenne Muscular Dystrophy

Science.gov (United States)

De Moura, Maria Clara Drummond Soares; do Valle, Luiz Eduardo Ribeiro; Resende, Maria Bernadete Dutra; Pinto, Katia Osternack

2010-01-01

Aim: The cognitive deficits present in the Duchenne muscular dystrophy (DMD) are not yet well characterized. Attention, considered to be the brain mechanism responsible for the selection of sensory stimuli, could be disturbed in DMD, contributing, at least partially, to the observed global cognitive deficit. The aim of this study was to…

Duchenne muscular dystrophy models show their age

OpenAIRE

Chamberlain, Jeffrey S.

2010-01-01

The lack of appropriate animal models has hampered efforts to develop therapies for Duchenne muscular dystrophy (DMD). A new mouse model lacking both dystrophin and telomerase (Sacco et al., 2010) closely mimics the pathological progression of human DMD and shows that muscle stem cell activity is a key determinant of disease severity.

Overexpression of Latent TGFβ Binding Protein 4 in Muscle Ameliorates Muscular Dystrophy through Myostatin and TGFβ.

Science.gov (United States)

Lamar, Kay-Marie; Bogdanovich, Sasha; Gardner, Brandon B; Gao, Quan Q; Miller, Tamari; Earley, Judy U; Hadhazy, Michele; Vo, Andy H; Wren, Lisa; Molkentin, Jeffery D; McNally, Elizabeth M

2016-05-01

Latent TGFβ binding proteins (LTBPs) regulate the extracellular availability of latent TGFβ. LTBP4 was identified as a genetic modifier of muscular dystrophy in mice and humans. An in-frame insertion polymorphism in the murine Ltbp4 gene associates with partial protection against muscular dystrophy. In humans, nonsynonymous single nucleotide polymorphisms in LTBP4 associate with prolonged ambulation in Duchenne muscular dystrophy. To better understand LTBP4 and its role in modifying muscular dystrophy, we created transgenic mice overexpressing the protective murine allele of LTBP4 specifically in mature myofibers using the human skeletal actin promoter. Overexpression of LTBP4 protein was associated with increased muscle mass and proportionally increased strength compared to age-matched controls. In order to assess the effects of LTBP4 in muscular dystrophy, LTBP4 overexpressing mice were bred to mdx mice, a model of Duchenne muscular dystrophy. In this model, increased LTBP4 led to greater muscle mass with proportionally increased strength, and decreased fibrosis. The increase in muscle mass and reduction in fibrosis were similar to what occurs when myostatin, a related TGFβ family member and negative regulator of muscle mass, was deleted in mdx mice. Supporting this, we found that myostatin forms a complex with LTBP4 and that overexpression of LTBP4 led to a decrease in myostatin levels. LTBP4 also interacted with TGFβ and GDF11, a protein highly related to myostatin. These data identify LTBP4 as a multi-TGFβ family ligand binding protein with the capacity to modify muscle disease through overexpression.

Overexpression of Latent TGFβ Binding Protein 4 in Muscle Ameliorates Muscular Dystrophy through Myostatin and TGFβ.

Directory of Open Access Journals (Sweden)

Kay-Marie Lamar

2016-05-01

Full Text Available Latent TGFβ binding proteins (LTBPs regulate the extracellular availability of latent TGFβ. LTBP4 was identified as a genetic modifier of muscular dystrophy in mice and humans. An in-frame insertion polymorphism in the murine Ltbp4 gene associates with partial protection against muscular dystrophy. In humans, nonsynonymous single nucleotide polymorphisms in LTBP4 associate with prolonged ambulation in Duchenne muscular dystrophy. To better understand LTBP4 and its role in modifying muscular dystrophy, we created transgenic mice overexpressing the protective murine allele of LTBP4 specifically in mature myofibers using the human skeletal actin promoter. Overexpression of LTBP4 protein was associated with increased muscle mass and proportionally increased strength compared to age-matched controls. In order to assess the effects of LTBP4 in muscular dystrophy, LTBP4 overexpressing mice were bred to mdx mice, a model of Duchenne muscular dystrophy. In this model, increased LTBP4 led to greater muscle mass with proportionally increased strength, and decreased fibrosis. The increase in muscle mass and reduction in fibrosis were similar to what occurs when myostatin, a related TGFβ family member and negative regulator of muscle mass, was deleted in mdx mice. Supporting this, we found that myostatin forms a complex with LTBP4 and that overexpression of LTBP4 led to a decrease in myostatin levels. LTBP4 also interacted with TGFβ and GDF11, a protein highly related to myostatin. These data identify LTBP4 as a multi-TGFβ family ligand binding protein with the capacity to modify muscle disease through overexpression.

Quality of life of adult men with Duchenne muscular dystrophy in the Netherlands : Implications for care

NARCIS (Netherlands)

Pangalila, Robert F.; Van Den Bos, Geertrudis A M; Bartels, Bart; Bergen, Michael P.; Kampelmacher, Mike J.; Stam, Henk J.; Roebroeck, Marij E.

2015-01-01

Objective: To assess quality of life of adults with Duchenne muscular dystrophy in the Netherlands and to identify domains and major problems influencing quality of life. Design: Cross-sectional. Subjects: Seventy-nine men aged ≥ 20 years with Duchenne muscular dystrophy. Methods: The Medical

A bedside measure of body composition in Duchenne muscular dystrophy.

Science.gov (United States)

Elliott, Sarah A; Davidson, Zoe E; Davies, Peter S W; Truby, Helen

2015-01-01

In clinical practice, monitoring body composition is a critical component of nutritional assessment and weight management in boys with Duchenne muscular dystrophy. We aimed to evaluate the accuracy of a simple bedside measurement tool for body composition, namely bioelectrical impedance analysis, in boys with Duchenne muscular dystrophy. Measures of fat-free mass were determined using a bioelectrical impedance analysis machine and compared against estimations obtained from a reference body composition model. Additionally, the use of raw impedance values was analyzed using three existing predictive equations for the estimation of fat-free mass. Accuracy of bioelectrical impedance analysis was assessed by comparison against the reference model by calculation of biases and limits of agreement. Body composition was measured in 10 boys with Duchenne muscular dystrophy, mean age 9.01 ± 2.34 years. The bioelectrical impedance analysis machine values of fat-free mass were on average 2.3 ± 14.1 kg higher than reference values. Limits of agreement (based on 95% confidence interval of the mean) were -7.4 to 2.9 kg. There was a significant correlation between the mean fat-free mass and difference in fat-free mass between the bioelectrical impedance analysis machine and the reference model (r = -0.86; P = 0.02) suggesting that the bias was not consistent across the range of measurements. The most accurate predictive equation for the estimation of fat-free mass using raw impedance values was the equation by Pietrobelli et al. (mean difference, -0.7 kg; 95% limits of agreement, -3.5 to 2.0 kg). In a clinical setting, where a rapid assessment of body composition is advantageous, the use of raw impedance values, combined with the equation by Pietrobelli et al., is recommended for the accurate estimation of fat-free mass, in boys with Duchenne muscular dystrophy. Copyright © 2015 Elsevier Inc. All rights reserved.

Peripheral nerve blocks as the sole anesthetic technique in a patient with severe Duchenne muscular dystrophy.

Science.gov (United States)

Bang, Seung Uk; Kim, Yee Suk; Kwon, Woo Jin; Lee, Sang Mook; Kim, Soo Hyang

2016-04-01

General anesthesia and central neuraxial blockades in patients with severe Duchenne muscular dystrophy are associated with high risks of complications, including rhabdomyolysis, malignant hyperthermia, hemodynamic instability, and postoperative mechanical ventilation. Here, we describe peripheral nerve blocks as a safe approach to anesthesia in a patient with severe Duchenne muscular dystrophy who was scheduled to undergo surgery. A 22-year-old male patient was scheduled to undergo reduction and internal fixation of a left distal femur fracture. He had been diagnosed with Duchenne muscular dystrophy at 5 years of age, and had no locomotive capability except for that of the finger flexors and toe extensors. He had developed symptoms associated with dyspnea 5 years before and required intermittent ventilation. We blocked the femoral nerve, lateral femoral cutaneous nerve, and parasacral plexus under ultrasound on the left leg. The patient underwent a successful operation using peripheral nerve blocks with no complications. In conclusion general anesthesia and central neuraxial blockades in patients with severe Duchenne muscular dystrophy are unsafe approaches to anesthesia because of hemodynamic instability and respiratory depression. Peripheral nerve blocks are the best way to reduce the risks of critical complications, and are a safe and feasible approach to anesthesia in patients with severe Duchenne muscular dystrophy.

Exon Deletion Pattern in Duchene Muscular Dystrophy in North West of Iran

OpenAIRE

BARZEGAR, Mohammad; HABIBI, Parinaz; BONYADY, Mortaza; TOPCHIZADEH, Vahideh; SHIVA, Shadi

2015-01-01

How to Cite This Article: Barzegar M, Habibi P, Bonyady M, Topchizadeh V, Shiva Sh. Exon Deletion Pattern in Duchene Muscular Dystrophy in North West of Iran. Iran J Child Neurol. 2015 Winter; 9(1): 42-48.AbstractObjectiveDuchene and Becker Muscular Dystrophy (DMD/ BMD) are x-linked disorders that both are the result of heterogeneous mutations in the dystrophin gene. The frequency and distribution of dystrophin gene deletions in DMD/ BMD patients show different patterns among different popula...

The new frontier in muscular dystrophy research: booster genes

DEFF Research Database (Denmark)

Engvall, Eva; Wewer, Ulla M

2003-01-01

More than 30 different forms of muscular dystrophy (MD) have been molecularly characterized and can be diagnosed, but progress toward treatment has been slow. Gene replacement therapy has met with great difficulty because of the large size of the defective genes and because of difficulties...... of the boosters are better understood, drugs may be developed to provide the boost to muscle. Some of the experiences in models of muscular dystrophy may inspire new approaches in other genetic degenerative diseases as well....... in delivering a gene to all muscle groups. Cell replacement therapy has also been difficult to realize. Will it even be possible to design specific therapy protocols for all MDs? Or is a more realistic goal to treat some of the secondary manifestations that are common to several forms of MD, such as membrane...

Studies on congenital hereditary cataract and microphthalmia of the miniature schnauzer dog.

Science.gov (United States)

Shastry, B S; Reddy, V N

1994-09-30

Hereditary cataract in dogs occurs as an autosomal recessive trait. The opacity is primarily in the lens nucleus and posterior cortex. The affected animals also have other ocular abnormalities such as microphthalmia. To understand the genetic basis of this disorder, we have analyzed leukocyte DNA from affected and normal dogs for possible mutations in the homeobox containing gene and myotonic dystrophy locus. The results show that there are no signs of microdeletion, insertion, point mutation and rearrangements in these loci. Although these observations cannot completely rule out the possibility of point mutations, they suggest that the above loci are unlikely to be associated with the disease.

Next Generation Sequencing approach to molecular diagnosis of Duchenne muscular dystrophy; identification of a novel mutation.

Science.gov (United States)

Ebrahimzadeh-Vesal, Reza; Teymoori, Atieh; Azimi-Nezhad, Mohsen; Hosseini, Forough Sadat

2018-02-20

Duchenne Muscular Dystrophy (DMD; MIM 310200) is one of the most common and severe type of hereditary muscular dystrophies. The disease is caused by mutations in the dystrophin gene. The dystrophin gene is associated with X-linked recessive Duchenne and Becker muscular dystrophy. This disease occurs almost exclusively in males. The clinical symptoms of muscle weakness usually begin at childhood. The main symptoms of this disorder are gradually muscular weakness. The affected patients have inability to standing up and walking. Death is usually due to respiratory infection or cardiomyopathy. In this article, we have reported the discovery of a new nonsense mutation that creates abnormal stop codon in the dystrophin gene. This mutation was detected using Next Generation Sequencing (NGS) technique. The subject was a 17-year-old male with muscular dystrophy that who was suspected of having DMD. He was referred to Hakim medical genetics center of Neyshabur, IRAN. Copyright © 2017. Published by Elsevier B.V.

Mild and severe muscular dystrophy caused by a single {gamma}-sarcoglycan mutation

Energy Technology Data Exchange (ETDEWEB)

McNally, E.M.; Boennemann, C.G.; Lidov, H.G.W. [Brigham and Women`s Hospital, Boston, MA (United States)] [and others

1996-11-01

Autosomal recessive muscular dystrophy is genetically heterogeneous. One form of this disorder, limb-girdle muscular dystrophy type 2C (LGMD 2C), is prevalent in northern Africa and has been shown to be associated with a single mutation in the gene encoding the dystrophin-associated protein {gamma}-sarcoglycan. The previous mutation analysis of {gamma}-sarcoglycan required the availability of muscle biopsies. To establish a mutation assay for genomic DNA, the intron-exon structure of the {gamma}-sarcoglycan gene was determined, and primers were designed to amplify each of the exons encoding {gamma}-sarcoglycan. We studied a group of Brazilian muscular dystrophy patients for mutations in the {gamma}-sarcoglycan gene. These patients were selected on the basis of autosomal inheritance and/or the presence of normal dystrophin and/or deficiency of {alpha}-sarcoglycan immunostaining. Four of 19 patients surveyed had a single, homozygous mutation in the {gamma}-sarcoglycan gene. The mutation identified in these patients, all of African-Brazilian descent, is identical to that seen in the North African population, suggesting that even patients of remote African descent may carry this mutation. The phenotype in these patients varied considerably. Of four families with an identical mutation, three have a severe Duchenne-like muscular dystrophy. However, one family has much milder symptoms, suggesting that other loci may be present that modify the severity of the clinical course resulting from {gamma}-sarcoglycan gene mutations. 19 refs., 5 figs., 3 tabs.

Sarcospan Regulates Cardiac Isoproterenol Response and Prevents Duchenne Muscular Dystrophy-Associated Cardiomyopathy.

Science.gov (United States)

Parvatiyar, Michelle S; Marshall, Jamie L; Nguyen, Reginald T; Jordan, Maria C; Richardson, Vanitra A; Roos, Kenneth P; Crosbie-Watson, Rachelle H

2015-12-23

Duchenne muscular dystrophy is a fatal cardiac and skeletal muscle disease resulting from mutations in the dystrophin gene. We have previously demonstrated that a dystrophin-associated protein, sarcospan (SSPN), ameliorated Duchenne muscular dystrophy skeletal muscle degeneration by activating compensatory pathways that regulate muscle cell adhesion (laminin-binding) to the extracellular matrix. Conversely, loss of SSPN destabilized skeletal muscle adhesion, hampered muscle regeneration, and reduced force properties. Given the importance of SSPN to skeletal muscle, we investigated the consequences of SSPN ablation in cardiac muscle and determined whether overexpression of SSPN into mdx mice ameliorates cardiac disease symptoms associated with Duchenne muscular dystrophy cardiomyopathy. SSPN-null mice exhibited cardiac enlargement, exacerbated cardiomyocyte hypertrophy, and increased fibrosis in response to β-adrenergic challenge (isoproterenol; 0.8 mg/day per 2 weeks). Biochemical analysis of SSPN-null cardiac muscle revealed reduced sarcolemma localization of many proteins with a known role in cardiomyopathy pathogenesis: dystrophin, the sarcoglycans (α-, δ-, and γ-subunits), and β1D integrin. Transgenic overexpression of SSPN in Duchenne muscular dystrophy mice (mdx(TG)) improved cardiomyofiber cell adhesion, sarcolemma integrity, cardiac functional parameters, as well as increased expression of compensatory transmembrane proteins that mediate attachment to the extracellular matrix. SSPN regulates sarcolemmal expression of laminin-binding complexes that are critical to cardiac muscle function and protects against transient and chronic injury, including inherited cardiomyopathy. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Bethlem myopathy is not allelic to limb-girdle muscular dystrophy type 1A

Energy Technology Data Exchange (ETDEWEB)

Speer, M.C.; Yamaoka, L.H.; Stajich, J.; Lewis, K. [and others

1995-08-28

The Bethlem myopathy, an autosomal-dominant myopathy, shows a distribution of proximal muscle weakness similar to that observed in dominant limb-girdle muscular dystrophy (LGMD). Yet the Bethlem myopathy differs from most limb-girdle dystrophies in two important regards. First, the Bethlem myopathy presents with joint contractures most commonly observed at the elbows, ankles, and neck. Secondly, disease onset in the Bethlem myopathy is in early childhood, while most dominant LGMDs present with adult onset. 6 refs., 1 fig.

Evidence for linkage disequilibrium in chromosome 13-linked Duchenne-like muscular dystrophy

Energy Technology Data Exchange (ETDEWEB)

Othmane, K.B.; Speer, M.C.; Stauffer, J. [Duke Univ. Medical Center, Durham, NC (United States)] [and others

1995-09-01

Duchenne-like muscular dystrophy (DLMD) is an autosomal recessive Limb Girdle muscular dystrophy (LGMD2C) characterized by late age of onset, proximal muscle weakness leading to disability, high creatine kinase values, normal intelligence and normal dystrophin in muscle biopsy. We have shown previously that three DLMD families from Tunisia are linked to chromosome 13q12. To further localize the LGMD2C gene, we have investigated seven additional families (119 individuals). Both genotyping and two-point linkage analysis were performed as described elsewhere. 7 refs., 1 fig., 1 tab.

Advances in gene therapy for muscular dystrophies [version 1; referees: 2 approved

Directory of Open Access Journals (Sweden)

Hayder Abdul-Razak

2016-08-01

Full Text Available Duchenne muscular dystrophy (DMD is a recessive lethal inherited muscular dystrophy caused by mutations in the gene encoding dystrophin, a protein required for muscle fibre integrity. So far, many approaches have been tested from the traditional gene addition to newer advanced approaches based on manipulation of the cellular machinery either at the gene transcription, mRNA processing or translation levels. Unfortunately, despite all these efforts, no efficient treatments for DMD are currently available. In this review, we highlight the most advanced therapeutic strategies under investigation as potential DMD treatments.

Modulation of Stem Cells Differentiation and Myostatin as an approach to Counteract fibrosis in Muscle Dystrophy and Regeneration after Injury

Science.gov (United States)

2010-03-01

Duchenne muscular dystrophy (DMD), hampers cell therapy in the muscle , and is a feasible therapeutic target. Myostatin (Mst), a...17 Figure 18 Figure 19 Figure 20 Figure 21 • Muscle lipofibrotic degeneration characterizes Duchenne muscular dystrophy (DMD), hampers cell therapy...SUBJECT TERMS Myostatin, muscle dystrophy , stem cells, myogenesis, Oct-4; Duchenne 16. SECURITY CLASSIFICATION OF: U 17. LIMITATION OF ABSTRACT

Swallow Characteristics in Patients with Oculopharyngeal Muscular Dystrophy

Science.gov (United States)

Palmer, Phyllis M.; Neel, Amy T.; Sprouls, Gwyneth; Morrison, Leslie

2010-01-01

Purpose: This prospective investigation evaluates oral weakness and its impact on swallow function, weight, and quality of life in patients with oculopharyngeal muscular dystrophy (OPMD). Method: Intraoral pressure, swallow pressure, and endurance were measured using an Iowa Oral Performance Instrument in participants with OPMD and matched…

Macular pattern dystrophy and homonymous hemianopia in MELAS syndrome.

Science.gov (United States)

Kamal-Salah, Radua; Baquero-Aranda, Isabel; Grana-Pérez, María Del Mar; García-Campos, Jose Manuel

2015-03-12

We report an unusual association of a pattern dystrophy of the retinal pigment epithelium and homonymous hemianopia in a woman diagnosed with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes syndrome. 2015 BMJ Publishing Group Ltd.

Neuroaxonal Dystrophy and Cavitating Leukoencephalopathy of Chihuahua Dogs.

Science.gov (United States)

Degl'Innocenti, Sara; Asiag, Nimrod; Zeira, Offer; Falzone, Cristian; Cantile, Carlo

2017-09-01

A novel form of neuroaxonal dystrophy is described in 3 Chihuahua pups, 2 of which were from the same litter. It was characterized not only by accumulation of numerous and widely distributed axonal swellings (spheroids) but also by a severe cavitating leukoencephalopathy. The dogs presented with progressive neurological signs, including gait abnormalities and postural reaction deficits. Magnetic resonance images and gross examination at necropsy revealed dilation of lateral ventricles and cerebral atrophy, accompanied by cavitation of the subcortical white matter. Histopathologically, severe axonal degeneration with formation of large spheroids was found in the cerebral and cerebellar white matter, thalamus, and brainstem nuclei. Small-caliber spheroids were observed in the cerebral and cerebellar gray matter. The telencephalic white matter had severe myelin loss and cavitation with relative sparing of the U-fibers. Different from previously reported cases of canine neuroaxonal dystrophy, in these Chihuahuas the spheroid distribution predominantly involved the white matter with secondary severe leukoencephalopathy.

Vps35-deficiency impairs SLC4A11 trafficking and promotes corneal dystrophy.

Directory of Open Access Journals (Sweden)

Wei Liu

Full Text Available Vps35 (vacuolar protein sorting 35 is a major component of retromer that selectively promotes endosome-to-Golgi retrieval of transmembrane proteins. Dysfunction of retromer is a risk factor for the pathogenesis of Parkinson's disease (PD and Alzheimer's disease (AD. However, Vps35/retromer's function in the eye or the contribution of Vps35-deficiency to eye degenerative disorders remains to be explored. Here we provide evidence for a critical role of Vps35 in mouse corneal dystrophy. Vps35 is expressed in mouse and human cornea. Mouse cornea from Vps35 heterozygotes (Vps35+/- show features of dystrophy, such as loss of both endothelial and epithelial cell densities, disorganizations of endothelial, stroma, and epithelial cells, excrescences in the Descemet membrane, and corneal edema. Additionally, corneal epithelial cell proliferation was reduced in Vps35-deficient mice. Intriguingly, cell surface targeting of SLC4A11, a membrane transport protein (OH- /H+ /NH3 /H2O of corneal endothelium, whose mutations have been identified in patients with corneal dystrophy, was impaired in Vps35-deficient cells and cornea. Taken together, these results suggest that SLC4A11 appears to be a Vps35/retromer cargo, and Vps35-regulation of SLC4A11 trafficking may underlie Vps35/retromer regulation of corneal dystrophy.

Physical Activity in Boys With Duchenne Muscular Dystrophy Is Lower and Less Demanding Compared to Healthy Boys

NARCIS (Netherlands)

Heutinck, L.B.; Kampen, N. van; Jansen, M.; Groot, I.J.M. de

2017-01-01

This study describes the amount of physical activity and perception of physical activity in boys with Duchenne muscular dystrophy (DMD) compared to healthy boys. A questionnaire described 6 domains of physical activity. Four Duchenne muscular dystrophy subgroups were made: early and late ambulatory,

Fighting against disuse of the masticatory system in duchenne muscular dystrophy : A pilot study using chewing gum

NARCIS (Netherlands)

Van Bruggen, H. Willemijn; Van Den Engel-Hoek, Lenie; Steenks, Michel H.; Van Der Bilt, Andries; Bronkhorst, Ewald M.; Creugers, Nico H J; De Groot, Imelda J M; Kalaykova, Stanimira I.

2015-01-01

Duchenne muscular dystrophy patients report masticatory problems. The aim was to determine the efficacy of mastication training in Duchenne muscular dystrophy using chewing gum for 4 weeks. In all, 17 patients and 17 healthy age-matched males participated. The masticatory performance was assessed

Contractile properties are disrupted in Becker muscular dystrophy, but not in limb girdle type 2I

DEFF Research Database (Denmark)

Løkken, Nicoline; Hedermann, Gitte; Thomsen, Carsten

2016-01-01

We investigated whether a linear relationship between muscle strength and cross-sectional area (CSA) is preserved in calf muscles of patients with Becker muscular dystrophy (BMD, n = 14) and limb-girdle type 2I muscular dystrophy (LGMD2I, n = 11), before and after correcting for muscle fat...

Phenotypic variability in Meesmann's dystrophy

DEFF Research Database (Denmark)

Ehlers, Niels; Hjortdal, Jesper; Nielsen, Kim

2008-01-01

symptoms often include blurred vision and ocular irritation. Typical cases may be entirely free of complaints. Intermittent pain episodes, such as occur in recurrent erosion syndrome, are not the rule. Genetic sequencing indicated a familial relationship with the originally described Meesmann family......'s dystrophy occurs worldwide. The largest family described is the original German one, now supplemented with a Danish branch. Despite the presence of an identical genetic defect, the clinical phenotype varies. This suggests that non-KRT12-related mechanisms are responsible for the variation....

Genetic diagnosis of Duchenne and Becker muscular dystrophy using multiplex ligation-dependent probe amplification in Rwandan patients.

Science.gov (United States)

Uwineza, Annette; Hitayezu, Janvier; Murorunkwere, Seraphine; Ndinkabandi, Janvier; Kalala Malu, Celestin Kaputu; Caberg, Jean Hubert; Dideberg, Vinciane; Bours, Vincent; Mutesa, Leon

2014-04-01

Duchenne and Becker muscular dystrophies are the most common clinical forms of muscular dystrophies. They are genetically X-linked diseases caused by a mutation in the dystrophin (DMD) gene. A genetic diagnosis was carried out in six Rwandan patients presenting a phenotype of Duchenne and Becker muscular dystrophies and six asymptomatic female carrier relatives using multiplex ligation-dependent probe amplification (MLPA). Our results revealed deletion of the exons 48-51 in one patient, an inherited deletion of the exons 8-21 in two brothers and a de novo deletion of the exons 46-50 in the fourth patient. No copy number variation was found in two patients. Only one female carrier presented exon deletion in the DMD gene. This is the first cohort of genetic analysis in Rwandan patients affected by Duchenne and Becker muscular dystrophies. This report confirmed that MLPA assay can be easily implemented in low-income countries.

[New international classification of corneal dystrophies and clinical landmarks].

Science.gov (United States)

Lisch, W; Seitz, B

2008-07-01

The International Committee on Classification of Corneal Dystrophies, briefly IC (3)D, was founded with the sponsorship of the American Cornea Society and the American Academy of Ophthalmology in July 2005. This committee consists of 17 corneal experts (1) from USA, Asia and Europe. The goal of this group was to develop a new, internationally accepted classification of corneal dystrophies (CD) based on modern clinical, histological and genetical knowledge. The aim of the new classification should be to avoid wrong interpretations and misnomers of the different forms of CD. The IC (3)D extensive manuscript is in press as Supplement publication in the journal "Cornea". The 25 different CD are divided in four categories by clinical and genetical knowledge. Additionally, templates for each type of CD are included. Finally, many typical color slit-lamp photos are presented in the publication together with essential references and current genetical results in tabular form. As members of IC (3)D the authors present a clinical landmark survey of the different corneal dystrophies. The ophthalmologist is the first to examine and to diagnose a new patient with a probable CD at the slit-lamp. Our elaborated table of landmarks is supposed to be a "bridge" for the ophthalmologist to precisely define the corneal opacities of a presumed CD. This "bridge" makes it easier for them to study the IC (3)D Supplement publication and to get more information including adequate differential diagnosis.

Immunological identification of a high molecular weight protein as a condidate for the product of the Duchenne muscular dystrophy gene

Energy Technology Data Exchange (ETDEWEB)

Kao, L.; Krstenansky, J.; Mendell, J.; Rammohan, K.W.; Gruenstein, E. (Univ. of Cincinnati College of Medicine, OH (USA))

1988-06-01

An oligopeptide was synthesized based on translation of the nucleotide sequence of the putative exon region of clone pERT87-25 from the gene for Duchenne muscular dystrophy. Immunization of rabbits with this oligopeptide induced the formation of antibodies directed against a protein present in human, rat, and rabbit skeletal muscle. This protein, which is missing in the skeletal muscle of two patients with Duchenne muscular dystrophy, has a molecular mass of {approx}320-420 kDa and is clearly different from the putative Duchenne muscular dystrophy-related protein nebulin. The data suggest that this 320-420-kDa protein is produced by the Duchenne muscular dystrophy gene.

Immunological identification of a high molecular weight protein as a condidate for the product of the Duchenne muscular dystrophy gene

International Nuclear Information System (INIS)

Kao, L.; Krstenansky, J.; Mendell, J.; Rammohan, K.W.; Gruenstein, E.

1988-01-01

An oligopeptide was synthesized based on translation of the nucleotide sequence of the putative exon region of clone pERT87-25 from the gene for Duchenne muscular dystrophy. Immunization of rabbits with this oligopeptide induced the formation of antibodies directed against a protein present in human, rat, and rabbit skeletal muscle. This protein, which is missing in the skeletal muscle of two patients with Duchenne muscular dystrophy, has a molecular mass of ∼320-420 kDa and is clearly different from the putative Duchenne muscular dystrophy-related protein nebulin. The data suggest that this 320-420-kDa protein is produced by the Duchenne muscular dystrophy gene

Distrofia corneana amorfa posterior: relato de caso Posterior amorphous corneal dystrophy: case report

Directory of Open Access Journals (Sweden)

Lauro Augusto de Oliveira

2006-12-01

Full Text Available O objetivo deste trabalho é alertar o oftalmologista da possibilidade de se deparar com casos raros de distrofias corneanas. Neste caso correlacionamos os achados clínicos da distrofia amorfa posterior com refração, topografia e biomicroscopia ultra-sônica.The purpose of this paper is to warn the ophthalmologist about the possibility of facing rare cases of corneal dystrophies. Clinical findings of a case of posterior amorphous dystrophy were correlated with refraction, topography, and ultrasound biomicroscopy.

The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy

Science.gov (United States)

Marshall, Jamie L.; Kwok, Yukwah; McMorran, Brian; Baum, Linda G.; Crosbie-Watson, Rachelle H.

2013-01-01

Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important therapeutic target. Here, we review current protein replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic. PMID:23601082

Distrofia corneana policromática posterior Polychromatic posterior corneal dystrophy

Directory of Open Access Journals (Sweden)

Patrick Frensel de Moraes Tzelikis

2007-08-01

Full Text Available Os autores descrevem quatro raros casos de distrofia corneana policromática posterior, ainda não descrito na literatura nacional. Observam-se opacidades puntiformes, policromáticas, de tamanho uniforme, localização estromal profunda, distribuídas de limbo a limbo e que não interferem na acuidade visual. É apresentada uma revisão dos casos de distrofia pré-Descemet existentes na literatura.The authors describe four rare cases of polychromatic posterior corneal dystrophy, not describe in national literature. The opacities are deep in the stroma, dotlike, polychromatic, uniform in size, distributed from limbus to limbus, leading no reduction in visual acuity. It is also presented a bibliographic review of pre-Descemet's dystrophy.

Corneal stromal dystrophies: a clinical pathologic study Distrofia corneana estromal: um estudo clínicopatológico

Directory of Open Access Journals (Sweden)

Elvira Barbosa Abreu

2012-12-01

Full Text Available INTRODUCTION: Corneal dystrophy is defined as bilateral and symmetric primary corneal disease, without previous associated ocular inflammation. Corneal dystrophies are classified according to the involved corneal layer in superficial, stromal, and posterior dystrophy. Incidence of each dystrophy varies according to the geographic region studied. PURPOSE: To evaluate the prevalence of stromal corneal dystrophies among corneal buttons specimens obtained by penetrating keratoplasty (PK in an ocular pathology laboratory and to correlate the diagnosis with patient age and gender. METHODS: Corneal button cases of penetrating keratoplasty from January-1996 to May-2009 were retrieved from the archives of The Henry C. Witelson Ophthalmic Pathology Laboratory and Registry, Montreal, Canada. The cases with histopathological diagnosis of stromal corneal dystrophies were stained with special stains (Peroxid acid Schiff, Masson trichrome, Congo red analyzed under polarized light, and alcian blue for classification and correlated with epidemiological information (age at time of PK and gender from patients' file. RESULTS: 1,300 corneal buttons cases with clinical diagnose of corneal dystrophy were retrieved. Stromal corneal dystrophy was found in 40 (3.1% cases. Lattice corneal dystrophy was the most prevalent with 26 cases (65%. Nineteen were female (73.07% and the PK was performed at average age of 59.3 years old. Combined corneal dystrophy was found in 8 (20% cases, 5 (62.5% of them were female and the average age of the penetrating keratoplasty was 54.8 years old. Granular corneal dystrophy was represented by 5 (12.5% cases, and 2 (40% of them were female. Penetrating keratoplasty was performed at average age of 39.5 years old in granular corneal dystrophy cases. Macular corneal dystrophy was present in only 1 (2.5% case, in a 36 years old female. CONCLUSION: Systematic histopathological approach and evaluation, including special stains in all stromal

The Duchenne muscular dystrophy population in Denmark, 1977-2001: prevalence, incidence and survival in relation to the introduction of ventilator use

DEFF Research Database (Denmark)

Jeppesen, J; Green, A; Steffensen, B.F.

2003-01-01

Mechanical ventilation of patients with Duchenne muscular dystrophy continues to be a subject of study. The purpose was to estimate prevalence, incidence, mortality and use of mechanical ventilation in the total Duchenne muscular dystrophy population in Denmark between 1977 and 2001 and further....... While overall incidence remained stable at 2.0 per 105, prevalence rose from 3.1 to 5.5 per 105, mortality fell from 4.7 to 2.6 per 100 years at risk and prevalence of Duchenne muscular dystrophy ventilator users rose from 0.9 to 43.4 per 100. We conclude that survival of Duchenne muscular dystrophy...

Reliability of kinetic visual field testing in children with mutation-proven retinal dystrophies: Implications for therapeutic clinical trials.

Science.gov (United States)

Dedania, Vaidehi S; Liu, Jerry Y; Schlegel, Dana; Andrews, Chris A; Branham, Kari; Khan, Naheed W; Musch, David C; Heckenlively, John R; Jayasundera, K Thiran

2018-01-01

Kinetic visual field testing is used to monitor disease course in retinal dystrophy clinical care and treatment response in treatment trials, which are increasingly recruiting children. This study investigates Goldmann visual field (GVF) changes in young children with mutation-proven retinal dystrophies as they age and with progression of the retinal degeneration. Retrospective review of children ≤ 17 years old with a mutation-proven retinal dystrophy. Objective clinical disease activity was assessed by a retinal degeneration specialist masked to GVF results. Digital quantification of GVF area was performed. Twenty-nine children (58 eyes), ages 5-16, were identified. GVF area increased with age despite progression in 20 children and clinical stability in nine children. Mean ± standard error increase in GVF area/year was 333 ± 130 mm 2 (I4e, p = 0.012), 720 ± 155 mm 2 (III4e, p children with mutation-proven retinal dystrophies, there is a significant increase in GVF area with age, particularly those children with retinal dystrophies can be an unreliable measure of response to treatment and on which to base appropriate counseling about visual impairment.

Predictive factors for masticatory performance in Duchenne muscular dystrophy

NARCIS (Netherlands)

Bruggen, H.W. van; Engel-Hoek, L. van den; Steenks, M.H.; Bronkhorst, E.M.; Creugers, N.H.; Groot, I.J.M. de; Kalaykova, S.

2014-01-01

Patients with Duchenne muscular dystrophy (DMD) report masticatory and swallowing problems. Such problems may cause complications such as choking, and feeling of food sticking in the throat. We investigated whether masticatory performance in DMD is objectively impaired, and explored predictive

Functional changes in Becker muscular dystrophy: implications for clinical trials in dystrophinopathies.

Science.gov (United States)

Bello, Luca; Campadello, Paola; Barp, Andrea; Fanin, Marina; Semplicini, Claudio; Sorarù, Gianni; Caumo, Luca; Calore, Chiara; Angelini, Corrado; Pegoraro, Elena

2016-09-01

We performed a 1-year longitudinal study of Six Minute Walk Test (6MWT), North Star Ambulatory Assessment (NSAA), and timed function tests in Becker muscular dystrophy (BMD). Skeletal muscle dystrophin was quantified by immunoblot. We grouped deletions ending on exon 45 ("del 45-x", n = 28) or 51 ("del x-51", n = 10); isolated exon 48 deletion ("del 48", n = 10); and other mutations (n = 21). Only patients in the "del 45-x" or "other" groups became non-ambulatory (n = 5, log-rank p = n.s.) or unable to run (n = 22, p dystrophy.

A new chart for weight control in Duchenne muscular dystrophy.

OpenAIRE

Griffiths, R D; Edwards, R H

1988-01-01

Weight control is desirable in the muscle wasting conditions. A new chart is presented to allow the prediction of an ideal weight, free of excess fat, specifically for boys with Duchenne muscular dystrophy.

Muscle MRI findings in facioscapulohumeral muscular dystrophy

Energy Technology Data Exchange (ETDEWEB)

Gerevini, Simonetta; Caliendo, Giandomenico; Falini, Andrea [IRCCS San Raffaele Scientific Institute, Neuroradiology Unit, Head and Neck Department, Milan (Italy); Scarlato, Marina; Previtali, Stefano Carlo [IRCCS San Raffaele Scientific Institute, Department of Neurology, INSPE and Division of Neuroscience, Milan (Italy); Maggi, Lorenzo; Pasanisi, Barbara; Morandi, Lucia [Fondazione IRCCS Istituto Neurologico ' ' Carlo Besta' ' , Neuromuscular Diseases and Neuroimmunology Unit, Milan (Italy); Cava, Mariangela [IRCCS San Raffaele Scientific Institute, Department of Radiology and Center for Experimental Imaging, Milan (Italy)

2016-03-15

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by extremely variable degrees of facial, scapular and lower limb muscle involvement. Clinical and genetic determination can be difficult, as molecular analysis is not always definitive, and other similar muscle disorders may have overlapping clinical manifestations. Whole-body muscle MRI examination for fat infiltration, atrophy and oedema was performed to identify specific patterns of muscle involvement in FSHD patients (30 subjects), and compared to a group of control patients (23) affected by other myopathies (NFSHD). In FSHD patients, we detected a specific pattern of muscle fatty replacement and atrophy, particularly in upper girdle muscles. The most frequently affected muscles, including paucisymptomatic and severely affected FSHD patients, were trapezius, teres major and serratus anterior. Moreover, asymmetric muscle involvement was significantly higher in FSHD as compared to NFSHD patients. In conclusion, muscle MRI is very sensitive for identifying a specific pattern of involvement in FSHD patients and in detecting selective muscle involvement of non-clinically testable muscles. Muscle MRI constitutes a reliable tool for differentiating FSHD from other muscular dystrophies to direct diagnostic molecular analysis, as well as to investigate FSHD natural history and follow-up of the disease. (orig.)

The potential of sarcospan in adhesion complex replacement therapeutics for the treatment of muscular dystrophy.

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Marshall, Jamie L; Kwok, Yukwah; McMorran, Brian J; Baum, Linda G; Crosbie-Watson, Rachelle H

2013-09-01

Three adhesion complexes span the sarcolemma and facilitate critical connections between the extracellular matrix and the actin cytoskeleton: the dystrophin- and utrophin-glycoprotein complexes and α7β1 integrin. Loss of individual protein components results in a loss of the entire protein complex and muscular dystrophy. Muscular dystrophy is a progressive, lethal wasting disease characterized by repetitive cycles of myofiber degeneration and regeneration. Protein-replacement therapy offers a promising approach for the treatment of muscular dystrophy. Recently, we demonstrated that sarcospan facilitates protein-protein interactions amongst the adhesion complexes and is an important potential therapeutic target. Here, we review current protein-replacement strategies, discuss the potential benefits of sarcospan expression, and identify important experiments that must be addressed for sarcospan to move to the clinic. © 2013 FEBS.

Serum Osteopontin as a Novel Biomarker for Muscle Regeneration in Duchenne Muscular Dystrophy.

Science.gov (United States)

Kuraoka, Mutsuki; Kimura, En; Nagata, Tetsuya; Okada, Takashi; Aoki, Yoshitsugu; Tachimori, Hisateru; Yonemoto, Naohiro; Imamura, Michihiro; Takeda, Shin'ichi

2016-05-01

Duchenne muscular dystrophy is a lethal X-linked muscle disorder. We have already reported that osteopontin (OPN), an inflammatory cytokine and myogenic factor, is expressed in the early dystrophic phase in canine X-linked muscular dystrophy in Japan, a dystrophic dog model. To further explore the possibility of OPN as a new biomarker for disease activity in Duchenne muscular dystrophy, we monitored serum OPN levels in dystrophic and wild-type dogs at different ages and compared the levels to other serum markers, such as serum creatine kinase, matrix metalloproteinase-9, and tissue inhibitor of metalloproteinase-1. Serum OPN levels in the dystrophic dogs were significantly elevated compared with those in wild-type dogs before and 1 hour after a cesarean section birth and at the age of 3 months. The serum OPN level was significantly correlated with the phenotypic severity of dystrophic dogs at the period corresponding to the onset of muscle weakness, whereas other serum markers including creatine kinase were not. Immunohistologically, OPN was up-regulated in infiltrating macrophages and developmental myosin heavy chain-positive regenerating muscle fibers in the dystrophic dogs, whereas serum OPN was highly elevated. OPN expression was also observed during the synergic muscle regeneration process induced by cardiotoxin injection. In conclusion, OPN is a promising biomarker for muscle regeneration in dystrophic dogs and can be applicable to boys with Duchenne muscular dystrophy. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

The muscular dystrophies associated with central nervous system lesions: a brief review from a standpoint of the localization and function of causative genes.

Science.gov (United States)

Yamamoto, Tomoko; Hiroi, Atsuko; Osawa, Makiko; Shibata, Noriyuki

2014-01-01

The muscular dystrophies have been traditionally classified based mainly on clinical manifestation and mode of inheritance. Owing to the discoveries of causative genes, new terminologies derived from each gene, such as dystrophinopathy, α-dystroglycanopathy, sarcoglycanopathy and fukutinopathy, have also become common. Mutations of each gene may cause several clinical phenotypes. Some muscular dystrophies accompany central nervous system (CNS) lesions, especially in the congenital muscular dystrophies. Cobblestone lissencephaly (type II lissencephaly) is a well-known CNS malformation observed in severe forms of α-dystroglycanopathy. Moreover, CNS involvement has been reported in other muscular dystrophies, such as Duchenne muscular dystrophy. In this review, genes related to the muscular dystrophies associated with CNS lesions are briefly described along with the molecular characteristics of each gene and the pathomechanism of the CNS lesions. Understanding of both the clinicopathological characteristics of these CNS lesions and their molecular mechanisms is important for the diagnosis, care of patients, and development of new therapeutic strategies.

Phosphorylation of intact erythrocytes in human muscular dystrophy

International Nuclear Information System (INIS)

Johnson, R.M.; Nigro, M.

1986-01-01

The uptake of exogenous 32 Pi into the membrane proteins of intact erythrocytes was measured in 8 patients with Duchenne muscular dystrophy. No abnormalities were noted after autoradiographic analysis. This contrasts with earlier results obtained when isolated membranes were phosphorylated with gamma-[ 32 P]ATP, and suggests a possible reinterpretation of those experiments

Corneal elastosis within lattice dystrophy lesions.

Science.gov (United States)

Pe'er, J; Fine, B S; Dixon, A; Rothberg, D S

1988-01-01

Corneal buttons of two patients with lattice corneal dystrophy were studied by light and electron microscopy. They showed elastotic degeneration within the amyloid deposits. The amyloid deposits displayed characteristic staining; the elastotic material (elastin) within the deposits stained positive with Verhoeff-van Gieson and Movat pentachrome stains and showed autofluorescence. The characteristic ultrastructural findings of amyloid and elastotic material were also demonstrated. The possibility of the associations of these two materials in the cornea is discussed. Images PMID:3258531

Modulation of Stem Cell Differentiation and Myostatin as an Approach to Counteract Fibrosis in Muscle Dystrophy and Regeneration After Injury. Addendum

Science.gov (United States)

2012-03-01

ged mdx mouse a n ovel therapeutic approach for Duchenne’s muscular dystrophy (DMD) based on the implantation of muscle -derived stem cells (MDSC), and...with limb ischemia. 15. SUBJECT TERMS Myostatin, muscle dystrophy , stem cells, myogenesis, Oct-4; Duchenne ; fibrosis 16. SECURITY CLASSIFICATION...derived stem cells (MDSC) into myogenic, as opposed to lipofibrogenic lineages, is a promising therapeutic strategy for Duchenne muscular dystrophy (DMD

Physical training in boys with Duchenne Muscular Dystrophy: the protocol of the No Use is Disuse study.

NARCIS (Netherlands)

Jansen, M.; Groot, I.J.M. de; Alfen, N. van; Geurts, A.C.H.

2010-01-01

BACKGROUND: "Use it or lose it" is a well known saying which is applicable to boys with Duchenne Muscular Dystrophy (DMD). Besides the direct effects of the muscular dystrophy, the increasing effort to perform activities, the fear of falling and the use of personal aids indirectly impair leg and arm

From proteins to genes: immunoanalysis in the diagnosis of muscular dystrophies

Directory of Open Access Journals (Sweden)

Barresi Rita

2011-06-01

Full Text Available Abstract Muscular dystrophies are a large heterogeneous group of inherited diseases that cause progressive muscle weakness and permanent muscle damage. Very few muscular dystrophies show sufficient specific clinical features to allow a definite diagnosis. Because of the currently limited capacity to screen for numerous genes simultaneously, muscle biopsy is a time and cost-effective test for many of these disorders. Protein analysis interpreted in correlation with the clinical phenotype is a useful way of directing genetic testing in many types of muscular dystrophies. Immunohistochemistry and western blot are complementary techniques used to gather quantitative and qualitative information on the expression of proteins involved in this group of diseases. Immunoanalysis has a major diagnostic application mostly in recessive conditions where the absence of labelling for a particular protein is likely to indicate a defect in that gene. However, abnormalities in protein expression can vary from absence to very subtle reduction. It is good practice to test muscle biopsies with antibodies for several proteins simultaneously and to interpret the results in context. Indeed, there is a degree of direct or functional association between many of these proteins that is reflected by the presence of specific secondary abnormalities that are of value, especially when the diagnosis is not straightforward.

MRI for the demonstration of subclinical muscle involvement in muscular dystrophy

International Nuclear Information System (INIS)

Sookhoo, S.; MacKinnon, I.; Bushby, K.; Chinnery, P.F.; Birchall, D.

2007-01-01

Aim: To compare magnetic resonance imaging (MRI) with clinical examination for the detection of muscle abnormality in patients with muscular dystrophy. Methods: Muscle power in 20 patients with a variety of forms of muscular dystrophy was examined clinically using the Medical Research Council (MRC) grading scale, and patients were subsequently imaged with MRI. MRI and clinical examination for the detection of muscle normality and abnormality were compared using a McNemar chi-squared test to examine differences between the two methods. Results: MRI demonstrated radiological evidence of muscle abnormality more often than clinical examination; 50% of movements assessed as normal on clinical examination were associated with muscle abnormalities on MRI, including a significant proportion where there was severe radiological abnormality, indicating that focally advanced disease may be undetectable clinically. Conclusion: The combination of clinical examination and MRI could improve the accuracy of phenotypic characterization of patients with muscular dystrophy, and this in turn could allow a more focussed molecular analysis through muscle biopsy or genetic investigation. This may also be very helpful in the assessment of the degree of muscle compromise not only in the early phases of the disease but especially during follow-up and can be used in therapeutic trials

Children with central and peripheral neurologic disorders have distinguishable patterns of dysphagia on videofluoroscopic swallow study.

Science.gov (United States)

van den Engel-Hoek, Lenie; Erasmus, Corrie E; van Hulst, Karen C M; Arvedson, Joan C; de Groot, Imelda J M; de Swart, Bert J M

2014-05-01

To determine whether findings on videofluoroscopic swallow studies reveal different patterns of dysphagia between children with central and peripheral neurologic disorders, a retrospective study of 118 videofluoroscopic swallow studies was completed. There were 3 groups: cerebral palsy with only spastic features (n = 53), cerebral palsy with dyskinetic features (n = 34), and neuromuscular disorders (myotonic dystrophy I, n = 5; spinal muscular atrophy I-II, n = 8; Duchenne muscular dystrophy, n = 8; other neuromuscular disorder, n = 10). Interpretation of the videofluoroscopic swallow studies was not blinded. The video fluoroscopic swallow study findings were compared dichotomously between the groups. Children with cerebral palsy demonstrated dysphagia in 1 or all phases of swallowing. In neuromuscular disorder, muscle weakness results in pharyngeal residue after swallow. The underlying swallowing problem in neuromuscular disorder is muscle weakness whereas that in cerebral palsy is more complex, having to do with abnormal control of swallowing. This study serves as a first exploration on specific characteristics of swallowing in different neurologic conditions and will help clinicians anticipate what they might expect.

MBNL142 and MBNL143 gene isoforms, overexpressed in DM1-patient muscle, encode for nuclear proteins interacting with Src family kinases.

Science.gov (United States)

Botta, A; Malena, A; Tibaldi, E; Rocchi, L; Loro, E; Pena, E; Cenci, L; Ambrosi, E; Bellocchi, M C; Pagano, M A; Novelli, G; Rossi, G; Monaco, H L; Gianazza, E; Pantic, B; Romeo, V; Marin, O; Brunati, A M; Vergani, L

2013-08-15

Myotonic dystrophy type-1 (DM1) is the most prevalent form of muscular dystrophy in adults. This disorder is an RNA-dominant disease, caused by expansion of a CTG repeat in the DMPK gene that leads to a misregulation in the alternative splicing of pre-mRNAs. The longer muscleblind-like-1 (MBNL1) transcripts containing exon 5 and the respective protein isoforms (MBNL142-43) were found to be overexpressed in DM1 muscle and localized exclusively in the nuclei. In vitro assays showed that MBNL142-43 bind the Src-homology 3 domain of Src family kinases (SFKs) via their proline-rich motifs, enhancing the SFK activity. Notably, this association was also confirmed in DM1 muscle and myotubes. The recovery, mediated by an siRNA target to Ex5-MBNL142-43, succeeded in reducing the nuclear localization of both Lyn and MBNL142-43 proteins and in decreasing the level of tyrosine phosphorylated proteins. Our results suggest an additional molecular mechanism in the DM1 pathogenesis, based on an altered phosphotyrosine signalling pathway.

Home mechanical ventilation: a Canadian Thoracic Society clinical practice guideline.

Science.gov (United States)

McKim, Douglas A; Road, Jeremy; Avendano, Monica; Abdool, Steve; Cote, Fabien; Duguid, Nigel; Fraser, Janet; Maltais, Fracois; Morrison, Debra L; O'Connell, Colleen; Petrof, Basil J; Rimmer, Karen; Skomro, Robert

2011-01-01

Increasing numbers of patients are surviving episodes of prolonged mechanical ventilation or benefitting from the recent availability of userfriendly noninvasive ventilators. Although many publications pertaining to specific aspects of home mechanical ventilation (HMV) exist, very few comprehensive guidelines that bring together all of the current literature on patients at risk for or using mechanical ventilatory support are available. The Canadian Thoracic Society HMV Guideline Committee has reviewed the available English literature on topics related to HMV in adults, and completed a detailed guideline that will help standardize and improve the assessment and management of individuals requiring noninvasive or invasive HMV. The guideline provides a disease-specific review of illnesses including amyotrophic lateral sclerosis, spinal cord injury, muscular dystrophies, myotonic dystrophy, kyphoscoliosis, post-polio syndrome, central hypoventilation syndrome, obesity hypoventilation syndrome, and chronic obstructive pulmonary disease as well as important common themes such as airway clearance and the process of transition to home. The guidelines have been extensively reviewed by international experts, allied health professionals and target audiences. They will be updated on a regular basis to incorporate any new information.

Dystrophin analysis in carriers of Duchenne and Becker muscular dystrophy

NARCIS (Netherlands)

Hoogerwaard, Edo M.; Ginjaar, Ieke B.; Bakker, Egbert; de Visser, Marianne

2005-01-01

Associations between clinical phenotype (muscle weakness, dilated cardiomyopathy) and dystrophin abnormalities in muscle tissue among definite carriers of Duchenne (DMD) and Becker muscular dystrophy (BMD) were investigated. No associations between dystrophin abnormalities and clinical variables in

TNF-α-Induced microRNAs Control Dystrophin Expression in Becker Muscular Dystrophy.

Science.gov (United States)

Fiorillo, Alyson A; Heier, Christopher R; Novak, James S; Tully, Christopher B; Brown, Kristy J; Uaesoontrachoon, Kitipong; Vila, Maria C; Ngheim, Peter P; Bello, Luca; Kornegay, Joe N; Angelini, Corrado; Partridge, Terence A; Nagaraju, Kanneboyina; Hoffman, Eric P

2015-09-08

The amount and distribution of dystrophin protein in myofibers and muscle is highly variable in Becker muscular dystrophy and in exon-skipping trials for Duchenne muscular dystrophy. Here, we investigate a molecular basis for this variability. In muscle from Becker patients sharing the same exon 45-47 in-frame deletion, dystrophin levels negatively correlate with microRNAs predicted to target dystrophin. Seven microRNAs inhibit dystrophin expression in vitro, and three are validated in vivo (miR-146b/miR-374a/miR-31). microRNAs are expressed in dystrophic myofibers and increase with age and disease severity. In exon-skipping-treated mdx mice, microRNAs are significantly higher in muscles with low dystrophin rescue. TNF-α increases microRNA levels in vitro whereas NFκB inhibition blocks this in vitro and in vivo. Collectively, these data show that microRNAs contribute to variable dystrophin levels in muscular dystrophy. Our findings suggest a model where chronic inflammation in distinct microenvironments induces pathological microRNAs, initiating a self-sustaining feedback loop that exacerbates disease progression. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

TNF-α-Induced microRNAs Control Dystrophin Expression in Becker Muscular Dystrophy

Directory of Open Access Journals (Sweden)

Alyson A. Fiorillo

2015-09-01

Full Text Available The amount and distribution of dystrophin protein in myofibers and muscle is highly variable in Becker muscular dystrophy and in exon-skipping trials for Duchenne muscular dystrophy. Here, we investigate a molecular basis for this variability. In muscle from Becker patients sharing the same exon 45–47 in-frame deletion, dystrophin levels negatively correlate with microRNAs predicted to target dystrophin. Seven microRNAs inhibit dystrophin expression in vitro, and three are validated in vivo (miR-146b/miR-374a/miR-31. microRNAs are expressed in dystrophic myofibers and increase with age and disease severity. In exon-skipping-treated mdx mice, microRNAs are significantly higher in muscles with low dystrophin rescue. TNF-α increases microRNA levels in vitro whereas NFκB inhibition blocks this in vitro and in vivo. Collectively, these data show that microRNAs contribute to variable dystrophin levels in muscular dystrophy. Our findings suggest a model where chronic inflammation in distinct microenvironments induces pathological microRNAs, initiating a self-sustaining feedback loop that exacerbates disease progression.

At the Crossroads of Clinical and Preclinical Research for Muscular Dystrophy-Are We Closer to Effective Treatment for Patients?

Science.gov (United States)

Gawlik, Kinga I

2018-05-16

Among diseases affecting skeletal muscle, muscular dystrophy is one of the most devastating and complex disorders. The term 'muscular dystrophy' refers to a heterogeneous group of genetic diseases associated with a primary muscle defect that leads to progressive muscle wasting and consequent loss of muscle function. Muscular dystrophies are accompanied by numerous clinical complications and abnormalities in other tissues that cause extreme discomfort in everyday life. The fact that muscular dystrophy often takes its toll on babies and small children, and that many patients die at a young age, adds to the cruel character of the disease. Clinicians all over the world are facing the same problem: they have no therapy to offer except for symptom-relieving interventions. Patients, their families, but also clinicians, are in urgent need of an effective cure. Despite advances in genetics, increased understanding of molecular mechanisms underlying muscle disease, despite a sweeping range of successful preclinical strategies and relative progress of their implementation in the clinic, therapy for patients is currently out of reach. Only a greater comprehension of disease mechanisms, new preclinical studies, development of novel technologies, and tight collaboration between scientists and physicians can help improve clinical treatment. Fortunately, inventiveness in research is rapidly extending the limits and setting new standards for treatment design. This review provides a synopsis of muscular dystrophy and considers the steps of preclinical and clinical research that are taking the muscular dystrophy community towards the fundamental goal of combating the traumatic disease.

Clinical and molecular genetic analysis of best vitelliform macular dystrophy.

NARCIS (Netherlands)

Boon, C.J.F.; Theelen, T.; Hoefsloot, L.H.; Schooneveld, M.J. van; Keunen, J.E.E.; Cremers, F.P.M.; Klevering, B.J.; Hoyng, C.B.

2009-01-01

PURPOSE: To describe the phenotype of Best vitelliform macular dystrophy (BVMD) and to evaluate genotype-phenotype and histopathologic correlations. METHODS: Retrospective analysis of patients with BVMD who underwent an extensive ophthalmic examination, including best-corrected Snellen visual

CLINICAL AND MOLECULAR GENETIC ANALYSIS OF BEST VITELLIFORM MACULAR DYSTROPHY

NARCIS (Netherlands)

Boon, Camiel J. F.; Theelen, Thomas; Hoefsloot, Elisabeth H.; van Schooneveld, Mary J.; Keunen, Jan E. E.; Cremers, Frans P. M.; Klevering, B. Jeroen; Hoyng, Carel B.

2009-01-01

Purpose: To describe the phenotype of Best vitelliform macular dystrophy (BVMD) and to evaluate genotype-phenotype and histopathologic correlations. Methods: Retrospective analysis of patients with BVMD who underwent an extensive ophthalmic examination, including best-corrected Snellen visual

Dysphagia in Duchenne Muscular Dystrophy Assessed by Validated Questionnaire

Science.gov (United States)

Archer, Sally K.; Garrod, Rachel; Hart, Nicholas; Miller, Simon

2013-01-01

Background: Duchenne muscular dystrophy (DMD) leads to progressive muscular weakness and death, most typically from respiratory complications. Dysphagia is common in DMD; however, the most appropriate swallowing assessments have not been universally agreed and the symptoms of dysphagia remain under-reported. Aims: To investigate symptoms of…

Why short stature is beneficial in Duchenne muscular dystrophy.

Science.gov (United States)

Bodor, Marko; McDonald, Craig M

2013-09-01

Duchenne muscular dystrophy (DMD) is caused by a genetic defect resulting in absent dystrophin, yet children are able to walk when small and young but lose this ability as they grow. The mdx mouse has absent dystrophin yet does not exhibit significant disability. Allometric modeling of linearly increasing load per muscle fiber and stress on the sarcolemma with growth and exponential decline associated with loss of muscle fibers correlated with case studies and animal models of DMD. Smaller species or breeds are predictably less affected than large as follows: mdx mice muscular dystrophy (GRMD) dogs < large GRMD dogs < humans. Case reports of combined growth hormone and dystrophin deficiency show a relatively benign course of disease. Future therapeutic trials in DMD might include specific growth inhibitors in combination with standard of care treatments to delay the clinical onset and reduce the severity of disease and disability. Copyright © 2013 Wiley Periodicals, Inc.

Challenges to oligonucleotides-based therapeutics for Duchenne muscular dystrophy

Directory of Open Access Journals (Sweden)

Goyenvalle Aurélie

2011-02-01

Full Text Available Abstract Antisense oligonucleotides are short nucleic acids designed to bind to specific messenger RNAs in order to modulate splicing patterns or inhibit protein translation. As such, they represent promising therapeutic tools for many disorders and have been actively developed for more than 20 years as a form of molecular medicine. Although significant progress has been made in developing these agents as drugs, they are yet not recognized as effective therapeutics and several hurdles remain to be overcome. Within the last few years, however, the prospect of successful oligonucleotides-based therapies has moved a step closer, in particular for Duchenne muscular dystrophy. Clinical trials have recently been conducted for this myopathy, where exon skipping is being used to achieve therapeutic outcomes. In this review, the recent developments and clinical trials using antisense oligonucleotides for Duchenne muscular dystrophy are discussed, with emphasis on the challenges ahead for this type of therapy, especially with regards to delivery and regulatory issues.

Clinical-Diagnostic Features of Duchenne Muscular Dystrophy in Children

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Umida T. Omonova

2013-12-01

Full Text Available Duchenne Muscular Dystrophy (DMD is a severe, progressive disease that affects about 1 out of every 5,000 male infants; this is the most destructive of all muscular dystrophies, which worsens rapidly. In this study, we performed a clinical analysis of 37 children with DMD. They ranged in age from 3 to 15 years, mean age being 7.8±0.48 years. The mean age at onset was 4.3±0.36 years and ranged from birth to 8 years. The biochemical examination included the determination of the serum levels of the following enzymes, AST, ALT, CPK-MM, and LDH. A genealogical analysis was conducted among 240 first-degree relatives of children with DMD. Electroneuromyography examination included registration of the biopotentials of the hand and foot muscles, measurement of the muscle response (M-wave and the late-evoked responses. The clinical-diagnostic features of DMD in children were characterized.

NMNAT1 variants cause cone and cone-rod dystrophy.

Science.gov (United States)

Nash, Benjamin M; Symes, Richard; Goel, Himanshu; Dinger, Marcel E; Bennetts, Bruce; Grigg, John R; Jamieson, Robyn V

2018-03-01

Cone and cone-rod dystrophies (CD and CRD, respectively) are degenerative retinal diseases that predominantly affect the cone photoreceptors. The underlying disease gene is not known in approximately 75% of autosomal recessive cases. Variants in NMNAT1 cause a severe, early-onset retinal dystrophy called Leber congenital amaurosis (LCA). We report two patients where clinical phenotyping indicated diagnoses of CD and CRD, respectively. NMNAT1 variants were identified, with Case 1 showing an extremely rare homozygous variant c.[271G > A] p.(Glu91Lys) and Case 2 compound heterozygous variants c.[53 A > G];[769G > A] p.(Asn18Ser);(Glu257Lys). The detailed variant analysis, in combination with the observation of an associated macular atrophy phenotype, indicated that these variants were disease-causing. This report demonstrates that the variants in NMNAT1 may cause CD or CRD associated with macular atrophy. Genetic investigations of the patients with CD or CRD should include NMNAT1 in the genes examined.

Deletion of exon 26 of the dystrophin gene is associated with a mild Becker muscular dystrophy phenotype

DEFF Research Database (Denmark)

Witting, Nanna; Duno, Morten; Vissing, John

2011-01-01

With the possible introduction of exon skipping therapy in Duchenne muscular dystrophy, it has become increasingly important to know the role of each exon of the dystrophin gene to protein expression, and thus the phenotype. In this report, we present two related men with an unusually mild BMD...... calf hypertrophy was noted. Creatine kinase was normal or raised maximally to 500 U/l. The muscle biopsy was myopathic with increased fiber size variation and many internal nuclei, but no dystrophy. No comorbidity was found. In both cases, western blot showed a reduced dystrophin band. Genetic...... skipping therapy for Duchenne muscular dystrophy. This report also shows that BMD may present with a normal CK....

[Two cases of Duchenne muscular dystrophy over 40 years after onset].

Science.gov (United States)

Ishizaki, Masatoshi; Ueyama, Hidetsugu; Masuda, Teruaki; Nishida, Yasuto; Imamura, Shigehiro; Ando, Yukio

2013-01-01

We report two 45 year old men with Duchenne muscular dystrophy. Case 1 showed a deleted exon 50 of the dystrophin gene by MLPA analysis, and Case 2 showed deleted exons 46-52. Both patients presented with severe weakness of the skeletal muscles and respiratory dysfunction, while cardiac involvement was mild and cognitive function was almost normal. The patients are able to shop at a mall, participate in activities, and attend hobbies, although they are bedridden with artificial respiration through tracheotomy. With the progress of the respiratory care and cardiac protective therapy, the prognosis of Duchenne muscular dystrophy has improved remarkably. At present, it is possible to survive over 40 years with maintenance of quality of life, if cardiac damage is not severe.

Dystrophin Immunity in Duchenne’s Muscular Dystrophy

OpenAIRE

Mendell, Jerry R.; Campbell, Katherine; Rodino-Klapac, Louise; Sahenk, Zarife; Shilling, Chris; Lewis, Sarah; Bowles, Dawn; Gray, Steven; Li, Chengwen; Galloway, Gloria; Malik, Vinod; Coley, Brian; Clark, K. Reed; Li, Juan; Xiao, Xiao

2010-01-01

We report on delivery of a functional dystrophin transgene to skeletal muscle in six patients with Duchenne’s muscular dystrophy. Dystrophin-specific T cells were detected after treatment, providing evidence of transgene expression even when the functional protein was not visualized in skeletal muscle. Circulating dystrophin-specific T cells were unexpectedly detected in two patients before vector treatment. Revertant dystrophin fibers, which expressed functional, truncated dystrophin from th...

High-intensity interval training in facioscapulohumeral muscular dystrophy type 1

DEFF Research Database (Denmark)

Andersen, Grete; Heje, Karen; Buch, Astrid Emile

2017-01-01

of muscle damage in facioscapulohumeral muscular dystrophy type 1 (FSHD1). We aimed to determine whether HIT is safe and effective in FSHD1 in a randomized, controlled parallel study. Untrained adults with genetically verified FSHD1 (n = 13) able to perform cycle-ergometer exercise were randomized to 8......, workload, 6-min walk distance, 5-time sit-to-stand time, muscle strength, and daily activity levels were measured. Pain, fatigue, and plasma-CK were monitored. Twelve patients completed the randomized part of the study. Plasma-CK levels and pain scores were unaffected by HIT. Supervised HIT improved...... counterintuitive to perform HIT in muscular dystrophies, but this RCT shows that regular HIT is safe, efficacious, and well liked by moderately affected patients with FSHD1, which suggests that HIT is a feasible method for rehabilitating patients with FSHD1....

Reflex sympathetic dystrophy/complex regional pain syndrome, type 1

African Journals Online (AJOL)

Enrique

with MRI every 3 months and the bone marrow oedema disappeared after 6 months. Introduction ... SA JOURNAL OF RADIOLOGY • August 2004. Reflex sympathetic dystrophy/complex regional pain syndrome, type 1 ... may be either trauma of external origin or iatrogenic, post surgery. In some patients particularly children ...

Occupational Potential in a Population with Duchenne Muscular Dystrophy.

Science.gov (United States)

Schkade, Janette K.; And Others

1987-01-01

Twenty-five males with Duchenne muscular dystrophy were tested to assess their potential for occupational activity. Tests measured possible sensory deficits, strength, endurance, and fatigue in response to sustained fine motor activity. Results indicate that, within limitations, persons with this diagnosis can engage in activity leading to skill…

Treatment of Reflex sympathetic dystrophy with Bee venom -Using Digital Infrared Thermographic Imaging-

Directory of Open Access Journals (Sweden)

Myung-jang Lim

2006-12-01

Full Text Available Objectives : The purpose of this case is to report the patient with Reflex sympathetic dystrophy, who is improved by Bee venom. Method : We treated the patient with Bee venom who was suffering from Reflex sympathetic dystrophy, using Digital Infrared Thermographic Imaging and Verbal Numerical Rating Scale(VNRS to evaluate the therapeutic effects. We compared the temperature of the patient body before and after treatment. Result and Conclusion : We found that Bee venom had excellent outcome to relieve pain, atrophy and ankle joint ROM, and that Bee venom also had clinical effect on hypothermia on the Digital Infrared Thermographic Imaging.

Decreased Nocturnal Movements in Patients with Facioscapulohumeral Muscular Dystrophy

Science.gov (United States)

Marca, Giacomo Della; Frusciante, Roberto; Dittoni, Serena; Vollono, Catello; Losurdo, Anna; Testani, Elisa; Scarano, Emanuele; Colicchio, Salvatore; Iannaccone, Elisabetta; Tonali, Pietro A.; Ricci, Enzo

2010-01-01

Study Objectives: Reduced mobility during sleep characterizes a variety of movement disorders and neuromuscular diseases. Facioscapulohumeral muscular dystrophy (FSHD) is the third most common form of muscular dystrophy in the general population, and people with FSHD have poor sleep quality. The aims of the present study were to evaluate nocturnal motor activity in patients with FSHD by means of videopolysomnography and to verify whether activity was associated with modifications in sleep structure. Methods: We enrolled 32 adult patients affected by genetically confirmed FSHD (18 women and 14 men, mean age 45.1 ± 13.4 years) and 32 matched control subjects, (18 women and 14 men, mean age 45.5 ± 11.4 years). Major body movements (MBM) were scored in videopolygraphic recordings in accordance with established criteria. An MBM index was calculated (number of MBM per hour of sleep). Results: The FSHD group showed a decrease in the MBM index (FSHD: 1.2 ± 1.1; control subjects: 2.3 ± 1.2, analysis of variance F = 13.672; p = 0.008). The sleep pattern of patients with FSHD, as compared with that of controls, was characterized by longer sleep latencies, shorter sleep durations, an increased percentage of wake during sleep, and a decreased percentage of rapid eye movement sleep. In the patient group, the MBM index was inversely correlated with severity of disease (Spearman test: r30 = −0.387; p Marca GD; Frusciante R; Dittoni S; Vollono C; Losurdo A; Testani E; Scarano E; Colicchio S; Iannaccone E; Tonali PA; Ricci E. Decreased nocturnal movements in patients with facioscapulohumeral muscular dystrophy. J Clin Sleep Med 2010;6(3):276-280. PMID:20572422

Standard Operating Procedures (SOPs) for Evaluating the Heart in Preclinical Studies of Duchenne Muscular Dystrophy.

Science.gov (United States)

Duan, Dongsheng; Rafael-Fortney, Jill A; Blain, Alison; Kass, David A; McNally, Elizabeth M; Metzger, Joseph M; Spurney, Christopher F; Kinnett, Kathi

2016-02-01

A recent working group meeting focused on contemporary cardiac issues in Duchenne muscular dystrophy (DMD) was hosted by the National Heart, Lung, and Blood Institute in collaboration with the Parent Project Muscular Dystrophy. An outcome of this meeting was to provide freely available detailed protocols for preclinical animal studies. The goal of these protocols is to improve the quality and reproducibility of cardiac preclinical studies aimed at developing new therapeutics for the prevention and treatment of DMD cardiomyopathy.

Dysferlin, annexin A1, and mitsugumin 53 are upregulated in muscular dystrophy and localize to longitudinal tubules of the T-system with stretch.

Science.gov (United States)

Waddell, Leigh B; Lemckert, Frances A; Zheng, Xi F; Tran, Jenny; Evesson, Frances J; Hawkes, Joanne M; Lek, Angela; Street, Neil E; Lin, Peihui; Clarke, Nigel F; Landstrom, Andrew P; Ackerman, Michael J; Weisleder, Noah; Ma, Jianjie; North, Kathryn N; Cooper, Sandra T

2011-04-01

Mutations in dysferlin cause an inherited muscular dystrophy because of defective membrane repair. Three interacting partners of dysferlin are also implicated in membrane resealing: caveolin-3 (in limb girdle muscular dystrophy type 1C), annexin A1, and the newly identified protein mitsugumin 53 (MG53). Mitsugumin 53 accumulates at sites of membrane damage, and MG53-knockout mice display a progressive muscular dystrophy. This study explored the expression and localization of MG53 in human skeletal muscle, how membrane repair proteins are modulated in various forms of muscular dystrophy, and whether MG53 is a primary cause of human muscle disease. Mitsugumin 53 showed variable sarcolemmal and/or cytoplasmic immunolabeling in control human muscle and elevated levels in dystrophic patients. No pathogenic MG53 mutations were identified in 50 muscular dystrophy patients, suggesting that MG53 is unlikely to be a common cause of muscular dystrophy in Australia. Western blot analysis confirmed upregulation of MG53, as well as of dysferlin, annexin A1, and caveolin-3 to different degrees, in different muscular dystrophies. Importantly, MG53, annexin A1, and dysferlin localize to the t-tubule network and show enriched labeling at longitudinal tubules of the t-system in overstretch. Our results suggest that longitudinal tubules of the t-system may represent sites of physiological membrane damage targeted by this membrane repair complex.

What Can DuchenneConnect Teach Us About Treating Duchenne Muscular Dystrophy?

Science.gov (United States)

Wang, Richard T; Nelson, Stanley F

2015-01-01

Purpose of Review This review aims to describe the benefits and limitations of using the DuchenneConnect patient registry to provide information particularly in regard to active treatment choices in Duchenne muscular dystrophy and their impact on disease progression. Recent findings Clinical trials and natural history studies are difficult for rare diseases like Duchenne muscular dystrophy. Using an online patient self-report survey model, DuchenneConnect provides relevant data that are difficult to gather in other ways. Validation of the overall dataset is supported by comparable mutational spectrum relative to other cohorts and demonstrated beneficial effect of corticosteroid use in prolonging ambulation. These types of analyses are provocative and allow multivariate analyses across the breadth of patient and physician medication and supplement practices. Because the data is self-reported and online, the barrier to participation is low and great potential exists for novel directions of further research in a highly participatory forum. Summary Patient registries for Duchenne and Becker muscular dystrophy are powerful tools for monitoring patient outcomes, comparing treatments options, and relating information between patients, researchers and clinicians. DuchenneConnect is an online patient self-report registry for individuals with DBMD that facilitates aggregation of treatment modalities, outcomes and genotype data and has played a vital role in furthering DBMD research, particularly in the US, in a highly participatory and low cost manner. PMID:26356412

What can Duchenne Connect teach us about treating Duchenne muscular dystrophy?

Science.gov (United States)

Wang, Richard T; Nelson, Stanley F

2015-10-01

This review aims to describe the benefits and limitations of using the Duchenne Connect patient registry to provide information particularly in regard to active treatment choices in Duchenne muscular dystrophy and their impact on disease progression. Clinical trials and natural history studies are difficult for rare diseases like Duchenne muscular dystrophy. Using an online patient self-report survey model, Duchenne Connect provides relevant data that are difficult to gather in other ways. Validation of the overall dataset is supported by comparable mutational spectrum relative to other cohorts and demonstrated beneficial effect of corticosteroid use in prolonging ambulation. These types of analyses are provocative and allow multivariate analyses across the breadth of patient and physician medication and supplement practices. Because the data are self-reported and online, the barrier to participation is low and great potential exists for novel directions of further research in a highly participatory forum. Patient registries for Duchenne and Becker muscular dystrophy (DBMD) are powerful tools for monitoring patient outcomes, comparing treatment options, and relating information between patients, researchers, and clinicians. Duchenne Connect is an online patient self-report registry for individuals with DBMD that facilitates aggregation of treatment modalities, outcomes, and genotype data and has played a vital role in furthering DBMD research, particularly in the USA, in a highly participatory and low-cost manner.

Muscle MRI findings in patients with limb girdle muscular dystrophy with calpain 3 deficiency (LGMD2A) and early contractures.

Science.gov (United States)

Mercuri, Eugenio; Bushby, Kate; Ricci, Enzo; Birchall, Daniel; Pane, Marika; Kinali, Maria; Allsop, Joanna; Nigro, Vincenzo; Sáenz, Amets; Nascimbeni, Annachiara; Fulizio, Luigi; Angelini, Corrado; Muntoni, Francesco

2005-02-01

Limb girdle muscular dystrophy 2A is a common variant secondary to mutations in the calpain 3 gene. A proportion of patients has early and severe contractures, which can cause diagnostic difficulties with other conditions. We report clinical and muscle magnetic resonance imaging findings in seven limb girdle muscular dystrophy 2A patients (four sporadic and three familial) who had prominent and early contractures. All patients showed a striking involvement of the posterior thigh muscles. The involvement of the other thigh muscles was variable and was related to clinical severity. Young patients with minimal functional motor impairment showed a predominant involvement of the adductors and semimembranosus muscles while patients with restricted ambulation had a more diffuse involvement of the posterolateral muscles of the thigh and of the vastus intermedius with relative sparing of the vastus lateralis, sartorius and gracilis. At calf level all patients showed involvement of the soleus muscle and of the medial head of the gastrocnemius with relative sparing of the lateral head. MRI findings were correlated to those found in two patients with the phenotype of limb girdle muscular dystrophy 2A without early contractures and the pattern observed was quite similar. However, the pattern observed in limb girdle muscular dystrophy 2A is different from that reported in other muscle diseases such as Emery-Dreifuss muscular dystrophy and Bethlem myopathy which have a significant clinical overlap with limb girdle muscular dystrophy 2A once early contractures are present. Our results suggest that muscle MRI may help in recognising patients with limb girdle muscular dystrophy 2A even when the clinical presentation overlaps with other conditions, and may therefore, be used as an additional investigation to target the appropriate biochemical and genetic tests.

Successful bone marrow transplantation in a patient with Diamond-Blackfan anemia with co-existing Duchenne muscular dystrophy: a case report

Directory of Open Access Journals (Sweden)

Kaur Jasmeet

2011-06-01

Full Text Available Abstract Introduction Diamond-Blackfan anemia and Duchenne muscular dystrophy are two rare congenital anomalies. Both anomalies occurring in the same child is extremely rare. Allogeneic hematopoietic stem cell transplantation is a well-established therapy for Diamond-Blackfan anemia. However, in patients with Duchenne muscular dystrophy, stem cell therapy still remains experimental. Case presentation We report the case of a nine-year-old boy of north Indian descent with Diamond-Blackfan anemia and Duchenne muscular dystrophy who underwent successful allogeneic hematopoietic stem cell transplantation. He is transfusion-independent, and his Duchenne muscular dystrophy has shown no clinical deterioration over the past 45 months. His creatine phosphokinase levels have significantly decreased to 300 U/L from 14,000 U/L pre-transplant. The patient is 100% donor chimera in the hematopoietic system, and his muscle tissue has shown 8% to 10.4% cells of donor origin. Conclusion Our patient's Diamond-Blackfan anemia was cured by allogeneic hematopoietic stem cell transplantation. The interesting clinical observation of a possible benefit in Duchenne muscular dystrophy cannot be ruled out. However, further clinical follow-up with serial muscle biopsies and molecular studies are needed to establish this finding.

Impact of three genetic musculoskeletal diseases: a comparative synthesis of achondroplasia, Duchenne muscular dystrophy and osteogenesis imperfecta.

Science.gov (United States)

Dogba, Maman Joyce; Rauch, Frank; Douglas, Erin; Bedos, Christophe

2014-10-25

Achondroplasia, Duchenne muscular dystrophy, and osteogenesis imperfecta are among the most frequent rare genetic disorders affecting the musculoskeletal system in children. Rare genetic disorders are severely disabling and can have substantial impacts on families, children, and on healthcare systems. This literature review aims to classify, summarize and compare these non-medical impacts of achondroplasia, Duchenne muscular dystrophy and osteogenesis imperfecta.

Disability and Survival in Duchenne Muscular Dystrophy

OpenAIRE

Kohler, M; Clarenbach, C F; Bahler, C; Brack, T; Russi, E W; Bloch, K E

2009-01-01

BACKGROUND: Duchenne muscular dystrophy (DMD) leads to progressive impairment of muscle function, respiratory failure and premature death. Longitudinal data on the course of physical disability and respiratory function are sparse. OBJECTIVES: To prospectively assess physical impairment and disability, respiratory function and survival in DMD patients over several years in order to describe the course of the disease with current care. METHODS: In 43 patients with DMD, aged 5-35 years, yearly a...

Translating golden retriever muscular dystrophy microarray findings to novel biomarkers for cardiac/skeletal muscle function in Duchenne muscular dystrophy.

Science.gov (United States)

Galindo, Cristi L; Soslow, Jonathan H; Brinkmeyer-Langford, Candice L; Gupte, Manisha; Smith, Holly M; Sengsayadeth, Seng; Sawyer, Douglas B; Benson, D Woodrow; Kornegay, Joe N; Markham, Larry W

2016-04-01

In Duchenne muscular dystrophy (DMD), abnormal cardiac function is typically preceded by a decade of skeletal muscle disease. Molecular reasons for differences in onset and progression of these muscle groups are unknown. Human biomarkers are lacking. We analyzed cardiac and skeletal muscle microarrays from normal and golden retriever muscular dystrophy (GRMD) dogs (ages 6, 12, or 47+ mo) to gain insight into muscle dysfunction and to identify putative DMD biomarkers. These biomarkers were then measured using human DMD blood samples. We identified GRMD candidate genes that might contribute to the disparity between cardiac and skeletal muscle disease, focusing on brain-derived neurotropic factor (BDNF) and osteopontin (OPN/SPP1, hereafter indicated as SPP1). BDNF was elevated in cardiac muscle of younger GRMD but was unaltered in skeletal muscle, while SPP1 was increased only in GRMD skeletal muscle. In human DMD, circulating levels of BDNF were inversely correlated with ventricular function and fibrosis, while SPP1 levels correlated with skeletal muscle function. These results highlight gene expression patterns that could account for differences in cardiac and skeletal disease in GRMD. Most notably, animal model-derived data were translated to DMD and support use of BDNF and SPP1 as biomarkers for cardiac and skeletal muscle involvement, respectively.

Cardiac involvement in carriers of Duchenne and Becker muscular dystrophy

NARCIS (Netherlands)

Hoogerwaard, EM; van der Wouw, PA; Wilde, AAM; Bakker, E; Ippel, PF; Oosterwijk, JC; Majoor-Krakauer, DF; van Essen, AJ; Leschot, NJ; de Visser, Marianne

A cross-sectional study in a cohort of DNA proven carriers of Duchenne (DMD) and Becker (BMD) muscular dystrophy was undertaken with the following objectives: (1) to estimate the frequency of electrocardiographic (ECG) and echocardiographic abnormalities; (2) to establish the proportion of carriers

Computed tomographic findings in manifesting carriers of Duchenne muscular dystrophy

NARCIS (Netherlands)

de Visser, M.; Verbeeten, B.

1985-01-01

Clinical and computed tomographic (CT) findings in 3 manifesting carriers of Duchenne muscular dystrophy are reported. CT proved to be an important adjunct to the clinical examination: in all our 3 cases a decrease in density was found in various non-paretic muscles

Quantitative assessment of calf circumference in Duchenne muscular dystrophy patients

NARCIS (Netherlands)

Beenakker, EAC; de Vries, Joeke; Fock, JM; van Tol, M; Brouwer, OF; Maurits, NM; van der Hoeven, JH

2002-01-01

Duchenne muscular dystrophy is clinically characterised by progressive muscle weakness and a gradual increase in the size of some affected muscles, especially calf muscles. The extent of calf enlargement is usually determined by subjective visual assessment. The purpose of this study was to

Atypical vitelliform macular dystrophy misdiagnosed as chronic central serous chorioretinopathy: case reports

Directory of Open Access Journals (Sweden)

Lee Young

2012-07-01

Full Text Available Abstract Background To report two cases of atypical vitelliform macular dystrophy misdiagnosed as chronic central serous chorioretinopathy. Case presentation Two patients with incidentally discovered abnormalities of the retina without specific symptoms were referred to our hospital for consultation. Bilateral macula atrophic lesions were observed and optical coherence tomography revealed serous retinal detachment in the macula. Fluorescein angiography showed multiple leakages around the central hypofluorescent area and indocyanine green angiography showed partially dilated choroidal vessels. Fundus autofluorescence (FAF showed a decreasing pattern of autofluorescence in the subretinal fluid area, and increasing autofluorescence at the border of the serous retinal detachment. Both patients were diagnosed with chronic central serous chorioretinopathy. Photodynamic therapy and intravitreal bevacizumab injection were administered for engorged choroidal vessels during follow-up, but neither patient showed improvement in symptoms or ophthalmologic findings. Based on re-evaluation by fundus photography, optical coherence tomography, fluorescein angiography, and comparison of the results of FAF with the first visit, vitelliform macular dystrophy was suspected and a definite diagnosis was made by electrooculography and genetic testing. Conclusion In patients with continuous serous retinal detachment without response to photodynamic therapy or intravitreal bevacizumab injection, careful fundus exam and FAF can be used to diagnose atypical vitelliform macular dystrophy.

An Overview of Recent Therapeutics Advances for Duchenne Muscular Dystrophy.

Science.gov (United States)

Mah, Jean K

2018-01-01

Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. Mutations of the DMD gene destabilize the dystrophin associated glycoprotein complex in the sarcolemma. Ongoing mechanical stress leads to unregulated influx of calcium ions into the sarcoplasm, with activation of proteases, release of proinflammatory cytokines, and mitochondrial dysfunction. Cumulative damage and reparative failure leads to progressive muscle necrosis, fibrosis, and fatty replacement. Although there is presently no cure for DMD, scientific advances have led to many potential disease-modifying treatments, including dystrophin replacement therapies, upregulation of compensatory proteins, anti-inflammatory agents, and other cellular targets. Recently approved therapies include ataluren for stop codon read-through and eteplirsen for exon 51 skipping of eligible individuals. The purpose of this chapter is to summarize the clinical features of DMD, to describe current outcome measures used in clinical studies, and to highlight new emerging therapies for affected individuals.

Risk Factors for First Fractures Among Males With Duchenne or Becker Muscular Dystrophy.

Science.gov (United States)

James, Katherine A; Cunniff, Christopher; Apkon, Susan D; Mathews, Katherine; Lu, Zhenqiang; Holtzer, Caleb; Pandya, Shree; Ciafaloni, Emma; Miller, Lisa

2015-09-01

Fractures are a significant concern for individuals with Duchenne/Becker muscular dystrophy with 21% to 44% of males experiencing a fracture. Factors that increase or decrease the risk for fracture have been suggested in past research, although statistical risk has not been determined. In this retrospective cohort study, we used the Muscular Dystrophy Surveillance, Tracking and Research Network cohort, a large, population-based sample to identify risk factors associated with first fractures in patients with Duchenne or Becker muscular dystrophy. Our study cohort included males with Duchenne or Becker muscular dystrophy born between 1982 and 2006 who resided in Arizona, Colorado, Georgia, Iowa, and Western New York, retrospectively identified and followed through 2010. We utilized a multivariate Cox proportional hazard model to determine hazard ratios for relevant factors associated with first fracture risk including race/ethnicity, surveillance site, ambulation status, calcium/vitamin D use and duration, bisphosphonate use and duration, and corticosteroid use and duration. Of 747 cases, 249 had at least 1 fracture (33.3%). Full-time wheelchair use increased the risk of first fracture by 75% for every 3 months of use (hazard ratio=1.75, 95% confidence interval, 1.14, 2.68), but corticosteroid use, bisphosphonate use, and calcium/vitamin D use did not significantly affect risk in the final adjusted model. In this cohort, first fractures were common and full-time wheelchair use, but not corticosteroid use, was identified as a risk factor. The impact of prevention measures should be more thoroughly assessed. Fractures are a significant concern for individuals with dystrophinopathies, but the contribution of various risk factors has not been consistently demonstrated.

Epigenetic Regulators Modulate Muscle Damage in Duchenne Muscular Dystrophy Model.

Science.gov (United States)

Bajanca, Fernanda; Vandel, Laurence

2017-12-21

Histone acetyl transferases (HATs) and histone deacetylases (HDAC) control transcription during myogenesis. HDACs promote chromatin condensation, inhibiting gene transcription in muscle progenitor cells until myoblast differentiation is triggered and HDACs are released. HATs, namely CBP/p300, activate myogenic regulatory and elongation factors promoting myogenesis. HDAC inhibitors are known to improve regeneration in dystrophic muscles through follistatin upregulation. However, the potential of directly modulating HATs remains unexplored. We tested this possibility in a well-known zebrafish model of Duchenne muscular dystrophy. Interestingly, CBP/p300 transcripts were found downregulated in the absence of Dystrophin. While investigating CBP rescuing potential we observed that dystrophin-null embryos overexpressing CBP actually never show significant muscle damage, even before a first regeneration cycle could occur. We found that the pan-HDAC inhibitor trichostatin A (TSA) also prevents early muscle damage, however the single HAT CBP is as efficient even in low doses. The HAT domain of CBP is required for its full rescuing ability. Importantly, both CBP and TSA prevent early muscle damage without restoring endogenous CBP/p300 neither increasing follistatin transcripts. This suggests a new mechanism of action of epigenetic regulators protecting dystrophin-null muscle fibres from detaching, independent from the known improvement of regeneration upon damage of HDACs inhibitors. This study builds supporting evidence that epigenetic modulators may play a role in determining the severity of muscle dystrophy, controlling the ability to resist muscle damage. Determining the mode of action leading to muscle protection can potentially lead to new treatment options for muscular dystrophies in the future.

Merosin/laminin-2 and muscular dystrophy

DEFF Research Database (Denmark)

Wewer, U M; Engvall, E

1996-01-01

structural organization of domains, some of which have been assigned biological activities, including self-assembly and interactions with other proteins. The particular importance of laminins for the formation and stability of cell adhesion complexes is highlighted in severe inherited diseases of muscle...... and skin. Merosin is the collective name for laminins that share a common subunit, the laminin alpha 2 chain. Merosin-deficient congenital muscular dystrophy (CMD) is caused by mutations in the laminin alpha 2 chain gene. The skin disease Herlitz junctional epidermolysis bullosa is caused by mutations...

Co-incidence of Turner syndrome and Duchenne muscular dystrophy - an important problem for the clinician.

Science.gov (United States)

Kaczorowska, Ewa; Zimowski, Janusz; Cichoń-Kotek, Monika; Mrozińska, Agnieszka; Purzycka, Joanna; Wierzba, Jolanta; Limon, Janusz; Lipska-Ziętkiewicz, Beata S

Turner syndrome is a relatively common chromosomal disorder which affects about one in 2000 live born females. Duchenne muscular dystrophy is an X-linked recessive disorder affecting 1:3600 live born males. Considering the above, the coexistence of these two diseases may occur only anecdotally. Here, we report a 4 ½ year-old female with classical 45,X Turner syndrome who also had Duchenne muscular dystrophy caused by a point mutation in the dystrophin gene (c.9055delG). The patient showed the typical phenotype of Turner syndrome including distinctive dysmorphic features (short neck, low posterior hairline, wide position of nipples), aortic coarctation and feet lymphedema. Besides, she presented with an unusually early beginning of muscular dystrophy symptoms with infantile-onset motor developmental delay, intellectual disability and early calf muscular hypertrophy. The coexistence of an X-linked recessive disorder should be considered in women affected by Turner syndrome presenting with additional atypical clinical features.

Usefulness of sugammadex in a patient with Becker muscular dystrophy and dilated cardiomyopathy.

Science.gov (United States)

Shimauchi, Tsukasa; Yamaura, Ken; Sugibe, Sayaka; Hoka, Sumio

2014-09-01

A 54-year-old patient with Becker muscular dystrophy and dilated cardiomyopathy underwent laparoscopic cholecystectomy under total intravenous anesthesia. Muscle relaxation was induced by rocuronium (0.4 mg/kg body weight) under train-of-four (TOF) ratio monitoring. The TOF ratio was 0 at intubation, and 0.2 at the end of surgery. Residual muscle relaxant activity was successfully reversed by sugammadex (2 mg/kg body weight) without any hemodynamic adverse effects (TOF ratio 1.0 at extubation). The clinical and hemodynamic findings suggest that sugammadex can be safely used in patients with Becker muscular dystrophy and dilated cardiomyopathy. Copyright © 2014. Published by Elsevier B.V.

Antisense mediated exon skipping therapy for duchenne muscular dystrophy (DMD)

DEFF Research Database (Denmark)

Brolin, Camilla; Shiraishi, Takehiko

2011-01-01

Duchenne Muscular Dystrophy (DMD) is a lethal disease caused by mutations in the dystrophin gene (DMD) that result in the absence of essential muscle protein dystrophin. Among many different approaches for DMD treatment, exon skipping, mediated by antisense oligonucleotides, is one of the most...

Three-dimensional brain-surface MR images of brain anomalies in Fukuyama congenital muscular dystrophy and its differentiation from Duchenne muscular dystrophy with severe mental retardation

Energy Technology Data Exchange (ETDEWEB)

Toda, Tatsushi; Watanabe, Toshiaki; Shimizu, Teruo; Iwata, Makoto; Kanazawa, Ichiro (Tokyo Univ. (Japan). Faculty of Medicine); Matsumura, Kiichiro

1993-12-01

Fukuyama congenital muscular dystrophy (FCMD) is the second most common form of muscular dystrophy in Japan and is peculiarly associated with brain anomalies such as micropolygyria. Since these anomalies are preferentially observed on the brain surface, it is difficult to identify them by either X-ray CT or conventional MRI. In addition, FCMD has an atypical (mild) form in which the patients are capable of walking. In such cases, clinical differential diagnosis from Duchenne muscular dystrophy with severe mental retardation (DMD-MR) is not necessarily easy. We analyzed the brain-surface structures of 4 typical FCMD cases. 1 atypical FCMD case, 4 DMD-MR cases, and 1 undiagnosed case using a method of 3-dimensional (3-D) brain-surface MR imaging; we then compared the results with dystrophin immuno-stainings of the biopsied skeletal muscles. In both typical and atypical FCMD cases, micropolygyria could be clearly demonstrated, with individual variations. The 3-D images were verified by neuropathology. Of the 4 DMD-MR cases, 3 cases showed no gyral abnormality. However, in 1 DMD-MR case the diagnosis was corrected to atypical FCMD because of micropolygyria found on 3-D MRI. The one undiangosed case was diagnosed as DMD-MR on the basis of 3-D MRI. There was a good correspondence between the results of the 3-D imaging and the dystrophin test. Recently, some FCMD cases with a complete deficiency of dystrophin have been reported. Therefore, the detection of brain anomalies is important for the precise diagnosis of FCMD; the present method is considered effective for this purpose. (author).

Three-dimensional brain-surface MR images of brain anomalies in Fukuyama congenital muscular dystrophy and its differentiation from Duchenne muscular dystrophy with severe mental retardation

International Nuclear Information System (INIS)

Toda, Tatsushi; Watanabe, Toshiaki; Shimizu, Teruo; Iwata, Makoto; Kanazawa, Ichiro; Matsumura, Kiichiro.

1993-01-01

Fukuyama congenital muscular dystrophy (FCMD) is the second most common form of muscular dystrophy in Japan and is peculiarly associated with brain anomalies such as micropolygyria. Since these anomalies are preferentially observed on the brain surface, it is difficult to identify them by either X-ray CT or conventional MRI. In addition, FCMD has an atypical (mild) form in which the patients are capable of walking. In such cases, clinical differential diagnosis from Duchenne muscular dystrophy with severe mental retardation (DMD-MR) is not necessarily easy. We analyzed the brain-surface structures of 4 typical FCMD cases. 1 atypical FCMD case, 4 DMD-MR cases, and 1 undiagnosed case using a method of 3-dimensional (3-D) brain-surface MR imaging; we then compared the results with dystrophin immuno-stainings of the biopsied skeletal muscles. In both typical and atypical FCMD cases, micropolygyria could be clearly demonstrated, with individual variations. The 3-D images were verified by neuropathology. Of the 4 DMD-MR cases, 3 cases showed no gyral abnormality. However, in 1 DMD-MR case the diagnosis was corrected to atypical FCMD because of micropolygyria found on 3-D MRI. The one undiangosed case was diagnosed as DMD-MR on the basis of 3-D MRI. There was a good correspondence between the results of the 3-D imaging and the dystrophin test. Recently, some FCMD cases with a complete deficiency of dystrophin have been reported. Therefore, the detection of brain anomalies is important for the precise diagnosis of FCMD; the present method is considered effective for this purpose. (author)

Identification of a gene expression core signature for Duchenne Muscular Dystrophy (DMD) via integrative analysis reveals novel potential compounds for treatment

KAUST Repository

Ichim-Moreno, Norú ; Aranda, Manuel; Voolstra, Christian R.

2010-01-01

Duchenne muscular dystrophy (DMD) is a recessive X-linked form of muscular dystrophy and one of the most prevalent genetic disorders of childhood. DMD is characterized by rapid progression of muscle degeneration, and ultimately death. Currently

Duchenne muscular dystrophy with associated growth hormone deficiency

International Nuclear Information System (INIS)

Ghafoor, T.; Mahmood, A.; Shams, S.

2003-01-01

A patient with duchenne muscular dystrophy (DMD) and growth hormone (GH) deficiency is described who had no clinical evidence of muscular weakness before initiation of GH replacement therapy. Treatment with human GH resulted in appearance of symptoms of easy fatigability and muscle weakness. Thorough investigations including serum creating phosphokinase (CK) levels in recommended in every patient with GH deficiency before starting GH replacement therapy. (author)

Defective myoblasts identified in Duchenne muscular dystrophy.

OpenAIRE

Blau, H M; Webster, C; Pavlath, G K

1983-01-01

A defect in the proliferative capacity of satellite cells, mononucleated precursors of mature muscle fibers, was found in clonal analyses of cells cultured from Duchenne muscular dystrophy (DMD) patients. The total yield of myoblasts per gram of muscle biopsy was decreased to 5% of normal. Of the DMD myoblast clones obtained, a large proportion contained a morphological class of flat distended cells that had an increased generation time and ceased to proliferate beyond 100-1,000 cells but cou...

Dystrophin in frameshift deletion patients with Becker Muscular Dystrophy

Energy Technology Data Exchange (ETDEWEB)

Gangopadhyay, S.B.; Ray, P.N.; Worton, R.G.; Sherratt, T.G.; Heckmatt, J.Z.; Dubowitz, V.; Strong, P.N.; Miller, G. (Penn State College of Medicine, Hershey, PA (United States)); Shokeir, M. (Univ. Hospital, Saskatchewan (Canada))

1992-09-01

In a previous study the authors identified 14 cases with Duchenne muscular dystrophy (DMD) or its milder variant, Becker muscular dystrophy (BMD), with a deletion of exons 3-7, a deletion that would be expected to shift the translational reading frame of the mRNA and give a severe phenotype. They have examined dystrophin and its mRNA from muscle biopsies of seven cases with either mild or intermediate phenotypes. In all cases they detected slightly lower-molecular-weight dystrophin in 12%-15% abundance relative to the normal. By sequencing amplified mRNA they have found that exon 2 is spliced to exon 8, a splice that produces a frameshifted mRNA, and have found no evidence for alternate splicing that might be involved in restoration of dystrophin mRNA reading frame in the patients with a mild phenotype. Other transcriptional and posttranscriptional mechanisms such as cryptic promoter, ribosomal frameshifting, and reinitiation are suggested that might play some role in restoring the reading frame. 34 refs., 5 figs. 1 tab.

RNA interference gene therapy in dominant retinitis pigmentosa and cone-rod dystrophy mouse models caused by GCAP1 mutations

Directory of Open Access Journals (Sweden)

Li eJiang

2014-04-01

Full Text Available RNA interference (RNAi knockdown is an efficacious therapeutic strategy for silencing genes causative for dominant retinal dystrophies. To test this, we used self-complementary (sc AAV2/8 vector to develop an RNAi-based therapy in two dominant retinal degeneration mouse models. The allele-specific model expresses transgenic bovine GCAP1(Y99C establishing a rapid RP-like phenotype, whereas the nonallele-specific model expresses mouse GCAP1(L151F producing a slowly progressing cone/rod dystrophy (CORD. The late onset GCAP1(L151F-CORD mimics the dystrophy observed in human GCAP1-CORD patients. Subretinal injection of scAAV2/8 carrying shRNA expression cassettes specific for bovine or mouse GCAP1 showed strong expression at one week post-injection. In both allele-specific (GCAP1(Y99C-RP and nonallele-specific (GCAP1(L151F-CORD models of dominant retinal dystrophy, RNAi-mediated gene silencing enhanced photoreceptor survival, delayed onset of degeneration and improved visual function. Such results provide a proof of concept toward effective RNAi-based gene therapy mediated by scAAV2/8 for dominant retinal disease based on GCAP1 mutation. Further, nonallele-specific RNAi knockdown of GCAP1 may prove generally applicable toward the rescue of any human GCAP1-based dominant cone-rod dystrophy.

Expression of the Murine Duchenne Muscular Dystrophy Gene in Muscle and Brain

Science.gov (United States)

Chamberlain, Jeffrey S.; Pearlman, Joel A.; Muzny, Donna M.; Gibbs, Richard A.; Ranier, Joel E.; Reeves, Alice A.; Caskey, C. Thomas

1988-03-01

Complementary DNA clones were isolated that represent the 5' terminal 2.5 kilobases of the murine Duchenne muscular dystrophy (Dmd) messenger RNA (mRNA). Mouse Dmd mRNA was detectable in skeletal and cardiac muscle and at a level approximately 90 percent lower in brain. Dmd mRNA is also present, but at much lower than normal levels, in both the muscle and brain of three different strains of dystrophic mdx mice. The identification of Dmd mRNA in brain raises the possibility of a relation between human Duchenne muscular dystrophy (DMD) gene expression and the mental retardation found in some DMD males. These results also provide evidence that the mdx mutations are allelic variants of mouse Dmd gene mutations.

Structure and function of masticatory muscles in a case of muscular dystrophy

DEFF Research Database (Denmark)

Bakke, M; Kirkeby, S; Jensen, B L

1990-01-01

Histologic examination of muscle biopsies and functional examination comprising electromyography and force measurements in a 19-yr-old boy with muscular dystrophy showed different wasting patterns of mandibular elevator and depressor muscles. Pronounced histopathologic changes were present...... depressor strength corresponded more to reference values. This difference of muscular wasting might be caused by protective enzymes in the digastric muscle and/or functionally induced damage of the masseter. As affection from muscular dystrophy may vary greatly between the masticatory muscles, structural...... in the masseter muscle, whereas pathologic findings in the anterior digastric muscle were limited to increased number of cells in slightly enlarged interfiber connective tissue. The masticatory pattern was distorted, and strength of mandibular elevator muscles was less than one third of the norm, whereas...

Defective (U-14 C) palmitic acid oxidation in Duchenne muscular dystrophy

Energy Technology Data Exchange (ETDEWEB)

Carroll, J.E.; Norris, B.J.; Brooke, M.H.

1985-01-01

Compared with normal skeletal muscle, muscle from patients with Duchenne dystrophy had decreased (U-14 C) palmitic acid oxidation. (1-14 C) palmitic acid oxidation was normal. These results may indicate a defect in intramitochondrial fatty acid oxidation.

Defective [U-14 C] palmitic acid oxidation in Duchenne muscular dystrophy

International Nuclear Information System (INIS)

Carroll, J.E.; Norris, B.J.; Brooke, M.H.

1985-01-01

Compared with normal skeletal muscle, muscle from patients with Duchenne dystrophy had decreased [U-14 C] palmitic acid oxidation. [1-14 C] palmitic acid oxidation was normal. These results may indicate a defect in intramitochondrial fatty acid oxidation

Duchenne and Becker Muscular Dystrophy: Contribution of a Molecular and Immunohistochemical Analysis in Diagnosis in Morocco

Directory of Open Access Journals (Sweden)

Hanane Bellayou

2009-01-01

Full Text Available Duchenne muscular dystrophy (DMD and Becker muscular dystrophy (BMD are X-linked recessive disorders caused by mutations of the DMD gene located at Xp21. In DMD patients, dystrophin is virtually absent; whereas BMD patients have 10% to 40% of the normal amount. Deletions in the dystrophin gene represent 65% of mutations in DMD/BMD patients. To explain the contribution of immunohistochemical and genetic analysis in the diagnosis of these dystrophies, we present 10 cases of DMD/BMD with particular features. We have analyzed the patients with immunohistochemical staining and PCR multiplex to screen for exons deletions. Determination of the quantity and distribution of dystrophin by immunohistochemical staining can confirm the presence of dystrophinopathy and allows differentiation between DMD and BMD, but dystrophin staining is not always conclusive in BMD. Therefore, only identification involved mutation by genetic analysis can establish a correct diagnosis.

Health services received by individuals with duchenne/becker muscular dystrophy.

Science.gov (United States)

Pandya, Shree K; Campbell, Kim A; Andrews, Jennifer G; Meaney, F John; Ciafaloni, Emma

2016-02-01

Anecdotal reports from families and care providers suggest a wide variation in services received by individuals with Duchenne/Becker muscular dystrophy (DBMD). We documented the type and frequency of health services received by individuals with DBMD using the Muscular Dystrophy Surveillance Tracking and Research Network (MD STARnet) interview data released in June 2012. Interviews with eligible caregivers from 5 sites (Arizona, Colorado, Georgia, Iowa, and western New York) were conducted from April 2007 to March 2012. Two hundred ninety-six caregivers (66% of those contactable) participated in the interview. There were significant differences among sites in the specialists seen and services received. Concurrence with cardiac recommendations was higher than that with respiratory recommendations. The results of this survey support and quantify the anecdotal reports from families and care providers regarding the disparities in services received by individuals with DBMD. It remains to be determined whether these differences affect outcomes. © 2015 Wiley Periodicals, Inc.

Drugs in development and dietary approach for Duchenne muscular dystrophy

Directory of Open Access Journals (Sweden)

Angelini C

2015-08-01

Full Text Available Corrado Angelini, Elisabetta Tasca Neuromuscular Laboratory, Fondazione San Camillo Hospital IRCCS, Venice, Italy Abstract: Therapeutic trials studying Duchenne muscular dystrophy (DMD in Europe and the USA have been done using a protocol that includes manual muscle testing and functional testing, and have shown the efficacy of steroid drugs in various doses and regimens. Further, drisapersen and eteplirsen (exon skipping drugs and ataluren (a drug to overcome stop codon mutations have achieved some clinical improvement. Cardioprotective drugs are efficacious in DMD, and eplerenone, an aldosterone inhibitor and diuretic, is now being used to treat the disease. The dietary approach should be used in wheelchair-bound DMD children in combination with respiratory assistance. The importance of some of the treatments proposed is that they might also be useful in other genetic disorders where stop codon mutations are present; moreover, it is possible that these new treatments will improve quality of life for many patients. Keywords: Duchenne muscular dystrophy, steroids, ataluren, drisapersen, eplerenone, eteplirsen

Socio-economic characteristics of patients with generalized retinal dystrophy in Denmark

DEFF Research Database (Denmark)

Bertelsen, Mette; Linneberg, Allan; Rosenberg, Thomas

2015-01-01

the Danish Retinitis Pigmentosa Registry and 228,500 control subjects matched by age and gender. Demographic and socio-economic data were retrieved from Statistics Denmark. Differences between cases and controls were estimated using conditional logistic regression. RESULTS: On 1 January 2012, 2285 patients......PURPOSE: To examine socio-economic characteristics of patients with generalized retinal dystrophy in Denmark. METHODS: Cross-sectional population-based study with analysis of socio-economic characteristics including income, education, employment status and civil status in 2285 patients from...... with a Danish civil registration number were registered as having a generalized retinal dystrophy. At the age of 40 years, less patients than controls had a high education (odds ratio (OR), 0.51; 95% confidence interval (CI95), 0.41-0.62), a high income (OR, 0.21; CI95, 0.17-0.26) and were married (OR, 0.39; CI...

Intermittent prednisone therapy in Duchenne muscular dystrophy : A randomized controlled trial

NARCIS (Netherlands)

Beenakker, EAC; Fock, JM; Van Tol, M; Maurits, NM; Koopman, HM; Brouwer, OF; Van der Hoeven, JH

Background: Prednisone treatment is used to prolong ambulation in patients with Duchenne muscular dystrophy (DMD). However, since severe adverse effects often accompany prednisone treatment, it is debatable whether the benefits of prednisone treatment outweigh its adverse effects. Objectives: To

Becker muscular dystrophy with widespread muscle hypertrophy and a non-sense mutation of exon 2

DEFF Research Database (Denmark)

Witting, Nanna; Duno, M; Vissing, J

2013-01-01

Becker muscular dystrophy features progressive proximal weakness, wasting and often focal hypertrophy. We present a patient with pain and cramps from adolescence. Widespread muscle hypertrophy, preserved muscle strength and a 10-20-fold raised CPK were noted. Muscle biopsy was dystrophic......, and Western blot showed a 95% reduction of dystrophin levels. Genetic analyses revealed a non-sense mutation in exon 2 of the dystrophin gene. This mutation is predicted to result in a Duchenne phenotype, but resulted in a mild Becker muscular dystrophy with widespread muscle hypertrophy. We suggest...

Implicit learning deficit in children with Duchenne muscular dystrophy: Evidence for a cerebellar cognitive impairment?

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Vicari, Stefano; Piccini, Giorgia; Mercuri, Eugenio; Battini, Roberta; Chieffo, Daniela; Bulgheroni, Sara; Pecini, Chiara; Lucibello, Simona; Lenzi, Sara; Moriconi, Federica; Pane, Marika; D'Amico, Adele; Astrea, Guja; Baranello, Giovanni; Riva, Daria; Cioni, Giovanni; Alfieri, Paolo

2018-01-01

This study aimed at comparing implicit sequence learning in individuals affected by Duchenne Muscular Dystrophy without intellectual disability and age-matched typically developing children. A modified version of the Serial Reaction Time task was administered to 32 Duchenne children and 37 controls of comparable chronological age. The Duchenne group showed a reduced rate of implicit learning even if in the absence of global intellectual disability. This finding provides further evidence of the involvement of specific aspects of cognitive function in Duchenne muscular dystrophy and on its possible neurobiological substrate.