Parent-reported multi-national study of the impact of congenital and childhood onset myotonic dystrophy

Aim: The frequency and impact of symptoms experienced by patients with congenital, childhood, and juvenile-onset myotonic dystrophy (CDM/ChDM/JDM) is not documented. This report identifies symptomatic areas with the greatest disease burden in an international population of patients with early-onset myotonic dystrophy type-1 (DM1). Method: We distributed surveys to parents of patients with CDM/ChDM/JDM. Patients with CDM/ChDM/JDM were members of the US National Registry of DM1 Patients and Family Members, the Canadian Neuromuscular Disease Registry, or the Swedish Health System. Surveys inquired about 325 symptoms and 20 themes associated with CDM/ChDM/JDM. Parents identified the importance of each symptom and theme to their affected child. The prevalence of each symptom and theme were compared across subgroups of patients. The statistical analysis was performed using Fisher\u27s exact and Kruskal–Wallis tests. Results: One hundred and fifty parents returned surveys. The most frequently reported symptomatic themes in children were issues involving communication (81.7%) and problems with hands or fingers (79.6%). Problems with communication and fatigue were the issues that were reported to have the greatest impact on childrens’ lives, while 24.1% of children reported cardiac disorders and 15.8% had problems with anesthesia. Interpretation: A range of symptoms contribute to the burden of disease faced by children with DM1. Many of these symptoms are under-recognized

Disease Burden and Functional Outcomes in Congenital Myotonic Dystrophy: A Cross-Sectional Study

OBJECTIVE: Herein, we describe the disease burden and age-related changes of congenital-onset myotonic dystrophy (CDM) in childhood. METHODS: Children with CDM and age-matched controls aged 0 to 13 years were enrolled. Participants were divided into cohorts based on the following age groups: 0-2, 3-6, and 7-13 years. Each cohort received age-appropriate evaluations including functional testing, oral facial strength testing, neuropsychological testing, quality-of-life measurements, and ECG. Independent-samples t test or Wilcoxon 2-sample test was used to compare the differences between children with CDM and controls. Probability values less than 0.05 are reported as significant. RESULTS: Forty-one participants with CDM and 29 healthy controls were enrolled. The 6-minute walk was significantly different between CDM (258.3 m [SD 176.0]) and control participants (568.2 m [SD 73.2]). The mean lip force strength was significantly different in CDM (2.1 N [SD 2.8)] compared to control participants (17.8 N [SD 7.6]). In participants with CDM, the mean IQ (65.8; SD 18.4) was 3 SDs below the mean compared to standardized norms. Measurements of grip strength, sleep quality, and quality of life were also significantly different. Strength measures (oral facial strength, grip strength, and 6-minute walk) correlated with each other but not with participant IQ. CONCLUSIONS: This work identifies important phenotypes associated with CDM during childhood. Several measures of strength and function were significantly different between participants with CDM and controls and may be useful during future therapeutic trials

Multiyear monitoring (2007-2013) of flat-tailed horned lizards (Phrynosoma mcallii)

Monitoring programs for species of conservation concern are notoriously flawed. Notably, many monitoring programs do not establish trigger points or a level of decline in population size that will result in management action. Here we report on the monitoring program for the Flat-tailed Horned Lizard (Phrynosoma mcallii) that has been established across its range throughout the United States by the Flat-tailed Horned Lizard Interagency Coordinating Committee (FTHL ICC). Impor- tantly, we examine whether a trigger point of 30% decline was detected in these populations. Between 2007 and 2013, we detected 955 P. mcallii on 2,714 occupancy surveys and captured 715 individuals on 1,861 demographic surveys. Occupancy surveys have demonstrated that the species occurs through- out the management areas and occupancy estimates range from 0.25–0.89. Demographic surveys have demonstrated that population trends over time are correlated across all management areas; however, they are probably driven by factors at smaller geographic scales. During the study no population decline \u3e 30% was detected after accounting for natural and stochastic fluctuations. Continued mon- itoring is called for to gain a greater understanding of what is driving the trends in populations both range-wide and at the scale of management areas

Consensus-based care recommendations for adults with myotonic dystrophy type 1

Purpose of review Myotonic dystrophy type 1 (DM1) is a severe, progressive genetic disease that affects between 1 in 3,000 and 8,000 individuals globally. No evidence-based guideline exists to inform the care of these patients, and most do not have access to multidisciplinary care centers staffed by experienced professionals, creating a clinical care deficit. Recent findings The Myotonic Dystrophy Foundation (MDF) recruited 66 international clinicians experienced in DM1 patient care to develop consensus-based care recommendations. MDF created a 2-step methodology for the project using elements of the Single Text Procedure and the Nominal Group Technique. The process generated a 4-page Quick Reference Guide and a comprehensive, 55-page document that provides clinical care recommendations for 19 discrete body systems and/or care considerations. Summary The resulting recommendations are intended to help standardize and elevate care for this patient population and reduce variability in clinical trial and study environments. Described as “one of the more variable diseases found in medicine,” myotonic dystrophy type 1 (DM1) is an autosomal dominant, triplet-repeat expansion disorder that affects somewhere between 1:3,000 and 1:8,000 individuals worldwide.1 There is a modest association between increased repeat expansion and disease severity, as evidenced by the average age of onset and overall morbidity of the condition. An expansion of over 35 repeats typically indicates an unstable and expanding mutation. An expansion of 50 repeats or higher is consistent with a diagnosis of DM1. DM1 is a multisystem and heterogeneous disease characterized by distal weakness, atrophy, and myotonia, as well as symptoms in the heart, brain, gastrointestinal tract, endocrine, and respiratory systems. Symptoms may occur at any age. The severity of the condition varies widely among affected individuals, even among members of the same family. Comprehensive evidence-based guidelines do not currently exist to guide the treatment of DM1 patients. As a result, the international patient community reports varied levels of care and care quality, and difficulty accessing care adequate to manage their symptoms, unless they have access to multidisciplinary neuromuscular clinics. Consensus-based care recommendations can help standardize and improve the quality of care received by DM1 patients and assist clinicians who may not be familiar with the significant variability, range of symptoms, and severity of the disease. Care recommendations can also improve the landscape for clinical trial success by eliminating some of the inconsistencies in patient care to allow more accurate understanding of the benefit of potential therapies

Quality-of-Life in Charcot-Marie-Tooth Disease: The Patient\u27s Perspective

This study determines the impact of symptoms associated with Charcot-Marie-Tooth disease on quality-of-life. Charcot-Marie-Tooth patients in the Inherited Neuropathies Consortium Rare Diseases Clinical Research Network Contact Registry were surveyed. The survey inquired about 214 symptoms and 20 themes previously identified as important to Charcot-Marie-Tooth patients through patient interviews. Symptom population impact was calculated as the prevalence multiplied by the relative importance of each symptom identified. Prevalence and symptom impact were analyzed by age, symptom duration, gender, Charcot-Marie-Tooth type, and employment status. 407 participants returned the survey, identifying foot and ankle weakness (99.7%) and impaired balance (98.6%) as the most prevalent themes. Foot and ankle weakness and limitations with mobility were the themes with the highest impact. Both symptom prevalence and impact gradually increased with age and symptom duration. Several themes were more prevalent in women with Charcot-Marie-Tooth, including activity limitations, pain, fatigue, hip-thigh weakness, and gastrointestinal issues. All of the themes, except emotional or body image issues, were more prevalent among unemployed individuals. There were minimal differences in symptom prevalence between Charcot-Marie-Tooth types. There are multiple symptoms that impact Charcot-Marie-Tooth quality-of-life in adults. These symptoms have different levels of importance, are readily recognized by patients, and represent critical areas of Charcot-Marie-Tooth health

Factors affecting opening and filling pressures in the lungs of the lizard Pogona vitticeps

Wood, Philip G. ; Daniels, Christopher B

Patient reported quality of life in limb girdle muscular dystrophy

This study determined the frequency and impact of symptoms on quality of life in patients diagnosed with limb girdle muscular dystrophy (LGMD). Participants with a diagnosis of LGMD in registries based at the Coalition to Cure Calpain-3, the Jain foundation, and the Global FKRP Registry competed a survey to report the frequency and relative impact of themes and symptoms of LGMD. Frequency, mean impact, and population impact scores were calculated, and responses were categorized by age, symptom duration, gender, employment status, use of assistive devices, and LGMD subtypes. 134 participants completed the survey. The most prevalent themes included an inability to do activities (100%), limitation with mobility (99.3%), and lower extremity weakness (97.0%). Themes with the greatest impact were: limitations with mobility, lower extremity weakness, and an inability to do activities. Symptom duration and the use of assistive devices were associated with the presence of multiple themes. Employment was associated with the impact of several themes with no differences in frequency. The prevalence and impact of these themes vary in the LMGD population. The most prevalent and impactful themes were related to weakness, but additional concerns related to emotional challenges should also be considered in clinical and research settings

Patient-reported study of the impact of pediatric-onset myotonic dystrophy.

INTRODUCTION: The prevalence and impact of symptoms affecting individuals with pediatric forms of myotonic dystrophy type-1 (DM1) are not well understood. METHODS: Patients from the United States, Canada, and Sweden completed a survey that investigated 20 themes associated with pediatric-onset DM1. Participants reported the prevalence and importance of each theme affecting their lives. Surveys from participants were matched with surveys from their caregivers for additional analysis. RESULTS: The most prevalent symptomatic themes included problems with hands or fingers (79%) and gastrointestinal issues (75%). Problems with urinary/bowel control and gastrointestinal issues were reported to have the greatest impact on patients\u27 lives. Responses from participants and their caregivers had varying levels of agreement among symptomatic themes. DISCUSSION: Many symptoms have meaningful impact on disease burden. The highest levels of agreement between caregivers and individuals with pediatric forms of myotonic dystrophy were found for physical activity themes