Frequency and type of cancers in myotonic dystrophy: A retrospective cross-sectional study.

INTRODUCTION/AIMS: Myotonic dystrophies (DMs) are autosomal dominant diseases in which expression of a mutant expanded repeat mRNA leads to abnormal splicing of downstream effector genes thought to be responsible for their multisystem involvement. Cancer risk and cancer-related deaths are increased in DM patients relative to the general population. We aimed at determining the frequency and type of cancers in both DM1 and DM2 vs a non-DM muscular dystrophy cohort. METHODS: A retrospective, cross-sectional study was carried out on patients with genetically confirmed DM1, DM2, facioscapulohumeral muscular dystrophy (FSHD), and oculopharyngeal muscular dystrophy (OPMD) at our institutions from 2000 to 2020. RESULTS: One hundred eighty-five DM1, 67 DM2, 187 FSHD, and 109 OPMD patients were included. Relative to non-DM, DM patients had an increased cancer risk that was independent of age and sex. Specifically, an increased risk of sex-related (ovarian) and non-sex-related (non-melanoma skin, urological, and hematological) cancers was observed in DM1 and DM2, respectively. The length of CTG repeat expansion was not associated with cancer occurrence in the DM1 group. DISCUSSION: In addition to current consensus-based care recommendations, our findings prompt consideration of screening for skin, urological, and hematological cancers in DM2 patients, and screening of ovarian malignancies in DM1 female patients.

The current status of medical care for myotonic dystrophy type 1 in the national registry of Japan.

INTRODUCTION/AIMS: Myotonic dystrophy (DM) is a systemic disease with multiple organ complications, making the standardization of medical care a challenge. We analyzed data from Japan's national registry to clarify the current treatment patterns and demographic features of Japanese DM patients. METHODS: Using the Japanese National Registry of Muscular Dystrophy (Remudy), we analyzed medical care practice for the multisystemic issues associated with adult DM type 1 patients, excluding congenital DM. RESULTS: We included 809 patients with a median age of 44.2 years. Among these patients, 15.8% used ventilators; 31.7% met the index considered at risk for sudden death due to cardiac conduction defects (PR interval over 240 milliseconds or QRS duration over 120 milliseconds) and 2.8% had implanted cardiac devices. Medication for heart failure was prescribed to 9.6% of patients. Overall, 21.2% of patients had abnormal glucose metabolism, of whom 42.9% were treated with oral medications. Among the oral medications, dipeptidyl peptidase-4 inhibitors were the most common. Cancers were observed in 3.7% of the patients, and endometrial and breast cancers were dominant. Mexiletine was prescribed for myotonia in 1.9% of the patients, and only 1% of the patients received medication for daytime sleepiness. DISCUSSION: This study shows difference in treatment patterns for DM1 in Japan compared with other countries, such as lower rates of use of implantable cardiac devices and higher rates of ventilator use. These data may be useful in discussions aimed at standardizing medical care for patients with DM.

Myotonic dystrophy type 1 in the COVID-19 era.

INTRODUCTION: Myotonic dystrophy type 1 (DM1) is the most prevalent muscular dystrophy in adults. People with DM1 might represent a high-risk population for respiratory infections, including COVID-19. Our aim was to evaluate the characteristics of COVID-19 infection and vaccination rate in DM1 patients. METHODS: This cross-sectional cohort study included 89 patients from the Serbian registry for myotonic dystrophies. Mean age at testing was 48.4 ± 10.4 years with 41 (46.1%) male patients. Mean duration of the disease was 24.0 ± 10.3 years. RESULTS: COVID-19 infection was reported by 36 (40.4%) DM1 patients. Around 14% of patients had a more severe form of COVID-19 requiring hospitalization. The severity of COVID-19 was in accordance with the duration of DM1. A severe form of COVID-19 was reported in 20.8% of patients who were not vaccinated against SARS-CoV-2 and in none of the vaccinated ones. The majority of 89 tested patients (66.3%) were vaccinated against SARS-CoV-2. About half of them (54.2%) received three doses and 35.6% two doses of vaccine. Mild adverse events after vaccination were recorded in 20.3% of patients. CONCLUSIONS: The percentage of DM1 patients who suffered from COVID-19 was like in general population, but with more severe forms in DM1, especially in patients with longer DM1 duration. The study indicated an overall favorable safety profile of COVID-19 vaccines among individuals with DM1 and its ability to protect them from severe COVID-19.

Global Prevalence of Myotonic Dystrophy: An Updated Systematic Review and Meta-Analysis.

INTRODUCTION: Myotonic dystrophy (DM), the most common muscular dystrophy in adults, is a group of autosomal inherited neuromuscular disorders characterized by progressive muscle weakness, myotonia, and cardiac conduction abnormalities. Due to the different gene mutations, DM has been subclassified into DM type 1 (DM1) and type 2 (DM2). However, the prevalence studies on DM and its subtypes are insufficient. METHODS: The PubMed (1966-2022), MEDLINE (1950-2022), Web of Science (1864-2022), and Cochrane Library (2022) databases were searched for original research articles published in English. The quality of the included studies was assessed by a checklist adapted from Strengthening the Reporting of Observational studies in Epidemiology. To derive the pooled epidemiological prevalence estimates, a meta-analysis was performed using the random-effects model. Heterogeneity was assessed using the Cochrane Q statistic and the I2 statistic. RESULTS: A total of 17 studies were included in the systematic review and meta-analysis. Of the 17 studies evaluated, 14 studies were considered medium quality, 2 studies were considered high quality, and 1 study was considered low quality. The global prevalence of DM varied widely from 0.37 to 36.29 cases per 100,000. The pooled estimate of the prevalence of DM was 9.99 cases (95% CI: 5.62-15.53) per 100,000. The pooled estimate of the prevalence of DM1 was 9.27 cases (95% CI: 4.73-15.21) per 100,000, ranging from 0.37 to 36.29 cases per 100,000. The pooled estimate of the prevalence of DM2 was 2.29 cases (95% CI: 0.17-6.53) per 100,000, ranging from 0.00 to 24.00 cases per 100,000. CONCLUSION: Our study provided accurate estimates of the prevalence of DM. The high heterogeneity and the lack of high-quality studies highlight the need to conduct higher quality studies on orphan diseases.

Quality of life and subjective symptom impact in Japanese patients with myotonic dystrophy type 1.

BACKGROUND: Although functional impairment in patients with myotonic dystrophy is an important determinant of the quality of life (QoL), patients' subjective evaluation of their symptoms may also affect their QoL. The aim of this study was to investigate the association between subjective symptom impact and the QoL of patients with myotonic dystrophy, after controlling for functional impairment. METHODS: Eligible patients with myotonic dystrophy type 1 (DM1) were recruited from four hospitals in Japan. The subjective symptom impact of four symptoms (muscle weakness, fatigue, pain, and myotonia) and overall QoL were evaluated using the Individualized Neuromuscular Quality of Life (INQoL) questionnaire. Functional impairment was assessed using the modified Rankin Scale. RESULTS: Seventy-seven patients with DM1 were included in this study. Overall QoL was significantly associated with subjective symptom impact of muscular weakness, fatigue, pain, myotonia, swallowing difficulty, and droopy eyelids. In the regression models, disease duration (beta = 0.11) and moderate to severe functional impairment (beta = 0.33) explained a significant part of the overall QoL. Furthermore, muscular weakness, fatigue, and myotonia significantly explained additional variance of the overall QoL (beta = 0.17-0.43). CONCLUSIONS: Subjective symptom impact and functional impairment are independent features influencing the QoL of Japanese patients with DM1.

A Greek National Cross-Sectional Study on Myotonic Dystrophies.

Myotonic Dystrophies (DM, Dystrophia Myotonia) are autosomal dominant inherited myopathies with a high prevalence across different ethnic regions. Despite some differences, mainly due to the pattern of muscle involvement and the age of onset, both forms, DM1 and DM2, share many clinical and genetic similarities. In this study, we retrospectively analyzed the medical record files of 561 Greek patients, 434 with DM1 and 127 with DM2 diagnosed in two large academic centers between 1994-2020. The mean age at onset of symptoms was 26.2 ± 15.3 years in DM1 versus 44.4 ± 17.0 years in DM2 patients, while the delay of diagnosis was 10 and 7 years for DM1 and DM2 patients, respectively. Muscle weakness was the first symptom in both types, while myotonia was more frequent in DM1 patients. Multisystemic involvement was detected in the great majority of patients, with cataracts being one of the most common extramuscular manifestations, even in the early stages of disease expression. In conclusion, the present work, despite some limitations arising from the retrospective collection of data, is the first record of a large number of Greek patients with myotonic dystrophy and emphasizes the need for specialized neuromuscular centers that can provide genetic counseling and a multidisciplinary approach.

New developments in myotonic dystrophies from a multisystemic perspective.

PURPOSE OF REVIEW: The multisystemic involvement of myotonic dystrophies (DMs) intricates disease monitoring, patients' care and trial design. This update of the multifaceted comorbidities observed in DMs aims to assist neurologists in the complex management of patients and to encourage further studies for still under-investigated aspects of the disease. RECENT FINDINGS: We reviewed the most recent studies covering pathogenesis and clinical aspects of extra-muscular involvement in DM1 and DM2. The largest body of evidence regards the cardiac and respiratory features, for which experts' recommendations have been produced. Gastrointestinal symptoms emerge as one of the most prevalent complaints in DMs. The alteration of insulin signaling pathways, involved in gastrointestinal manifestations, carcinogenesis, muscle function, cognitive and endocrinological aspects, gain further relevance in the light of recent evidence of metformin efficacy in DM1. Still, too few studies are performed on large DM2 cohorts, so that current recommendations mainly rely on data gathered in DM1 that cannot be fully translated to DM2. SUMMARY: Extra-muscular manifestations greatly contribute to the overall disease burden. A multidisciplinary approach is the key for the management of patients. Consensus-based recommendations for DM1 and DM2 allow high standards of care but further evidence are needed to implement these recommendations.

Gender effect on cardiac involvement in myotonic dystrophy type 1.

BACKGROUND AND PURPOSE: Cardiac involvement is observed in about 80% of subjects with myotonic dystrophy type 1 (DM1) and is mainly characterized by cardiac conduction and/or rhythm abnormalities (CCRAs), possibly leading to sudden cardiac death (SCD). Our objective was to investigate whether the gender difference may influence the cardiac involvement and SCD in DM1. METHODS: We analyzed prevalence and incidence of cardiological abnormalities in males versus females in 151 consecutive DM1 patients over a 35-year follow-up period. RESULTS: Fifty-five patients, 35 males (62.5%) and 20 females (42.5%), developed some type of CCRA during the follow-up period (mean 7.82 ± 6.21 years). CCRA overall, and specifically cardiac conduction abnormalities (CCAs), were significantly more frequent in males than in females (p = 0.043 and p = 0.031, respectively). CCRAs progressed in 16 males (45.7%) and six females (30%). Twenty-four patients, 14 males (25.0%) and 10 females (21.3%), died during the follow-up. Nine of them, six males (10.7%) and three females (6.4%), had SCD. After correction for Muscular Impairment Rating Scale progression, cytosine thymine-guanine expansion, and follow-up duration, a higher prevalence of CCAs was independently associated with male gender (p = 0.039), but independent association with gender was not detected for CCRAs overall, cardiac rhythm abnormalities, and SCD prevalence, even if prevalence was higher in males than females. CONCLUSIONS: The overall risk of occurrence of CCAs in DM1 is significantly higher in males than females regardless of genetic background and disease severity and progression. Moreover, the data also suggest a similar impact for male gender for CCRAs overall, CCAs, and SCD even if not statistically significant.

Epigenetics of Myotonic Dystrophies: A Minireview.

Myotonic dystrophy type 1 and 2 (DM1 and DM2) are two multisystemic autosomal dominant disorders with clinical and genetic similarities. The prevailing paradigm for DMs is that they are mediated by an in trans toxic RNA mechanism, triggered by untranslated CTG and CCTG repeat expansions in the DMPK and CNBP genes for DM1 and DM2, respectively. Nevertheless, increasing evidences suggest that epigenetics can also play a role in the pathogenesis of both diseases. In this review, we discuss the available information on epigenetic mechanisms that could contribute to the DMs outcome and progression. Changes in DNA cytosine methylation, chromatin remodeling and expression of regulatory noncoding RNAs are described, with the intent of depicting an epigenetic signature of DMs. Epigenetic biomarkers have a strong potential for clinical application since they could be used as targets for therapeutic interventions avoiding changes in DNA sequences. Moreover, understanding their clinical significance may serve as a diagnostic indicator in genetic counselling in order to improve genotype-phenotype correlations in DM patients.

Occlusal traits and longitudinal dental changes in children and adolescents with congenital or childhood onset myotonic dystrophy.

BACKGROUND/OBJECTIVES: This research aimed to study the malocclusions of children and adolescents with myotonic dystrophy type 1 (DM1), in respect to healthy individuals, and trace the occlusal changes that occurred in these individuals during growth. MATERIALS/METHODS: Thirty-six dental casts, from children and adolescents with DM1 living in western and southern Sweden, were compared with a control group of 50 healthy individuals. To identify potential changes in occlusal traits, 26 casts were assessed and followed-up over a median time of 9 years. Independent samples t-tests were used to compare the two groups and their changes over time. Paired samples t-tests tested changes over time within each group (P < 0.05). RESULTS: DM1 patients had a higher prevalence of anterior open bite, posterior crossbite, and Class III malocclusions. When compared to controls, patients presented smaller upper and lower intermolar as well as intercanine widths. In both groups, the individuals revealed longitudinal changes with a decrease in both upper and lower arch lengths and an increase on the palatal vault height. During the follow-up period, the prevalence of malocclusions remained almost the same, only significantly differing regarding the changes that occurred between groups referred to the upper intermolar width, which decreased among DM1 patients. CONCLUSIONS/IMPLICATIONS: In comparison to healthy controls, children and adolescents with DM1 have shown already at an early age a higher prevalence of both anterior open bite and posterior crossbite. These occlusal traits did not change with time apart from the upper narrow intermolar width, which further decreased with time.

Diabetes, metformin and cancer risk in myotonic dystrophy type I.

Myotonic dystrophy type I (DM1) is an autosomal dominant multisystem disorder characterized by myotonia and muscle weakness. Type 2 diabetes (T2D) and cancer have been shown to be part of the DM1 phenotype. Metformin, a well-established agent for the management of T2D, is thought to have cancer-preventive effects in the general population. In our study, we aimed to assess the association between T2D, metformin use and the risk of cancer in DM1 patients. We identified a cohort of 913 DM1 patients and an age-, sex- and clinic-matched cohort of 12,318 DM1-free controls from the UK Clinical Practice Research Datalink, a large primary care records database. We used Cox regression models to assess cancer risk in T2D patients who were metformin users or nonusers compared to patients without T2D. Separate analyses were conducted for DM1 patients and controls. T2D was more prevalent in DM1 than in controls (8% vs. 3%, p < 0.0001). DM1 patients with T2D, compared to those without T2D, were more likely to develop cancer (hazard ratio [HR] = 3.60, 95% confidence interval [CI] = 1.18-10.97; p = 0.02), but not if they were treated with metformin (HR = 0.43, 95% CI = 0.06-3.35; p = 0.42). Among controls, we observed no significant associations between T2D and cancer risk in either users or nonusers of Metformin (HR = 1.28, 95% CI = 0.91-1.79; p = 0.16 and HR = 1.13, 95% CI = 0.72-1.79; p = 0.59, respectively). These results show an association between T2D and cancer risk in DM1 patients and may provide new insights into the possible benefits of Metformin use in DM1.

Prevalence of Left Ventricular Systolic Dysfunction in Myotonic Dystrophy Type 1: A Systematic Review.

Cardiac involvement is recorded in about 80% of patients affected by myotonic dystrophy type 1 (DM1). The prevalence of cardiac conduction abnormalities and arrhythmias has been well described. Data regarding the prevalence of left ventricle systolic dysfunction (LVSD) and heart failure (HF) are still conflicting. The primary objective of this review was to assess the prevalence of LVSD and HF in DM1. The secondary aim was to examine the association of clinical features with LVSD and to detect predisposing and influencing prognosis factors. A systematic search was developed in MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and Web of Science databases to identify original reports between January 1, 2009, and September 30, 2017, assessing the prevalence of LVSD and HF in populations with DM1. Retrospective and prospective cohort studies and case series describing the prevalence of LVSD, as evaluated by echocardiography, and HF in patients with DM1 were included. Case reports, simple reviews, commentaries and editorials were excluded. Seven studies were identified as eligible, of which 1 was a retrospective population-based cohort study, and 6 were retrospective single-center-based cohort studies. Echocardiographic data concerning LV function were available for 647 of the 876 patients with DM1 who were included in the analysis. The prevalence of LVSD in patients with DM1, defined as LVEF < 55%, was 13.8%, 4.5-fold higher than in general population. Patients with DM1 and LVSD were older, were more likely to be male, had longer baseline atrioventricular and intraventricular conduction-time durations, had higher incidences of atrial arrhythmias, and were more likely to have undergone device implantation. Also, symptomatic HF is more prevalent in patients with DM1 despite their limited levels of physical activity. Further studies are needed to evaluate the prevalence of LVSD and HF in patients with DM1 and to investigate electrocardiographic abnormalities and other clinical features associated with this condition.

SERUM cardiac-specific biomarkers and atrial fibrillation in myotonic dystrophy type I.

INTRODUCTION: The aim of the present study was to evaluate the role of high-sensitivity cardiac troponin I, N terminal pro-B-type natriuretic peptide (NT-proBNP), creatine kinase-MB mass concentration (CK-MB mass) and copeptin (CP) in predicting incident atrial fibrillation (AF) in myotonic dystrophy type 1 (DM1) patients. MATERIALS AND METHODS: The study enrolled 60 consecutive DM1 patients (age 50.3 ± 7.3 years, 34 male) who underwent pacemaker (PM) implantation for cardiac rhythm abnormalities and 60 PM recipients whose age and sex matched served as control group. All DM1 patients underwent a 12-lead electrocardiogram, 2D color Doppler echocardiogram, biomarkers measurements and device interrogation at implantation, 1 month after and every 6 months thereafter for a minimum of 2-year follow-up. RESULTS: The study population was divided into two groups according to the presence of AF (AF group vs non-AF group). The AF group was older (47.3 ± 8 vs 38.6 ± 7 years, P = .03) and showed higher serum levels of NT-proBNP (151 ± 38.4 vs 107.3 ± 24.2 pg/mL, P < .001) and CP (18.9 ± 4.5 vs 7 ± 2.3 P < .001) than non-AF Group. NT-proBNP (P < .001) and CP (P < .001) were found to be an independent predictor of AF. Based on the receiver-operating characteristics curve analysis, the cut-off value for NT-proBNP that best predicted AF event in DM1 patients was 123 pg/ml (sensitivity of 83.3% and specificity of 86.5%); the cut-off value for CP that best predicted AF event in DM1 patients was 9 pmol/L (sensitivity of 89% and specificity of 87%). CONCLUSION: NT-proBNP and CP represent two independent predictors of AF onset in DM1 population with conduction disturbances underwent PM implantation.

The myotonic dystrophy experience: a North American cross-sectional study.

INTRODUCTION: Myotonic dystrophy (DM) is a chronic, multisystemic, neurological condition. Patients and caregivers are uniquely suited to identify what symptoms are most important and highlight the unmet needs that are most relevant to DM. METHODS: We conducted a North American, cross-sectional study of people with DM type-1, congenital DM, and DM type-2 and their family members. We sent patients and caregivers separate surveys to identify and quantitate the issues of greatest importance, examine the differences between groups, and identify the most important challenges experienced by this population. RESULTS: 1,180 people with DM and 402 family members/caregivers responded to the surveys. They reported considerable physical and cognitive symptoms, extensive diagnostic delays, and varying clinical phenotypes on the basis of DM type. DISCUSSION: Marked disease burden and numerous unmet needs exist in DM. These needs vary based on DM type and highlight the complex clinical phenotypes of these neurological disorders. Muscle Nerve 59:457-464, 2019.

Survival patterns and cancer determinants in families with myotonic dystrophy type 1.

BACKGROUND AND PURPOSE: Research indicates that patients with myotonic dystrophy type 1 (DM1) are at increased risk of cancer and early death. Family data may provide insights given DM1 phenotypic heterogeneity, the broad range of non-muscular manifestations and the usual delays in the diagnosis of DM1. METHOD: Family history data were collected from 397 genetically and/or clinically confirmed DM1 patients (respondents) enrolled in the US or UK myotonic dystrophy registries. Standardized mortality ratios were calculated for DM1 first-degree relatives (parents, siblings and offspring) by their reported DM1 status (affected, unaffected or unknown). For cancer-related analyses, mixed effects logistic regression models were used to evaluate factors associated with cancer development in DM1 families, including familial clustering. RESULTS: A total of 467 deaths and 337 cancers were reported amongst 1737 first-degree DM1 relatives. Mortality risk amongst relatives reported as DM1-unaffected was comparable to that of the general population [standardized mortality ratio (SMR) 0.82, P = 0.06], whilst significantly higher mortality risks were noted in DM1-affected relatives (SMR = 2.47, P < 0.0001) and in those whose DM1 status was unknown (SMR = 1.60, P < 0.0001). In cancer risk analyses, risk was higher amongst families in which the DM1 respondent had cancer (odds ratio 1.95, P = 0.0001). Unknown DM1 status in the siblings (odds ratio 2.59, P = 0.004) was associated with higher cancer risk. CONCLUSION: There is an increased risk of death, and probably cancer, in relatives with DM1 and in those whose DM1 status is unknown. This suggests a need to perform a careful history and physical examination, supplemented by genetic testing, to identify family members at risk for DM1 and who might benefit from disease-specific clinical care and surveillance.

Myocardial fibrosis by late gadolinium enhancement cardiovascular magnetic resonance in myotonic muscular dystrophy type 1: highly prevalent but not associated with surface conduction abnormality.

BACKGROUND: Conduction disease and arrhythmias represent a major cause of mortality in myotonic muscular dystrophy type 1 (MMD1). Permanent pacemaker (PPM) implantation is the cornerstone of therapy to reduce cardiovascular mortality in MMD1. Cardiovascular magnetic resonance (CMR) studies demonstrate a high prevalence of myocardial fibrosis in MMD1, however the association between CMR myocardial fibrosis with late gadolinium enhancement (CMR-LGE) and surface conduction abnormality is not well established in MMD1. We investigated whether myocardial fibrosis by CMR-LGE is associated with surface conduction abnormalities meeting criteria for PPM implantation according to current guidelines in a cohort of patients with genetically confirmed MMD1. METHODS: Patients with genetically confirmed MMD1 were retrospectively evaluated. 12-lead electrocardiography (ECG) performed within 6 months of CMR was necessary for inclusion. The severity and extent of MMD1 was quantified using a validated Muscular Impairment Rating Scale (MIRS). Based on current guidelines for device-based therapy of cardiac rhythm abnormalities, we defined surface conduction abnormality as the presence of ECG alterations meeting criteria for PPM implant (class I or II indications): PR interval > 200 ms (type I atrioventricular (AV) block) and/or mono or bifascicular block (QRS > 120 ms), or evidence of advanced AV block. Balanced steady-state free precession sequences (bSSFP) were used for assessment of left ventricular (LV) volumes and ejection fraction. MOdified Look-Locker Inversion Recovery (MOLLI) acquisition schemes were used to acquire T1 maps. Patients' charts were reviewed up to 12 months post-CMR for occurrence of PPM implantation. RESULTS: Fifty-two patients (38% male, 41 ± 14 years) were included. Overall, 31 (60%) patients had a surface conduction abnormality and 22 (42%) demonstrated midwall myocardial fibrosis by CMR-LGE. After a median of 57 days from CMR exam, 15 patients (29%) underwent PPM implantation. Subjects with vs. without surface conduction abnormality had significantly longer disease length (15.5 vs. 7.8 years, p = 0.015) and higher disease severity on the MIRS scale (p = 0.041). High prevalence of myocardial fibrosis by CMR-LGE was detected in subjects with and without surface conduction abnormality with no significant difference between the two cohorts (42% vs. 43%, p = 0.999). By multivariate logistic regression analysis, disease length was the only independent variable associated with surface conduction abnormality (OR 1.071, 95%CI 1.003-1.144, p = 0.040); while CMR-LGE was not associated with conduction abnormality (ρ = - 0.009, p = 0.949). CONCLUSIONS: Myocardial fibrosis by CMR-LGE is highly prevalent in MMD1 but not related to surface conduction abnormality meeting current guideline criteria for PPM implantation .

Cognitive and adaptive functioning in congenital and childhood forms of myotonic dystrophy type 1: a longitudinal study.

AIM: To conduct a longitudinal follow-up of the development of global cognitive abilities and adaptive skills in individuals with congenital and childhood forms of myotonic dystrophy type 1 (DM1). METHOD: Fifty-one participants (29 males, 22 females, mean age 19y 5mo, SD 4y 11mo, range 10y 10mo-28y 11mo) were divided into severe congenital (n=16), mild congenital (n=17), and childhood DM1 (n=18) subgroups. The average time between the first and second assessments was 7 years 8 months. Adaptive skills were evaluated using the Vineland Adaptive Behavior Scales and global cognitive functioning using Wechsler scales. RESULTS: There was no statistically significant decline in cognitive abilities and adaptive behaviour. A tendency of decline regarding the level of intellectual disability was found in the congenital DM1 groups but not in the childhood group. In the congenital DM1 groups, the gap in relation to typically developing peers in cognitive and adaptive functioning increased. Predictors of change over time in adaptive skills were age and current level of intellectual disability: individuals with severe intellectual disability and younger individuals deteriorated the most. However, when raw scores were compared, no actual regression in adaptive functioning was found. INTERPRETATION: The participants had not lost any important adaptive skills. Greater cognitive and adaptive development was found in the childhood group than in the congenital groups. WHAT THIS PAPER ADDS: There is no absolute decline in cognitive and adaptive abilities in individuals with congenital and childhood myotonic dystrophy type 1. Pace of development is slow in comparison with normative data. The childhood group tended to show greater cognitive and adaptive development than the congenital groups.

FUNCIONAMIENTO COGNITIVO Y ADAPTATIVO EN LA INFANCIA Y FORMAS CONGÉNITAS DE DISTROFIA MIOTÓNICA TIPO 1: UN ESTUDIO LONGITUDINAL: OBJETIVO: Realizar un seguimiento longitudinal del desarrollo de las capacidades cognitivas globales y las habilidades de adaptación en individuos con formas congénitas e infantiles de distrofia miotónica tipo 1 (DM1). MÉTODO: Cincuenta y un participantes (29 varones, 22 mujeres, edad media 19 y 5 meses, SD 4 años y 11 meses, rango 10 años y 10 meses y 28 años y 11 meses) se dividieron en congénitos graves (n = 16), congénitos leves (n = 17) y DM infantil 1 (n = 18). El tiempo promedio entre la primera y la segunda evaluación fue de 7 años y 8 meses. Las habilidades adaptativas se evaluaron utilizando las escalas de comportamiento adaptativo de Vineland y el funcionamiento cognitivo global utilizando escalas de Wechsler. RESULTADOS: No hubo una disminución estadísticamente significativa en las capacidades cognitivas y el comportamiento adaptativo. Se encontró una tendencia de disminución con respecto al nivel de discapacidad intelectual en los grupos de DM1 congénitos, pero no en el grupo de la infancia. En los grupos de DM1 congénitos, la brecha en relación con los compañeros de desarrollo típico en el funcionamiento cognitivo y adaptativo aumentó. Los factores predictivos del cambio a lo largo del tiempo en las habilidades de adaptación fueron la edad y el nivel actual de discapacidad intelectual: las personas con discapacidad intelectual grave y las personas más jóvenes se deterioraron más. Sin embargo, cuando se compararon las puntuaciones brutas, no se encontró una regresión real en el funcionamiento adaptativo. INTERPRETACIÓN: Los participantes no habían perdido ninguna habilidad adaptativa importante. Se encontró mayor desarrollo cognitivo y adaptativo en el grupo infantil que en los grupos congénitos.

FUNCIONAMENTO COGNITIVO E ADAPTATIVO EM FORMAS CONGÊNITAS INFANTIS DA DISTROFIA MIOTÔNICA TIPO 1: UM ESTUDO LONGITUDINAL: OBJETIVO: Conduzimos um acompanhamento longitudinal do desenvolviemtno de capacidades cognitivas globais e capacidades adaptativas em indivíduos com formas congênitas e da infantis da distrofia miotônica tipo 1 (DM1). MÉTODO: Cinquenta e um participantes (29 do sexo masculino, 22 do sexo feminino, média de idade 19a 5m, DP 4a 11m, variação 10a 10m-28a 11m) foram divididos em DM1 congênita severa (n=16), congênita leve (n=17), e da infância (n=18). O tempo médio entre a primeira e a segunda avaliação foi 7 anos e 8 meses. Capacidades adaptativas foram avaliadas usando as Escalas Vineland de Comportamento Adaptativo, e as escalas Wechsler de funcionamento cognitivo global. RESULTADOS: Não houve declínio estatisticamente significativo nas capacidades cognitivas e comportamento adaptativo. Uma tendência de declínio no nível de incapacidade intelectual foi encontrado nos grupos de DM1congênita, mas não no grupo da infância. Nos grupos com DM1 congênita, a distância em relação aos pares com desenvolvimento típico no funcionamento cognitivo e adaptativo aumentou. Preditores de mudança com o passar do tempo nas habilidades adaptativas foram a idade e o nível atual de incapacidade intelectual: indivíduos com incapacidade intelectual severa e indivíduos mais jovens deterioraram mais. No entanto, quando as pontuações brutas foram comparadas, nenhuma regressão real no funcionamento adaptativo foi encontrada. INTERPRETAÇÃO: Os participantes não perderam nenhuma habilidade adaptativa importante. Maior desenvolvimento cognitivo e adaptativo foi encontrado no grupo da infância comparado aos grupos congênitos.

Body composition analysis in patients with myotonic dystrophy types 1 and 2.

INTRODUCTION: To date, there are only several reports on body composition in myotonic dystrophy type 1 (DM1) and there are no data for myotonic dystrophy type 2 (DM2). The aim was to analyze body composition of patients with DM1 and DM2, and its association with socio-demographic and clinical features of the diseases. METHODS: There were no statistical differences in sociodemographic features between 20 DM1 patients and 12 DM2 patients. Body composition was assessed by DEXA (dual-energy x-ray absorptiometry). A three-compartment model was used: bone mineral content (BMC), fat mass (FM), and lean tissue mass (LTM). RESULTS: Patients with DM1 and DM2 had similar total body mass (TBM), BMC, FM, and LTM. Patients with DM1 had higher trunk-limb fat index (TLFI) in comparison to DM2 patients which indicates visceral fat deposition in DM1 (1.16 ± 0.32 for DM1 vs. 0.87 ± 0.23 for DM2, p < 0.05). Right ribs bone mineral density was lower in DM2 group (0.68 ± 0.07 g/cm2 vs. 0.61 ± 0.09 g/cm2, p < 0.05). Higher percentage of FM in legs showed correlation with lower strength of the upper leg muscles in DM1 (ρ = - 0.47, p < 0.05). Higher muscle strength in DM2 patients was in correlation with higher bone mineral density (ρ = + 0.62, p < 0.05 for upper arm muscles, ρ = + 0.87, p < 0.01 for lower arm muscles, ρ = + 0.72, p < 0.05 for lower leg muscles). CONCLUSION: DM1 patients had visceral obesity, and percentage of FM correlated with a degree of muscle weakness in upper legs. In DM2 patients, degree of muscle weakness was in correlation with higher FM index and lower bone mineral density.

Family communication following a diagnosis of myotonic dystrophy: To tell or not to tell?

Family communication about genetic information enables informed medical and reproductive decision-making. The literature suggests that a significant proportion of genetically at-risk family members remain uninformed about genetic risk information as a result of non-disclosure. This study explored the experiences of New Zealand families communicating about a diagnosis of type 1 myotonic dystrophy (DM1). Eligible individuals were identified and recruited from the New Zealand (NZ) MD Prev study, a nationwide study which aimed to determine the prevalence, impact, and costs of genetic muscle disorders across the lifespan. Twelve qualitative semi-structured interviews were conducted with 17 participants. The findings demonstrate diversity among and within families, with several distinct family narratives described. Most participants reported a motivation to tell relatives about their diagnosis to promote autonomy. Women were pivotal throughout communication processes and this was often tied to the concept of maternal responsibility and a desire to promote relatives' reproductive autonomy. The diagnosis of DM1 and the subsequent family communication decisions altered relationships for many, with both positive and negative impacts described. The findings demonstrate that individuals require time to explore the impact of a diagnosis of DM1 on self, family and intimate partner relationships to anticipate unique communication challenges. Genetic counselors can use these findings to inform their approach to counseling families with DM1. Longitudinal genetic counseling may be beneficial as a way to provide individuals with life stage specific support as they communicate with their relatives about a diagnosis of DM1.

Risk of skin cancer among patients with myotonic dystrophy type 1 based on primary care physician data from the U.K. Clinical Practice Research Datalink.

Myotonic dystrophy type 1 (DM1) is an inherited multisystem neuromuscular disorder caused by a CTG trinucleotide repeat expansion in the DMPK gene. Recent evidence documents that DM1 patients have an increased risk of certain cancers, but whether skin cancer risks are elevated is unclear. Using the U.K. Clinical Practice Research Datalink (CPRD), we identified 1,061 DM1 patients and 15,119 DM1-free individuals matched on gender, birth year (±2 years), attending practice and registration year (±1 year). We calculated the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association of DM1 diagnosis with skin cancer risk using Cox proportional hazards models, for all skin cancers combined and by histological subtype. Follow-up started at the latest of the age at practice registration, DM1 diagnosis/control selection or January 1st 1988, and ended at the earliest of the age at first skin cancer diagnosis, death, transfer out of the practice, last date of data collection or the end of the CPRD record (October 31, 2016). During a median follow-up of 3.6 years, 35 DM1 patients and 108 matched DM1-free individuals developed a skin cancer. DM1 patients had an increased risk of skin cancer overall (HR = 5.44, 95% CI = 3.33-8.89, p < 0.0001), and basal cell carcinoma (BCC) (HR = 5.78, 95% CI = 3.36-9.92, p < 0.0001). Risks did not differ by gender, or age at DM1 diagnosis (p-heterogeneity > 0.5). Our data confirm suggested associations between DM1 and skin neoplasms with the highest risk seen for BCC. Patients are advised to minimize ultraviolet light exposure and seek medical advice for suspicious lesions.