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Duchenne muscular dystrophy (DMD) is a devastating X-linked neuromuscular disorder caused by dystrophin gene deletions (75%), duplications (15-20%) and point mutations (5-10%), a small portion of which are nonsense mutations. Women carrying dystrophin gene mutations are commonly unaffected because the wild X allele may produce a sufficient amount of the dystrophin protein. However, approximately 8-10% of them may experience muscle symptoms and 50% of those over 40 years develop cardiomyopathy. The presence of symptoms defines the individual as an affected "symptomatic or manifesting carrier". Though there is no effective cure for DMD, therapies are available to slow the decline of muscle strength and delay the onset and progression of cardiac and respiratory impairment. These include ataluren for patients with nonsense mutations, and antisense oligonucleotides therapies, for patients with specific deletions. Symptomatic DMD female carriers are not included in these indications and little data documenting their management, often entrusted to the discretion of individual doctors, is present in the literature. In this article, we report the clinical and instrumental outcomes of four symptomatic DMD carriers, aged between 26 and 45 years, who were treated with ataluren for 21 to 73 months (average 47.3), and annually evaluated for muscle strength, respiratory and cardiological function. Two patients retain independent ambulation at ages 33 and 45, respectively. None of them developed respiratory involvement or cardiomyopathy. No clinical adverse effects or relevant abnormalities in routine laboratory values, were observed.
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Cardiomiopatías , Distrofia Muscular de Duchenne , Oxadiazoles , Humanos , Femenino , Preescolar , Distrofina/genética , Proyectos Piloto , Codón sin Sentido , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapiaRESUMEN
Duchenne muscular dystrophy (DMD) is a neuromuscular condition characterized by muscle weakness. The Performance of upper limb (PUL) test is designed to evaluate upper limb function in DMD patients across three domains. The aim of this study is to identify frequently lost or gained PUL 2.0 abilities at distinct functional stages in DMD patients. This retrospective study analyzed prospectively collected data on 24-month PUL 2.0 changes related to ambulatory function. Ambulant patients were categorized based on initial 6MWT distance, non-ambulant patients by time since ambulation loss. Each PUL 2.0 item was classified as shift up, no change, or shift down. The study's cohort incuded 274 patients, with 626 paired evaluations at the 24-month mark. Among these, 55.1 % had activity loss, while 29.1 % had gains. Ambulant patients showed the lowest loss rates, mainly in the shoulder domain. The highest loss rate was in the shoulder domain in the transitioning subgroup and in elbow and distal domains in the non-ambulant patients. Younger ambulant patients demonstrated multiple gains, whereas in the other functional subgroups there were fewer gains, mostly tied to singular activities. Our findings highlight divergent upper limb domain progression, partly linked to functional status and baseline function.
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Distrofia Muscular de Duchenne , Humanos , Distrofia Muscular de Duchenne/complicaciones , Estudios Retrospectivos , Extremidad Superior , Caminata , Debilidad MuscularRESUMEN
The contiguous gene deletion syndromes (CGDS) are rare genomic disorders resulting from the deletion of large segments of DNA, manifested as the concurrence of apparently unrelated clinical features. A typical example of CGDS is Xp21 contiguous gene deletion syndrome that involves GK and its neigh-boring genes (usually DMD and NR0B1) and results in a complex phenotype, which is related to the size of deletion and involved genes. Development delay and intellectual disability are almost a constant feature of patients with CGDS. We report the case of a boy with Duchenne muscular dystrophy (DMD) and glycerol kinase deficiency (GKD) as part of the contiguous gene deletion syndrome Xp2.1, in association with intellectual disability (ID) in whom multiplex ligation-dependent probe amplification (MLPA) test first identified a hemizygous deletion involving the entire dystrophin gene. Subsequently, the array CGH study identified a maternally inherited hemizygous deletion of the Xp21.2-Xp21.1 region of approximately 3.7Mb that included both DMD and GK genes confirming the diagnosis of Xp21 CGDS. Moreover, we report a review of the cases published in the literature over the last 20 years, for which a better description of the genes involved in the syndrome was available. Intellectual disability does not appear as a constant feature of the syndrome, reiterating the concept that complex GKD syndrome results from small deletions that affect closely related but separate loci for DMD, GK and adrenal hypoplasia, rather than a single large deletion including all genes. This case highlights the importance of more in-depth genetic investigations in presence of apparently unrelated clinical findings, allowing an accurate diagnosis of contiguous gene deletion syndromes.
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Discapacidad Intelectual , Distrofia Muscular de Duchenne , Humanos , Distrofia Muscular de Duchenne/complicaciones , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/genética , Insuficiencia Corticosuprarrenal Familiar/genética , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Glicerol Quinasa/genética , Eliminación de GenRESUMEN
Dystrophinopathies are X-linked recessive muscle disorders caused by mutations in the dystrophin (DMD) gene that include deletions, duplications, and point mutations. Correct diagnosis is important for providing adequate patient care and family planning, especially at this time when mutation-specific therapies are available. We report a large single-centre study on the spectrum of DMD gene variants observed in 750 patients analyzed for suspected Duchenne (DMD) or Becker (BMD) muscular dystrophy, over the past 30 years, at the Cardiomyology and Medical Genetics of the University of Campania. We found 534 (71.21%) large deletions, 73 (9.73%) large duplications, and 112 (14.93%) point mutations, of which 44 (5.9%) were small ins/del causing frame-shifts, 57 (7.6%) nonsense mutations, 8 (1.1%) splice site and 3 (0.4%) intronic mutations, and 31 (4.13%) non mutations. Moreover, we report the prevalence of the different types of mutations in patients with DMD and BMD according to their decade of birth, from 1930 to 2020, and correlate the data to the different techniques used over the years. In the most recent decades, we observed an apparent increase in the prevalence of point mutations, probably due to the use of Next-Generation Sequencing (NGS). In conclusion, in southern Italy, deletions are the most frequent variation observed in DMD and BMD patients followed by point mutations and duplications, as elsewhere in the world. NGS was useful to identify point mutations in cases of strong suspicion of DMD/BMD negative on deletions/duplications analyses. In the era of personalized medicine and availability of new causative therapies, a collective effort is necessary to enable DMD and BMD patients to have timely genetic diagnoses and avoid late implementation of standard of care and late initiation of appropriate treatment.
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Distrofina , Distrofia Muscular de Duchenne , Humanos , Distrofina/genética , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/genética , Estudios Retrospectivos , Exones , MutaciónRESUMEN
Myotonic Dystrophy type 1 (DM1) is the most common muscular dystrophy in adults, affecting 1:8000 individuals. It is a multi-systemic disorder involving muscle, heart, endocrine and respiratory apparatus and eye. The eye symptoms can include ptosis, external ophthalmoplegia, epiphora, and early onset cataracts. Cataracts occur at a much earlier age (usually between 30 and 40) than the general population, where females are usually affected more than men. We studied gender differences in cataract prevalence and treatment age in 243 DM1 patients (134 M; 109 F), aged 18 to 70 years, who were subsequently screened at routine follow-up. For each patient, information was collected on age, sex, CTG expansion, age of cataract onset, and age at cataract surgery, when available. Seventy-three patients, 30 females and 43 males, had cataracts, at a mean age of onset of 41.14 ± 12.64 in females, and 40.36 ± 10.03 in males. Sixty-nine of them underwent cataract surgery, males at an earlier age than females (42.8 ± 9.8 years versus 47.3 ± 12.6 years) and in 52.5% of cases before the age of 40, compared to 17.2% of females. The difference was statistically significant. The assumption that females in general and those with DM1 in particular develop cataracts more frequently and earlier than males is not confirmed, at least in this study. A possible explanation for these results could be related to non-advanced age, the protective role of estrogen and the lower prevalence of smoking in the study population.
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Extracción de Catarata , Catarata , Distrofias Musculares , Distrofia Miotónica , Adulto , Masculino , Femenino , Humanos , Distrofia Miotónica/complicaciones , Distrofia Miotónica/epidemiología , Distrofia Miotónica/diagnóstico , Prevalencia , Catarata/epidemiología , Catarata/etiologíaRESUMEN
[This retracts the article DOI: 10.36185/2532-1900-058.].
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Progressive cardiac conduction disease (PCCD) is a relatively common condition in young and elderly populations, related to rare mutations in several genes, including SCN5A, SCN1B, LMNA and GJA5, TRPM4. Familial cases have also been reported. We describe a family with a large number of individuals necessitating pacemaker implantation, likely due to varying degrees of PCCD. The proband is a 47-year-old-patient, whose younger brother died at 25 years of unexplained sudden cardiac death. Three paternal uncles needed a pacemaker (PM) implantation between 40 and 65 years for unspecified causes. At the age of 42, he was implanted with a PM for two episodes of syncope and the presence of complete atrioventricular block (AVB). NGS analysis revealed the missense variation c. 2351G>A, p.Gly844Asp in the exon 17 of the TRPM4 gene. This gene encodes the TRPM4 channel, a calcium-activated nonselective cation channel of the transient receptor potential melastatin (TRPM) ion channel family. Variations in TRPM4 have been shown to cause an increase in cell surface current density, which results in a gain of gene function. Our report broadens and supports the causative role of TRPM4 gene mutations in PCCD. Genetic screening and identification of the causal mutation are critical for risk stratification and family counselling.
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Bloqueo Atrioventricular , Canales Catiónicos TRPM , Anciano , Bloqueo Atrioventricular/genética , Bloqueo Atrioventricular/metabolismo , Muerte Súbita Cardíaca , Corazón , Humanos , Masculino , Persona de Mediana Edad , Mutación , Canales Catiónicos TRPM/genética , Canales Catiónicos TRPM/metabolismoRESUMEN
Duchenne's muscular dystrophy (DMD) is an X-linked neuromuscular disorder caused by deletions (75%), duplications (15-20%) and point mutations (5-10%) in the dystrophin gene. Among the latter, stop-codon point mutations are rare. Female carriers of dystrophin gene mutations are usually asymptomatic as they are "protected" by the second X-chromosome, which produces a normal dystrophin protein. However, about 8-10% of them can present symptoms that set the clinical picture of the manifesting or symptomatic carrier. Although no causative cure there is for DMD, therapies are available to slow the decline of muscle weakness and delay the onset of heart and respiratory involvement. However, there is limited data in the literature documenting the treatment of symptomatic carriers, often entrusted to the sensitivity of individual doctors. In this paper, we report the follow-up outcomes of four European symptomatic nmDMD carriers treated with ataluren, overall followed for 193 months. Annual assessment of muscle strength, pulmonary lung function tests, and echocardiography, indicate a mild attenuation of disease progression under treatment.. There were no adverse clinical effects or relevant abnormalities in routine laboratory tests. We can conclude that ataluren appears to stabilize, if not slightly improve, the clinical course of patients with a good safety profile, especially if we consider that the treatment was late for 3/4 patients, at a mean age of 36.6 ± 10.6 years.
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Distrofia Muscular de Duchenne , Oxadiazoles , Adulto , Distrofina/genética , Femenino , Estudios de Seguimiento , Humanos , Persona de Mediana Edad , Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/terapia , MutaciónRESUMEN
Myotonic dystrophy (DM1) is the most common muscle disease in adults, affecting approximately 1:8000 individuals, characterized by myotonia and muscular wasting and a multisystemic involvement that includes heart, brain, respiratory and endocrine system, and eye. Conduction system is selectively involved, often causing cardiac sudden death. Early onset posterior subcapsular cataract is a characteristic feature of myotonic dystrophy, requiring surgical treatment. However, DM1 is associated with many anesthetic hazards; sensitivity to anesthetic drugs, especially muscle relaxants and opioids, may complicate postoperative care. Local anesthesia also requires attention. We investigated the heart response to local anesthesia Ropivacaine Hcl administration in 16 DM1 patients (12M:4F) consecutively undergoing cataract surgery, by analyzing heart rate, ventricular and supraventricular ectopic beats, runs of tachycardia and pauses ≥ 2.5 sec., through a 24h-Holter monitoring, registered before and within 24 hours after surgery. The average age of patients was 47.4 years (range 30.2-55.9). At baseline, one patient had a pacemaker and 3 a defibrillator. Two patients presented a first-degree atrio-ventricular-block; three showed ectopic ventricular beats, on anti-arrhythmic drug treatment. No significant differences in heart rate values (73 ± 15b/m versus 76 ± 13b/m) were observed after cataract surgery, nor in the onset of ectopic beats. Only patients who presented ventricular ectopic beats at baseline, showed an increase in their number after surgery, likely related to an arbitrary interruption of the specific treatment. These data confirm the safety and efficacy of ropivacaine HCl used as a local anesthetic in patients with myotonic dystrophy.
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Anestesia Local , Anestésicos Locales/uso terapéutico , Extracción de Catarata , Catarata/complicaciones , Distrofia Miotónica/complicaciones , Ropivacaína/uso terapéutico , Adulto , Catarata/fisiopatología , Estudios de Cohortes , Electrocardiografía Ambulatoria , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Distrofia Miotónica/fisiopatologíaRESUMEN
INTRODUCTION: Since February 2020, the outbreak of COVID-19 in Italy has forced the health care system to undergo profound rearrangements in its services and facilities, especially in the worst-hit areas in Northern Italy. In this setting, inpatient and outpatient services had to rethink and reorganize their activities to meet the needs of patients during the "lockdown". The Italian Association of Myology developed a survey to estimate the impact of these changes on patients affected by neuromuscular disorders and on specialized neuromuscular centers during the acute phase of COVID-19 pandemic. METHODS: We developed an electronic survey that was sent to neuromuscular centers affiliated with the Italian Association of Myology, assessing changes in pharmacological therapies provision, outpatient clinical and instrumental services, support services (physiotherapy, nursing care, psychological support) and clinical trials. RESULTS: 40% of surveyed neuromuscular centers reported a reduction in outpatient visit and examinations (44.5% of centers in Northern regions; 25% of centers in Central regions; 50% of centers in Southern regions). Twenty-two% of centers postponed in-hospital administration of therapies for neuromuscular diseases (23.4% in Northern regions; 13.0% in Central regions; 20% in Southern regions). Diagnostic and support services (physiotherapy, nursing care, psychological support) were suspended in 57% of centers (66/43/44% in Northern, Central and Southern centers respectively) Overall, the most affected services were rehabilitative services and on-site outpatient visits, which were suspended in 93% of centers. Strategies adopted by neuromuscular centers to overcome these changes included maintaining urgent on-site visits, addressing patients to available services and promoting remote contact and telemedicine. CONCLUSIONS: Overall, COVID-19 pandemic resulted in a significant disruption of clinical and support services for patients with neuromuscular diseases. Despite the efforts to provide telemedicine consults to patients, this option could be promoted and improved further. A close collaboration between the different neuromuscular centers and service providers as well as further implementation of telehealth platforms are necessary to ensure quality care to NMD patients in the near future and in case of recurrent pandemic waves.
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Betacoronavirus , Infecciones por Coronavirus/epidemiología , Accesibilidad a los Servicios de Salud/organización & administración , Enfermedades Neuromusculares/terapia , Neumonía Viral/epidemiología , Derivación y Consulta/organización & administración , Telemedicina/organización & administración , Atención Ambulatoria , COVID-19 , Infecciones por Coronavirus/prevención & control , Estudios Transversales , Hospitalización , Humanos , Italia/epidemiología , Pandemias/prevención & control , Neumonía Viral/prevención & control , SARS-CoV-2 , Encuestas y CuestionariosRESUMEN
Myotonia congenita is a genetic disease characterized by impaired muscle relaxation after forceful contraction (myotonia). It is caused by mutations in the CLCN1 gene, encoding the voltage-gated chloride channel of skeletal muscle, ClC-1. According to the pattern of inheritance, two distinct clinical forms have been described, Thomsen disease, inherited as an autosomal dominant trait and Becker disease inherited as an autosomal recessive trait. We report genetic and clinical data concerning 19 patients-13 familial and six isolated cases-all but one originating from the Campania Region, in southern Italy. Twelve patients (63.2%) present Becker type myotonia and 7 (36.8%) Thomsen type. Sex ratio M:F in Becker type is 6:6, while in Thomsen myotonia 4:3. The age of onset of the disease ranged from 2 to 15 years in Becker patients, and from 4 to 20 years in Thomsen. Overall 18 mutations were identified, 10 located in the coding part of the gene (exons 1, 3, 4, 5, 7, 8, 13, 15, 21, 22), and four in the intron part (introns 1, 2, 10, 18). All the exon mutations but two were missense mutations. Some of them, such as c.2551 G > A, c.817G > A and c.86A > C recurred more frequently. About 70% of mutations was inherited with an autosomal recessive pattern, two (c.86A and c.817G>A) with both mechanisms. Three novel mutations were identified, never described in the literature: p.Gly276Ser, p.Phe486Ser, and p.Gln812*, associated with Becker phenotype. Furthermore, we identified three CLCN1 mutations-c.86A>C + c.2551G > A, c.313C > T + c.501C > G and 899G > A + c.2284+5C > T, two of them inherited in cis on the same allele, in three unrelated families. The concomitant occurrence of both clinical pictures-Thomsen and Becker-was observed in one family. Intra-familial phenotypic variability was observed in two families, one with Becker phenotype, and one with Thomsen disease. In the latter an incomplete penetrance was hypothesized.
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Facioscapulohumeral muscular dystrophy (FSHD) is a neuromuscular disorder which is typically transmitted by an autosomal dominant pattern, although reduced penetrance and sporadic cases caused by de novo mutations, are often observed. FSHD may be caused by a contraction of a repetitive element, located on chromosome 4 (4q35). This locus is named D4Z4 and consists of 11 to more than 100 repeated units (RU). The D4Z4 is normally hypermethylated and the genes located on this locus are silenced. In case of FSHD, the D4Z4 region is characterized by 1-10 repeats and results in the region being hypomethylated. However, 5% of FSHD cases do not carry the short allele of D4Z4 region. To date, two forms of FSHD (FSHD1 and FSHD2) are known. FSHD2 is usually observed in patients without the D4Z4 fragment contraction and carrying variants in SMCHD1 (18p11.32) gene. We report the case of a young adult patient who shows severe symptoms of FSHD. Preliminary genetic analysis did not clarify the phenotype, therefore we decided to study the family members by genetic and epigenetic approaches. The analysis of D4Z4 fragment resulted to be 8 RU in the affected proband and in his father; 26 RU in the mother and 25 RU in the maternal uncle. SMCHD1 analysis revealed a heterozygous variation within the exon 41. The variant was detected in the proband, her mother and the uncle. Furthermore, epigenetic analysis of CpG6 methylation regions showed significant hypomethylation in the affected patient (54%) and in the mother (56%), in contrast to the father (88%) and the uncle (81%) carrying higher methylation levels. The analysis of DR1 methylation levels reported hypomethylation for the proband (19%), the mother (11%), and the uncle (16%). The father showed normal DR1 methylation levels (>30%). Given these results, the combined inheritance of SMCHD1 variant and the short fragment might explain the severe FSHD phenotype displayed by the proband. On this subject, SMCHD1 analysis should be promoted in a larger number of patients, even in presence of D4Z4 contractions, to facilitate the genotype-phenotype correlation as well as, to enable a more precise diagnosis and prognosis of the disease.
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The aim of the study was to establish 24 month changes in upper limb function using a revised version of the performance of upper limb test (PUL 2.0) in a large cohort of ambulant and non-ambulant boys with Duchenne muscular dystrophy and to identify possible trajectories of progression. Of the 187 patients studied, 87 were ambulant (age range: 7-15.8 years), and 90 non-ambulant (age range: 9.08-24.78). The total scores changed significantly over time (p<0.001). Non-ambulant patients had lower total scores at baseline (mean 19.7) when compared to the ambulant ones (mean 38.4). They also had also a bigger decrease in total scores over 24 months compared to the ambulant boys (4.36 vs 2.07 points). Multivariate model analysis showed that the Performance of Upper Limb changes reflected the entry level and ambulation status, that were independently associated to the slope of Performance of Upper Limb changes. This information will be of help both in clinical practice and at the time of designing clinical trials.
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Distrofia Muscular de Duchenne/fisiopatología , Extremidad Superior/fisiopatología , Adolescente , Niño , Progresión de la Enfermedad , Humanos , Estudios Longitudinales , Masculino , Monitoreo AmbulatorioRESUMEN
Myotonic dystrophy type 1 (DM1) or Steinert's disease is the most common muscular dystrophy in adult life with an estimated prevalence of 1:8000. Cardiac involvement, including arrhythmias and conduction disorders, contributes significantly to the morbidity and mortality of the disease. Mild ventricular dysfunction has also been reported associated with conduction disorders, but severe ventricular systolic dysfunction is not a frequent feature and usually occurs late in the course of the disease. Heart transplantation is currently considered the ultimate gold standard surgical approach in the treatment of refractory heart failure in general population. To date, considering the shortage of donors that limit the achievement of a greater number of heart transplants and the reluctance of the cardiac surgeons to transplant patients with dystrophic cardiomyopathy, little is known about the number of patients with DM1 transplanted and their outcome. We report the case of a 44 year old patient with Steinert disease who showed an early onset ventricular dysfunction refractory to optimal medical and cardiac resincronization therapy, and underwent to successful heart transplantation. At our knowledge, this is the second heart transplantation performed in a patient affected by Steinert disease after the one reported by Conraads et al in 2002.
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Cardiomiopatía Dilatada , Insuficiencia Cardíaca , Trasplante de Corazón/métodos , Distrofia Miotónica , Adulto , Cardiomiopatía Dilatada/diagnóstico , Cardiomiopatía Dilatada/etiología , Cardiomiopatía Dilatada/fisiopatología , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/cirugía , Ventrículos Cardíacos/fisiopatología , Humanos , Italia , Masculino , Distrofia Miotónica/diagnóstico , Distrofia Miotónica/fisiopatología , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
This paper describes the psycho-social treatments received by 502 patients with MDs and their relatives, and the costs for care sustained by the families in the previous six month period. Data were collected by the MD-Care Schedule (MD-CS) and the Family Problems Questionnaire (FPQ). Psycho-educational interventions were provided to 72 patients (14.3%), and social/welfare support to 331 patients (65.9%). Social/welfare support was higher in patients with DMD or LGMD, in those showing more severe disability, and in patients who were in contact with centres located in Northern Italy. Psycho-educational interventions were received by 156 (31%) relatives, and social/welfare support by 55 (10.9%) and mainly provided by Family/Patients Associations (83.6%). Relatives with higher educational levels, who spent more daily hours in the assistance of patients with DMD, and in contact with centres in Central Italy more frequently benefited from psycho-educational interventions. In the previous year, costs for care were sustained by 314 (63.9%) relatives. Financial difficulties related to patient's condition, were higher in families of patients who needed more intensive rehabilitation and daily hours of caregiving, and in families who lived further away from the reference's centre. These results showed that psycho-social aspects of MDs care are only partially met in Italy, and that ad hoc supportive interventions for these patients and their families should be potentiated.
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Cuidadores/psicología , Costo de Enfermedad , Distrofias Musculares/economía , Distrofias Musculares/psicología , Sistemas de Apoyo Psicosocial , Bienestar Social , Actividades Cotidianas , Adolescente , Adulto , Niño , Preescolar , Prestación Integrada de Atención de Salud , Honorarios y Precios/estadística & datos numéricos , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Distrofias Musculares/rehabilitación , Educación del Paciente como Asunto , Adulto JovenRESUMEN
This paper describes the pharmacological therapies and rehabilitative interventions received by 502 patients with Muscular Dystrophies, evaluated in relation to patient's socio-demographic and clinical variables, and geographical areas. Data were collected by the MD-Socio-Demographic and Clinical Schedule (MD-SC-CS) and by the Family Problems Questionnaire (FPQ). The most part of the enrolled patients were in drug treatment. The number of the medications increased in relation to patient's age, disability degree and duration of illness and was higher among patients with Duchenne Muscular Dystrophy (DMD) compared with Becker (BMD) or Limb-Girdle Muscular Dystrophies (LGMD). Steroids (deflazacort or prednisone) were the drug most frequently used, followed by cardiologic and bone metabolism drugs. In general, patients using steroids were younger and had a shorter duration of illness; patients using cardiac drugs and dietary supplements were older and had a longer duration of illness. Rehabilitative interventions were provided to about 70% (351/502) of patients, mainly DMD. Of these, physiotherapy was the more frequent treatment (96.6%) and was prevalently performed in rehabilitative centres (about 70% of patients) and at home in only 30%. Hydrokinetic-therapy was practiced by 6.8% of patients. Respiratory rehabilitation was provided to 47.0% of patients (165/351) and assisted mechanical ventilaventilation to 13.1% (46). The amount of rehabilitative interventions increased in relation to the patient's age, level of disability and duration of illness. Compared to Central and Northern Italy, in Southern Italy there was a higher attention to cardiological impairment as shown by a higher number of patients receiving heart drugs. No statistically significant differences concerning the possibility to have access to rehabilitative interventions were noted among the three geographical areas. However, patient living in Southern Italy tend to receive rehabilitation more often at home.
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Glucocorticoides/uso terapéutico , Distrofias Musculares/tratamiento farmacológico , Distrofias Musculares/rehabilitación , Modalidades de Fisioterapia , Adolescente , Factores de Edad , Conservadores de la Densidad Ósea/uso terapéutico , Ejercicios Respiratorios , Cardiotónicos/uso terapéutico , Niño , Terapia Combinada , Suplementos Dietéticos , Evaluación de la Discapacidad , Femenino , Encuestas de Atención de la Salud , Humanos , Italia , Masculino , Prednisona/uso terapéutico , Pregnenodionas/uso terapéutico , Respiración Artificial , Factores de TiempoRESUMEN
Despite all the advances in diagnosis and management of Duchenne muscular dystrophy over the past 50 years, the average age at diagnosis in most countries in the world around is still around 4-5 years. This retrospective study investigates the age at diagnosis in Italy in the past 10 years. We report findings from 384 boys who were diagnosed with DMD from 2005 to 2014. The mean age at first medical contact, which raised the suspicion of DMD, was 31 months. The mean age at diagnosis was 41 months. The finding that more frequently brought to suspect a DMD was the incidental finding of consistent elevated creatine kinase serum level detected during routine assessments in children undergoing general anesthesia or with intercurrent illness. This was followed by motor delay and signs of muscle weakness. Initial concerns were raised by general pediatricians (29%), specialists at tertiary centers (35%) or first level hospitals (23%). In children presenting incidental elevated creatine kinase values the diagnosis was achieved earlier than in children presenting a developmental delay. The mean age at diagnosis in our cohort was about 10-12 months lower than that reported in other countries.
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Distrofia Muscular de Duchenne/diagnóstico , Biomarcadores/metabolismo , Niño , Preescolar , Creatina Quinasa/metabolismo , Diagnóstico Tardío , Discapacidades del Desarrollo/diagnóstico , Discapacidades del Desarrollo/fisiopatología , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Humanos , Lactante , Recién Nacido , Italia , Masculino , Músculos/patología , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/patología , Distrofia Muscular de Duchenne/fisiopatología , Mejoramiento de la CalidadRESUMEN
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.
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Arritmias Cardíacas/terapia , Desfibriladores Implantables , Distrofia Miotónica/complicaciones , Implantación de Prótesis/métodos , Disfunción Ventricular Izquierda/terapia , Disfunción Ventricular Derecha/terapia , Adulto , Arritmias Cardíacas/etiología , Terapia de Resincronización Cardíaca , Insuficiencia Cardíaca/etiología , Insuficiencia Cardíaca/terapia , Humanos , Masculino , Distrofia Miotónica/fisiopatología , Disfunción Ventricular Izquierda/etiología , Disfunción Ventricular Derecha/etiologíaRESUMEN
In Duchenne muscular dystrophy (DMD) little has been reported on the association between clinical outcome measures and patient health-related quality of life (HRQOL) tools. Our study evaluated the relationship between 12 month changes on the Generic Core Scales (GCS), the Multidimensional Fatigue Scale and the Neuromuscular Module of the PedsQL(TM) with several outcome measures (6 minute walk test, North Star Ambulatory Assessment and timed items) in ambulatory DMD. Ninety-eight ambulatory DMD in a multicentric setting were included in the study. At baseline, the PedsQL(TM) inventories correlated with almost all the functional measures On the Child Self-Report there was a significant decrease between baseline and 12 months on the PedsQL(TM) GCS and its first domain, in parallel with the decrement in the functional outcome measures. Correlation between the 12 month changes on the PedsQL(TM) inventories and functional measures were almost all negligible. Similar results were obtained on the Parent Proxy-Report. In conclusion, PedsQL(TM) correlates with the level of impairment at baseline, but this does not hold true when 12 month changes are considered. Further studies comparing different tools are needed to better elucidate the complexity of the relationship between HRQOL and functional performances.
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Distrofia Muscular de Duchenne/diagnóstico , Distrofia Muscular de Duchenne/psicología , Calidad de Vida , Adolescente , Niño , Preescolar , Fatiga/diagnóstico , Fatiga/etiología , Humanos , Estudios Longitudinales , Masculino , Distrofia Muscular de Duchenne/complicaciones , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Encuestas y CuestionariosRESUMEN
Muscular dystrophies are a group of genetic disorders characterized by muscle degeneration and consequent substitution by fat and fibrous tissue. Cardiac involvement is an almost constant feature in a great part of these diseases, as both primary myocardial involvement and secondary involvement due to respiratory insufficiency, pulmonary hypertension or reduced mobility. Primary myocardial involvement usually begins more precociously compared to the secondary involvement. In fact the first signs of cardiomyopathy can be observed in the first decade of life in muscular dystrophies with childhood onset and later in adult form of muscular dystrophies as myotonic dystrophy type 1. At least an annual cardiac follow-up is recommended in these patients including clinical and instrumental examination (ECG, 24h Holter monitoring, ECHO), to detect cardiac involvement. A more frequent monitoring may be required according to the type of cardiomyopathy and the patient's needs. In this short review practical guide-lines are shown for physicians routinely involved in the management of these patients.