RESUMEN
Myotonic dystrophy type 2 (DM2) lacks validated patients´ reported outcomes (PROs). This represents a limit for monitoring disease progression and perceived efficacy of symptomatic treatments. Our aim was to investigate whether PROs for activities of daily living designed for other neuromuscular diseases could be used in DM2. Sixty-six DM2 patients completed the following PROs: DM1-Activ-c, Rasch-built Pompe-specific activity (R-PAct) scale, McGill-pain questionnaire, fatigue and daytime sleepiness scale and Beck depression inventory (BDI-II). Clinical data and motor outcome measures (6-minutes walking test - 6MWT, manual muscle testing, quick motor function test and myotonia behavior scale) were collected as well. Patients underwent one visit at baseline and one after 10 months. Ceiling/flooring effects, criterion validity and discriminant validity were calculated. DM1-activ-c and R-PAct showed acceptable ceiling effects despite being built for myotonic dystrophy type 1 and Pompe disease, respectively. The difficulty hierarchy of the single items was better preserved in R-PAct than in DM1-Activ-c. Both tests showed excellent criterion validity highly correlating with 6MWT, quick motor function test, myalgia and disease duration. They could partially discriminate patients with different disability grades. These results suggest that DM1-Activ-c, slightly better than R-PAct, might be adopted for monitoring activities of daily living also in DM2, at least until disease-specific PROs will be available.
Asunto(s)
Actividades Cotidianas , Distrofia Miotónica/diagnóstico , Distrofia Miotónica/fisiopatología , Medición de Resultados Informados por el Paciente , Psicometría/normas , Sistema de Registros , Índice de Severidad de la Enfermedad , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Distrofia Miotónica/terapia , Reproducibilidad de los ResultadosRESUMEN
Hyper-reflexia is occasionally seen in acute motor axonal neuropathy (AMAN), but its pathophysiology is unclear. We report a patient with AMAN following Campylobacter jejuni enteritis, who showed generalized hyper-reflexia, bilateral Hoffmann sign and right Babinski sign. MRI and transcranial magnetic stimulation of the motor cortex disclosed no corticospinal tract involvement. An extensive electrophysiological investigation documented α-motoneuron hyperexcitability and dysfunction of the interneuronal inhibitory circuits in the spinal anterior horn. We propose an immune-mediated damage of the spinal inhibitory interneuronal network as possible mechanism inducing hyper-reflexia in AMAN.
Asunto(s)
Células del Asta Anterior/fisiología , Infecciones por Campylobacter/complicaciones , Síndrome de Guillain-Barré/fisiopatología , Reflejo Anormal/fisiología , Adulto , Potenciales Evocados Motores , Femenino , Síndrome de Guillain-Barré/etiología , Humanos , Masculino , Persona de Mediana Edad , Corteza Motora/fisiopatología , Conducción Nerviosa , Reflejo Anormal/inmunología , Estimulación Magnética TranscranealRESUMEN
Introduction: Myotonic dystrophy type 2 (DM2) lacks disease-specific, validated, motor outcome measures (OMs), and patients' reported outcomes (PROs). This represents a limit for the monitoring of disease progression and treatment response. Our aim was to identify the most appropriate OMs to be translated in clinical practice and clinical trials on DM2. This study has been registered on clinicaltrials.gov NCT03603171 (https://clinicaltrials.gov/ct2/show/NCT03603171). Methods: Sixty-six patients with genetically confirmed DM2 underwent a baseline and a follow-up visit after 1 year. The tested OMs included: hand opening time, pressure pain threshold (PPT), manual muscle testing (MMT), hand held dynamometry (HHD), scale for the assessment and rating of ataxia (SARA), quantitative motor function test (QMFT), gait stairs Gowers chair (GSGC), 30-s sit to stand test, functional index 2 (FI-2) and 6MWT. The PROs included DM1-Active-C, Rasch-built Pompe-specific activity scale (R-Pact), fatigue and daytime sleepiness (FDSS), brief pain inventory short form (BPI-sf), myotonia behavior scale (MBS), and the McGill pain questionnaire. Results: All patients completed the MBS and the results correlated well with the hand-opening time. The PPT showed a low reliability, no correlation with pain questionnaires, and did not differentiate patients with or without myalgia. Both muscle strength assessments, MMT and HHD, showed good construct validity. The QMFT showed an acceptable ceiling effect (14.5%), good convergent and differential validity and performed overall better than GSGC. The SARA score showed high flooring effect and is not useful in DM2. 6MWT proved a valid outcome measure in DM2. The 30-s sit to stand is a feasible test with good convergent validity, showing a flooring effect of 20% as it cannot be used in more severely affected patients. The FI-2 is time-consuming and has a high ceiling effect. At the 1-year visit the only assessments able to detect a worsening of DM2 were HHD, QMFT, and 6MWT, which are the most sensitive to change, and therefore clinically meaningful OMs in DM2. Conclusion: The clinical meaningful motor outcome measures that best depict the multifaceted phenotype of DM2 and its slow progression are MBS, MMT, or HHD (depending on the clinical setting), QMFT, and the 6MWT.
RESUMEN
BACKGROUND: Rhabdomyolysis (RML) is an interdisciplinary condition due to muscle cell injury followed by the release of cell components into circulation. Etiology of RML has a broad range; a serious complication is acute kidney injury (AKI). Despite its high relevance, there is no established formal definition for RML. OBJECTIVES: A systematic review, focusing on RML definition, providing a recommendation for clinicians. METHOD: Systematic literature research in PubMed and Embase (1968-07/2018). RESULTS: The database research presented 8136 articles in PubMed and 2151 in Embase. After screening, 614 papers were retained for statistical analysis. A retrospective study was the most used design (44%). A definition of RML was stated in 231 studies (37.6%), including a precise creatine kinase level (CK) cut-off most frequently (67.1%). In 53/231 (22.9%) studies the CK cut-off was > 5 × upper limit of normal (ULN), and in 64/231 (27.7%) studies > 1000 IU/L. Further components of definitions were elevated CK without specific thresholds, and clinical symptoms. Exclusion criteria referring to the definition of RML were established in 113 studies, including myocardial, renal, cerebral and neuromuscular characteristics. CONCLUSION: At present, we recommend a clinical syndrome of acute muscle weakness, myalgia, and muscle swelling combined with a CK cut-off value of > 1000 IU/L/ or CK > 5 × ULN for the standard definition of a mild RML. Additionally measured myoglobinuria and AKI indicate a severe type of RML. Exclusion criteria as well as the chronological sequence need to be considered for a conclusive RML definition.
Asunto(s)
Lesión Renal Aguda , Creatina Quinasa/sangre , Debilidad Muscular , Mialgia , Rabdomiólisis , Lesión Renal Aguda/fisiopatología , Humanos , Debilidad Muscular/fisiopatología , Mialgia/fisiopatología , Rabdomiólisis/sangre , Rabdomiólisis/diagnóstico , Rabdomiólisis/fisiopatología , Rabdomiólisis/orina , SíndromeRESUMEN
INTRODUCTION: Respiratory complications are relevant in DM1, leading to a significantly increased morbidity and mortality risk in these patients; however, so far only few studies concerning respiratory function have been conducted in DM1 patients. We report a retrospective, multicenter, cross sectional study on a large cohort of DM1 patients widely characterized in the phenotype, to assess prevalence and identify predictors of restrictive respiratory syndrome. METHODS: 268 DM1 subjects aged >18â¯years, who had recently performed spirometric tests were included; restrictive syndrome was diagnosed if forced vital capacity (FVC) <80% of predicted. This cut-off was used for statistical univariate and multivariate analysis. RESULTS: 51.9% patients showed a restrictive syndrome, and half of them had indication to non-invasive ventilation (NIV), yet only 50% resulted compliant to NIV. CTG expansion size in leukocytes, clinical muscle severity, most functional parameters of respiratory muscle involvement, presence of cardiac conduction disturbances, pacemaker (PMK), exertion dyspnea, obstructive sleep apnea, and indication and compliance to NIV were all significantly associated with restrictive syndrome at the univariate analysis; in the multivariate model only the first two factors resulted independent predictors. DISCUSSION: A high prevalence of restrictive syndrome in our DM1 cohort, mainly due to respiratory muscles weakness, was observed and documented; the severity of muscle impairment and the CTG expansion size confirmed to be independent predictors of respiratory restriction. Our data suggest that optimization of respiratory therapeutic management, particularly regarding launching of NIV, might help to reduce the rate of deaths due to respiratory complications in DM1.
Asunto(s)
Distrofia Miotónica/complicaciones , Trastornos Respiratorios/epidemiología , Adulto , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Distrofia Miotónica/fisiopatología , Fenotipo , Prevalencia , Trastornos Respiratorios/etiología , Trastornos Respiratorios/fisiopatología , Estudios Retrospectivos , Espirometría , Capacidad VitalRESUMEN
BACKGROUND: The relative prevalence of myasthenia gravis (MG) subtypes is changing, and their differential features and association with HLA class II alleles are not completely understood. METHODS: Age at onset, presence/absence of autoantibodies (Ab) and thymoma were retrospectively considered in 230 adult Italian patients. Clinical severity, assessed by MGFA scale, and the highest Ab titer were recorded. Furthermore, we performed low/high resolution typing of HLA-DRB1 and HLA-DQB1 alleles to detect associations of these loci with MG subtypes. RESULTS: There were two peaks of incidence: under 41 years of age, with female preponderance, and over 60 years, with higher male prevalence. The former group decreased and the latter increased significantly when comparing onset period 2008-2015 to 2000-2007. Thymomatous (TMG) patients showed a higher prevalence of severe phenotype and significantly higher anti-AChR Ab titer than non-thymomatous (NTMG) patients. Among the latter, those with onset after 60 years of age (LO-NTMG) displayed significantly higher Ab titers but lower MGFA grade compared to early-onset patients (< 41 years; EO-NTMG). Significant associations were found between HLA DQB1*05:01 and TMG patients and between DQB1*05:02 and DRB1*16 alleles and LO-NTMG with anti-AChR Ab. CONCLUSIONS: Two distinct cutoffs (< 41 and > 60 years) conveniently define EO-NTMG and LO-NTMG, with different characteristics. LO-NTMG is the most frequent disease subtype, with an increasing incidence. TMG patients reach higher clinical severity and higher antibody titers than NTMG patients. Moreover, TMG and LO-NTMG with anti-AChR Ab differ in their HLA-DQ association, providing further evidence that these two forms may have different etiologic mechanisms.
Asunto(s)
Miastenia Gravis/epidemiología , Timoma/epidemiología , Neoplasias del Timo/epidemiología , Adulto , Edad de Inicio , Autoanticuerpos/sangre , Femenino , Predisposición Genética a la Enfermedad , Cadenas beta de HLA-DQ/genética , Humanos , Fenómenos Inmunogenéticos , Incidencia , Masculino , Persona de Mediana Edad , Miastenia Gravis/genética , Miastenia Gravis/inmunología , Prevalencia , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Factores Sexuales , Timoma/genética , Timoma/inmunología , Neoplasias del Timo/genética , Neoplasias del Timo/inmunologíaRESUMEN
PURPOSE OF REVIEW: To update current knowledge regarding sleep disturbances and myotonic dystrophies so as to better understand if sleep symptoms may help in the early recognition of the two genetic subtypes: myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2). RECENT FINDINGS: Sleep-disordered breathing (SDB), restless legs syndrome, periodic limb movements in sleep, hypersomnia, and REM sleep dysregulation are frequently described in DM1 patients. SDB does not always explain hypersomnia, but a central dysregulation of sleep-wake modulation is reported mainly in DM1. Sleep apnea, restless legs syndrome, and REM sleep without atonia have been reported in single case reports and small case series of DM2. DM2 is less prevalent and more recently described than DM1, with a milder phenotype than DM1. The most frequent sleep disorders in DM1 are hypersomnia, SDB, periodic limb movements, and a narcoleptic-like phenotype, whereas restless legs syndrome, SDB, and REM sleep without atonia seem to be the most frequent sleep disorders in DM2. Comparative sleep studies are strongly required to delineate the sleep phenotype of myotonic dystrophies.
Asunto(s)
Distrofia Miotónica/complicaciones , Trastornos del Sueño-Vigilia/etiología , Humanos , Distrofia Miotónica/fisiopatología , Síndromes de la Apnea del Sueño/complicaciones , Síndromes de la Apnea del Sueño/fisiopatología , Trastornos del Sueño-Vigilia/fisiopatología , Sueño REM/fisiologíaRESUMEN
We aimed to validate the Nine Hole Peg Test as a measure of dexterity in myotonic dystrophy type 1 (DM1). Fifty patients with adult-onset, genetically confirmed DM1 were evaluated by Nine Hole Peg Test and re-evaluated at one week. Myotonia was not a limiting factor. The first test was compared with that performed by normal subjects (nâ¯=â¯28). Contextually, patients underwent handgrip and three-finger pinch assessments by handheld dynamometer. The Nine Hole Peg Test showed high intra-rater and inter-rater reliability in DM1 [ICC 0.86/0.83 for dominant and 0.90/0.88 for non-dominant hand, respectively]. Inverse correlation with handgrip and pinch strength values (râ¯=â¯-0.4; pâ¯<â¯0.01) and direct correlation with Muscular Impairment Rating Scale (râ¯=â¯0.4; pâ¯<â¯0.01) were found for both DH and NDH. The test was able to differentiate severe DM1 patients, stratified by extent of muscle impairment, from mildly affected and normal controls, with a sensitivity of 97% and 95% for dominant hand and non-dominant hand, respectively (pâ¯<â¯0.0001). In conclusion, we showed that the Nine Hole Peg Test is a reliable, valid and sensitive test of dexterity in DM1, and that it can be considered as a candidate outcome measure to monitor natural history of disease and, possibly, therapeutic response in clinical trials.
Asunto(s)
Fuerza de la Mano/fisiología , Destreza Motora/fisiología , Fuerza Muscular/fisiología , Músculo Esquelético/fisiopatología , Distrofia Miotónica/fisiopatología , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
PURPOSE OF REVIEW: Myotonic dystrophies are the most frequent muscular dystrophies in adulthood; however, myotonic dystrophy type 2 (DM2) is by far less prevalent than myotonic dystrophy type 1 (DM1). Consequently, studies on large cohorts are lacking and disease-specific outcome measures have not been developed (see video abstract, Supplemental Digital Content 1, http://links.lww.com/CONR/A44).The aim of this review is to systematically evaluate the outcome measures applied in patients with DM2 and to identify tests adopted from other neuromuscular disorders potentially suitable for DM2.A systematic review of functional tests and patient reported outcomes (PROs) previously used in DM2 has been performed. In addition, we reviewed functional tests and PROs previously used in neuromuscular diseases (NMDs). Based on this approach, we propose a battery of tests to be validated in DM2. RECENT FINDINGS: No outcome measures or PROs have been validated in DM2. The most used PROs in DM2 were INQoL, SF-36, MPQ, and BPI. It is not clear whether it is better to use MMT or QMT to assess muscle strength. The algometer seems to be a useful tool to assess myalgia. No currently adopted tests or PROs seem effective to assess the mild myotonia of DM2. Several outcome measures used in other NMDs (e.g. 6MWT, QMFT, GSGC) might be suitable for DM2; however, their disease-specific validity needs to be explored. SUMMARY: Although DM2 has a milder and more heterogeneous phenotype than DM1, there is an urgent need to develop validated outcome measures in DM2. The current lack of validated DM2 tests will delay the start of therapeutic trials.
Asunto(s)
Distrofia Miotónica/terapia , Humanos , Reproducibilidad de los Resultados , Resultado del TratamientoRESUMEN
Plexiform neurofibroma is pathognomonic of neurofibromatosis 1 (NF1). An NF1-associated peripheral neuropathy has been described in a small minority of NF1 patients but its histopathological features are poorly characterized. We report the case of a 46-year-old woman presenting with bilateral supraclavicular painful masses without other stigmata of NF1. MRI showed bilateral plexiform lesions extending from cervical roots to the elbows. Nerve conduction studies documented a sensory motor polyneuropathy. Morphometric analysis of sural nerve biopsy showed a preferential loss of large-caliber myelinated fibers with a g ratio of 0.515, and the presence of regeneration clusters. By electron microscopy, marked and diffuse endoneurial fibrosis with an altered relationship between Schwann cells (SC) and collagen fibrils was observed. Moreover both myelinating and non-myelinating SC were characterized by the presence of various cell degradation products. These changes suggest that, in neurofibromatous neuropathy, a widespread axonal atrophy and degeneration take place independently on the presence of tumoral infiltration, possibly due to an impairment in SC-axon cross talk. In this case, the coexistence of plexiform neurofibromas with a peripheral neuropathy strongly suggests a diagnosis of NF1 even without fulfillment of clinical criteria. We propose that in the presence of plexiform neurofibromas, electrophysiological studies should be performed also in asymptomatic patients, in order to detect the existence of a subclinical neuropathy.
Asunto(s)
Neurofibroma Plexiforme/etiología , Neurofibroma Plexiforme/ultraestructura , Neurofibromatosis 1/diagnóstico , Polineuropatías/etiología , Femenino , Humanos , Microscopía Electrónica de Transmisión , Persona de Mediana Edad , Neurofibromatosis 1/complicaciones , Polineuropatías/patologíaRESUMEN
INTRODUCTION: Aquaporins (AQPs) are a family of transmembrane proteins involved in the maintenance of osmotic gradients. AQP4 is abundant in skeletal muscle, where it seems to be associated with glycolytic metabolism. We investigated the pattern of expression of AQP4 in normal human myofibers relative to the main forms of myosin heavy chain (MHC). METHODS: Six normal human muscle biopsies were analyzed by double immunofluorescence for co-expression of AQP4 and slow or fast MHC. RESULTS: A high percentage (64-99%) of MHC-fast positive fibers showed immunoreaction for AQP4. Immunoreactivity for AQP4 was also present in MHC-slow positive fibers, but with a higher variability (5-72%) among biopsies. DISCUSSION: The expression pattern of AQP4 in human myofibers is highly variable among different patients and cannot be predicted for single fibers depending on MHC type expression. Other factors, possibly related to muscle activity, may modulate AQP4 expression. Muscle Nerve 57: 856-859, 2018.
Asunto(s)
Acuaporina 4/metabolismo , Fibras Musculares Esqueléticas/metabolismo , Adolescente , Adulto , Femenino , Antígenos de Histocompatibilidad Clase I/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Cadenas Pesadas de Miosina/metabolismo , Adulto JovenRESUMEN
BACKGROUND: A small number of patients affected by Neutral Lipid Storage Diseases (NLSDs: NLSD type M with Myopathy and NLSD type I with Ichthyosis) have been described in various ethnic groups worldwide. However, relatively little is known about the progression and phenotypic variability of the disease in large specific populations. The aim of our study was to assess the natural history, disability and genotype-phenotype correlations in Italian patients with NLSDs. Twenty-one patients who satisfied the criteria for NLSDs were enrolled in a retrospective cross-sectional study to evaluate the genetic aspects, clinical signs at onset, disability progression and comorbidities associated with this group of diseases. RESULTS: During the clinical follow-up (range: 2-44 years, median: 17.8 years), two patients (9.5%, both with NLSD-I) died of hepatic failure, and a further five (24%) lost their ability to walk or needed help when walking after a mean period of 30.6 years of disease. None of the patients required mechanical ventilation. No patient required a heart transplant, one patient with NLSD-M was implanted with a cardioverter defibrillator for severe arrhythmias. CONCLUSION: The genotype/phenotype correlation analysis in our population showed that the same gene mutations were associated with a varying clinical onset and course. This study highlights peculiar aspects of Italian NLSD patients that differ from those observed in Japanese patients, who were found to be affected by a marked hypertrophic cardiopathy. Owing to the varying phenotypic expression of the same mutations, it is conceivable that some additional genetic or epigenetic factors affect the symptoms and progression in this group of diseases.
Asunto(s)
Eritrodermia Ictiosiforme Congénita/genética , Errores Innatos del Metabolismo Lipídico/genética , Músculo Esquelético/metabolismo , Enfermedades Musculares/genética , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Femenino , Estudios de Asociación Genética , Genotipo , Humanos , Eritrodermia Ictiosiforme Congénita/patología , Italia , Lipasa/genética , Metabolismo de los Lípidos/genética , Errores Innatos del Metabolismo Lipídico/patología , Masculino , Persona de Mediana Edad , Enfermedades Musculares/patología , Mutación/genética , Fenotipo , Respiración Artificial , Estudios Retrospectivos , Adulto JovenRESUMEN
Skin changes have been described in myotonic dystrophy type 1 (DM1). However, whether and in which way skin is a target of specific disease alterations in DM1 and DM2 has not been yet clarified. This study aims to explore cutaneous features of DM1 and DM2 patients. Skin examination was performed in 60 DM1, 15 DM2, and 103 control, unselected patients by means of dermoscopy. It revealed quantitative and qualitative abnormalities of nevi and typical signs of premature aging in both DM1 and DM2 patients, with a significantly higher frequency of dysplastic nevi, alopecia, xerosis and seborrheic dermatitis. Twenty-eight nevi were excised in DM patients and none showed histological features of melanoma, although 12 of them were diagnosed as dysplastic and the remaining 16 presented histological irregularity in melanin distribution. In DM1 patients, the number of nevi correlated with CTG expansion size, whereas the presence of dysplastic nevi and xerosis inversely correlated with vitamin D levels. DM1 and DM2 patients display a high frequency of skin abnormalities, the most common of which correlate with genotype severity and serum vitamin D levels. Skin examination is highly informative in these patients and reveals features suggestive of premature aging and impaired vitamin D homeostasis.
Asunto(s)
Envejecimiento Prematuro/patología , Distrofia Miotónica/sangre , Distrofia Miotónica/patología , Nevo/patología , Neoplasias Cutáneas/patología , Piel/patología , Vitamina D/sangre , Adulto , Anciano , Anciano de 80 o más Años , Homeostasis/fisiología , Humanos , Persona de Mediana Edad , Distrofia Miotónica/complicaciones , Nevo/etiología , Neoplasias Cutáneas/etiología , Adulto JovenRESUMEN
BACKGROUND: Prevalence estimates for the 2 forms of myotonic dystrophy types 1 and 2 (DM1 and DM2) are not exhaustive or non-available. Our aim was to estimate the minimum prevalence of DM1 and DM2 in Italy in the Rome province, applying standards of descriptive epidemiology. METHODS: All patients with a molecular diagnosis of DM1/DM2 and residents in the Rome province in 2013 have been enrolled, and the age-standardized prevalence has been calculated, assuming a Poisson distribution and adjusting for age. RESULTS: We identified 395 DM1 patients: the age-standardized prevalence for total, females and males was 9.65, 8.35 and 11.07/100,000, respectively. The mean age of subjects differed considerably according to CTG repeat length (p = 0.001). Forty DM2 patients were identified. The age-standardized prevalence for total, females and males was 0.99, 1.07 and 0.90/100,000, respectively. The mean age was 57.05. CONCLUSIONS: We estimated for the first time the age-standardized prevalence and the sex and age distribution of DM1 and DM2 in a general population. A higher prevalence of males in DM1 and females in DM2 and a higher mean age of DM2 patients (+8 years) were ascertained. Prevalence of DM2 was 10% that of DM1. These prevalence values are probably lower than mutational rates due to the incomplete penetrance of DM1 mutations and to the clinical elusiveness of DM2. Our findings will be useful in designing cohort studies and for developing a disease registry.
Asunto(s)
Distrofia Miotónica/diagnóstico , Distrofia Miotónica/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Italia/epidemiología , Masculino , Persona de Mediana Edad , Prevalencia , Ciudad de Roma/epidemiología , Distribución por Sexo , Adulto JovenRESUMEN
Recent studies documented an increased risk of neoplasm in patients with myotonic dystrophies (DM). Yet, none of these studies evaluated the contribution of common cancer risk factors in such observation. In this study, we included a cohort of patients (n = 255) with an established molecular diagnosis of DM type 1 (DM1), and who receives their treatment in one of the four centers with recognized expertise in neuromuscular disorders in Rome. We estimated the prevalence of benign and malignant tumors, and assessed if lifestyle factors and/or specific disease features would be associated to their occurrence. Overall, 59 benign tumors in 54 patients and 19 malignant tumors in 17 patients were diagnosed. The most common malignant neoplasms were cancers of the skin (31.6%), thyroid (21.0%), ovary (10.5%), and breast (10.5%). Uterine fibroid was the most common benign tumor (37.6%) in women, while pilomatricoma was the most common in men (28.6%). Age at enrollment (OR = 1.02, 95% CI 1.00-1.05), and female gender (OR = 5.71, 95% CI 2.90-11.22) were associated with tumor development in DM1 patients, while thyroid disorders was associated with malignant tumors only in women (OR = 5.12, 95% CI 1.35-19.37). There was no association between tumor development and evaluated lifestyle factors. In conclusion, the lack of association between common cancer risk factors and tumor development in DM1 support a pathogenic link between tumors and DM1 itself, emphasizing the need for a systematic surveillance. Our observation of an association between thyroid diseases in women and cancer development needs confirmation.
Asunto(s)
Estilo de Vida , Distrofia Miotónica/epidemiología , Distrofia Miotónica/psicología , Neoplasias/epidemiología , Neoplasias/psicología , Adolescente , Adulto , Distribución por Edad , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/clasificación , Factores de Riesgo , Estadísticas no Paramétricas , Adulto JovenRESUMEN
INTRODUCTION: Neutral lipid-storage disease with myopathy is caused by mutations in PNPLA2, which produce skeletal and cardiac myopathy. We report a man with multiorgan neutral lipid storage and unusual multisystem clinical involvement, including cognitive impairment. METHODS: Quantitative brain MRI with voxel-based morphometry and extended neuropsychological assessment were performed. In parallel, the coding sequences and intron/exon boundaries of the PNPLA2 gene were screened by direct sequencing. RESULTS: Neuropsychological assessment revealed global cognitive impairment, and brain MRI showed reduced gray matter volume in the temporal lobes. Molecular characterization revealed a novel homozygous mutation in exon 5 of PNPLA2 (c.714C>A), resulting in a premature stop codon (p.Cys238*). CONCLUSIONS: Some PNPLA2 mutations, such as the one described here, may present with an extended phenotype, including brain involvement. In these cases, complete neuropsychological testing, combined with quantitative brain MRI, may help to characterize and quantify cognitive impairment.
Asunto(s)
Lipasa/genética , Errores Innatos del Metabolismo Lipídico/diagnóstico , Errores Innatos del Metabolismo Lipídico/genética , Enfermedades Musculares/diagnóstico , Enfermedades Musculares/genética , Mutación/genética , Fenotipo , Adulto , Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/genética , Trastornos del Conocimiento/psicología , Humanos , Errores Innatos del Metabolismo Lipídico/psicología , Masculino , Enfermedades Musculares/psicologíaRESUMEN
Myotonic dystrophy type 1 (DM1) is a multisystemic disorder affecting, among others, the endocrine system, with derangement of steroid hormones functions. Vitamin D is a steroid recognized for its role in calcium homeostasis. In addition, vitamin D influences muscle metabolism by genomic and non-genomic actions, including stimulation of the insulin-like-growth-factor 1 (IGF1), a major regulator of muscle trophism. To verify the presence of vitamin D deficit in DM1 and its possible consequences, serum 25-hydroxyvitamin D (25(OH)D), calcium, parathormone (PTH), and IGF1 levels were measured in 32 DM1 patients and in 32 age-matched controls. Bone mineral density (BMD) and proximal muscle strength were also measured by DXA and a handheld dynamometer, respectively. In DM1 patients, 25(OH)D levels were reduced compared to controls, and a significant decrease of IGF1 was also found. 25(OH)D levels inversely correlated with CTG expansion size, while IGF1 levels and muscle strength directly correlated with levels of 25(OH)D lower than 20 and 10 ng/ml, respectively. A significantly higher percentage of DM1 patients presented hyperparathyroidism as compared to controls. Calcium levels and BMD were comparable between the two groups. Oral administration of cholecalciferol in 11 DM1 patients with severe vitamin D deficiency induced a normal increase of circulating 25(OH)D, ruling out defects in intestinal absorption or hepatic hydroxylation. DM1 patients show a reduction of circulating 25(OH)D, which correlates with genotype and may influence IGF1 levels and proximal muscle strength. Oral supplementation with vitamin D should be considered in DM1 and might mitigate muscle weakness.