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Background: To attain the most comprehensive view of the quality of life (QoL) of a child with Duchenne Muscular Dystrophy (DMD), the completion of a pediatric QoL measure by the child and his/her parent and the assessment of QoL and health-related quality of life (HRQoL) as separate constructs is crucial. Previous QoL research has not assessed HRQoL as a separate construct. By using the Quality of My Life (QoML) questionnaire, our objective was to describe QoL and HRQoL in boys with DMD based on child-and parent-reports. Methods: Parent and child dyads identified via the Canadian Neuromuscular Disease Registry received QoML questionnaires (2013-2016). Children and parent-proxy each completed the QoL and HRQoL Visual Analog Scales. Responses were marked on a 10-cm line, with higher scores (max=10) reflecting higher QoL and HRQoL. Descriptive statistics were computed for child- and parent-reports of QoL and HRQoL at three time-points. Results: Mean(SD) QoL and HRQoL scores for child- and parent-reports were: 1) Baseline (n=20 dyads), 8.32(1.72) vs. 6.73(2.23) and 7.63(2.51) vs. 6.73(2.19); 2)18-months (n=10 dyads, n=9 dyads), 7.83(2.05) vs 7.66(1.66) and 7.62(2.41) vs 7.41(2.16); 3) 36-months (n=15 dyads) 7.38(2.00) vs. 6.99(1.77) and 7.19(2.70) vs. 6.76(2.26). Conclusions: Boys with DMD report higher QoL and HRQoL compared to their parents.
Background: SMA is characterized by reduced levels of survival of motor neuron (SMN) protein from deletions and/or mutations of the SMN1 gene. While SMN1 produces full-length SMN protein, a second gene, SMN2, produces low levels of functional SMN protein. Risdiplam (RG7916/RO7034067) is an investigational, orally administered, centrally and peripherally distributed small molecule that modulates pre-mRNA splicing of SMN2 to increase SMN protein levels. Methods: SUNFISH (NCT02908685) is an ongoing multicenter, double-blind, placebo-controlled, operationally seamless study (randomized 2:1, risdiplam:placebo) in patients aged 2–25 years, with Type 2/3 SMA. Part 1 (n=51) assesses safety, tolerability, pharmacokinetics and pharmacodynamics of different risdiplam dose levels. Pivotal Part 2 (n=180) assesses safety and efficacy of the risdiplam dose level selected based on Part 1 results. Results: Part 1 results showed a sustained, >2-fold increase in median SMN protein versus baseline following 1 year of treatment. Adverse events were mostly mild, resolved despite ongoing treatment and reflected underlying disease. No drug-related safety findings have led to withdrawal (data-cut 06/17/18). SUNFISH Part 1 exploratory endpoint results and Part 2 study design will also be presented. Conclusions: To date, no drug-related safety findings have led to withdrawal. Risdiplam led to sustained increases in SMN protein levels.
Oats can be processed in a variety of ways ranging from minimally processed such as steel-cut oats (SCO), to mildly processed such as large-flake oats (old fashioned oats, OFO), moderately processed such as instant oats (IO) or highly processed in ready-to-eat oat cereals such as Honey Nut Cheerios (HNC). Although processing is believed to increase glycaemic and insulinaemic responses, the effect of oat processing in these respects is unclear. Thus, we compared the glycaemic and insulinaemic responses elicited by 628 kJ portions of SCO, OFO, IO and HNC and a portion of Cream of Rice cereal (CR) containing the same amount of available-carbohydrate (23 g) as the oatmeals. Healthy males (n 18) and females (n 12) completed this randomised, cross-over trial. Blood was taken fasting and at intervals for 3 h following test-meal consumption. Glucose and insulin peak-rises and incremental AUC (iAUC) were subjected to repeated-measures ANOVA using Tukey’s test (two-sided P<0·05) to compare individual means. Glucose peak-rise (primary endpoint, mean (sem) mmol/l) after OFO, 2·19 (sem 0·11), was significantly less than after CR, 2·61 (sem 0·13); and glucose peak-rise after SCO, 1·93 (sem 0·13), was significantly less than after CR, HNC, 2·49 (sem 0·13) and IO 2·47 (sem 0·13). Glucose iAUC was significantly lower after SCO than CR and HNC. Insulin peak rise was similar among the test meals, but insulin iAUC was significantly less after SCO than IO. Thus, the results show that oat processing affects glycaemic and insulinaemic responses with lower responses associated with less processing.
Introduction: Patients with advanced or end-stage illness frequently present to emergency departments (EDs), many of whom are in need of palliative care (PC). Emergency physicians have struggled in providing high quality care to these patients and there is a need to identify cost-effective PC interventions delivered in the ED to improve patient outcomes. The objective of this systematic review was to examine the effectiveness of ED-based PC interventions. Methods: A comprehensive search of nine electronic databases and grey literature sources was conducted to identify any comparative studies assessing the effectiveness of ED-based PC interventions to improve health outcomes of patients with advanced or end-stage illness. Two independent reviewers completed study selection, quality assessment, and data extraction. Differences were mediated via third-party adjudication. Relative risks (RR) with 95% confidence intervals (CIs) were calculated using a random effects model and heterogeneity (I2) was reported. Results: From 5882 potentially eligible citations, 12 studies were included. Two studies are currently on-going clinical trials, and as such, 10 studies were included in this analysis. The studies consisted of before-after studies (n = 5), RCTs (n = 4), and an observational cohort (n = 1). Interventions assessed among the included studies consisted primarily of ED-directed PC consultations (n = 6), while other studies assessed screening of patients with advanced or end-stage illness and PC needs (n = 2), education on PC for ED-staff (n = 1), and an ED-based critical care unit (n = 1). Infrequent reporting of important outcomes (e.g., Mortality, ED relapse) limited the ability of this review to conduct meaningful meta-analysis. There was no difference in patient mortality between two studies assessing ED-directed PC consultations (RR = 0.89; 95% CI: 0.71, 1.13; I2 = 0%). One before-after study (RR = 0.73; 95% CI: 0.47, 1.13) and two RCTs (RR = 2.19; 95% CI: 0.40, 11.92; I2 = 96%) did not identify significant differences in PC consultations intervention (implementation of ED-directed PC consultations) and control (usual care) patients. Conclusion: This review found limited evidence to support the recommendation of any particular ED-based intervention for patients presenting to the ED with advanced or end-stage illness. High quality studies and standardized outcome reporting are needed to better understand the impact of PC interventions in the ED setting.
Introduction: Acute migraine headaches are common causes of presentation to the emergency department (ED). There is great variability in the efficacy of the available parenteral agents to manage pain, though triptans are among the recommended treatments. The objective of this systematic review was to update a previous review examining the effectiveness of parenteral agents for the treatment of acute migraine in the ED or equivalent acute care setting; our review examined pain management in emergency settings and assessed the effectiveness of triptan agents. Methods: A comprehensive search of 10 electronic databases and grey literature was conducted to supplement the previous systematic review. Two independent reviewers completed study selection, quality assessment, and data extraction. Any discrepancies were resolved by third party adjudication. Pain scale scores were analyzed using standardized mean difference (SMD) with 95% confidence intervals (CIs) calculated using a random effects model; heterogeneity (I2) was reported. Results: Titles and abstracts of 5039 unique studies were reviewed, of which, 51 studies were included. Sixty-four studies from the original review were included, resulting in a total of 115 included studies. Pain was measured within the ED or equivalent acute care setting using a variety of pain scales, most commonly the 0-10 cm or 100 mm visual analog scale. Four studies compared pain scores between patients receiving sumatriptan vs. other agents, of which, patients receiving sumatriptan reported higher pain scale scores (SMD = 0.53; 95% CI: 0.04, 1.02; I2 = 80%). In particular, patients receiving sumatriptan reported higher pain scale scores than patients receiving metoclopramide (SMD = 0.68; 95% CI: 0.31, 1.04; n = 1) or ketorolac (SMD = 1.39; 95% CI: 0.56, 2.21; n = 1). Overall, studies comparing anti-inflammatory agents (i.e., ketorolac or dexketoprofen) to other agents reported improved pain scale scores among patients receiving anti-inflammatory agents (SMD = -0.38; 95% CI: -0.73, -0.03; I2 = 66%; n = 5). Conclusion: Limited evidence suggests that patients treated with metoclopramide or anti-inflammatory agents experience greater pain reduction compared to patients treated with sumatriptan. This review will conduct a network analysis of parenteral agents to examine the comparative effectiveness of parenteral agents to manage pain among patients with acute migraine. Further analysis will also consider the balance between efficacy and adverse events.
Introduction: With an increasing proportion of patients in need of end-of-life (EOL) care presenting to the emergency department (ED), many of these patients may benefit from early palliative care (PC) referral. In fact, early PC referral is one of the Choosing Wisely ED recommendations in the USA. As such, there is a potential benefit to identifying patients with advanced or end-stage illness with PC needs. The objective of this systematic review is to identify and synthesize the available evidence regarding the existence and psychometric properties of screening tools to identify patients with advanced or end-stage illness and PC needs presenting to EDs. Methods: A comprehensive search of eight electronic databases and the grey literature was conducted. Studies assessing the ability of a screening instrument to identify ED patients with advanced or end-stage illness in need of PC were eligible for inclusion. Two independent reviewers completed study selection, quality assessment, and data extraction. Disagreements were resolved through third-party adjudication. Due to the significant heterogeneity, as well as inconsistent outcome reporting, a descriptive summary of the results was completed. Results: Once duplicates were removed, the title and abstracts of 3516 studies were screened, of which, 15 studies were included. Overall, 10 unique screening instruments were assessed across the studies. The most commonly assessed screening tool was the use of the modified surprise question (SQ), in which physicians were asked if they would be surprised if the patient died within a specified period of time. Only four of the included studies assessed the diagnostic or psychometric properties of the screening tools. One study reported that the modified SQ predicted PC consultation with 35% sensitivity, 89% specificity, and a negative predictive value of 97%. The proportion of patients identified with PC needs ranged from 12% to 73%, with studies utilizing the SQ reporting a range of 12% to 33%. Conclusion: A variety of screening tools are available to identify ED patients with advanced or end-stage illness who would benefit from a referral for PC. While the modified SQ was the most common instrument assessed and appears to be simple to implement, it is unclear if the diagnostic and psychometric properties of this tool are sufficiently robust to warrant widespread implementation.
Introduction: Although a variety of parenteral agents exist for the treatment of acute migraine, relapse after an emergency department (ED) visit is still a common occurrence. The objective of this systematic review was to update a previous review examining the effectiveness of parenteral agents for the treatment of acute migraine in the ED or equivalent acute care setting; our review focused on those studies aiming a reduction in relapse after an ED visit. Methods: A comprehensive search of 10 electronic databases and grey literature was conducted to identify comparative studies to supplement the previous systematic review. Two independent reviewers completed study selection, quality assessment, and data extraction. Any discrepancies were resolved by third party adjudication. Relative risks (RR) with 95% confidence intervals (CIs) were calculated using a random effects model and heterogeneity (I2) was reported. Results: Titles and abstracts of 5039 unique studies were reviewed, of which, 51 studies were included. Sixty-four studies from the original review were included, resulting in a total of 115 included studies. Relapse was reported in 44 (38%) included studies and occurred commonly in patients receiving placebo or no interventions (median = 39%; IQR: 14%, 47%). Overall, no differences in headache relapse were found between patients receiving sumatriptan or placebo (RR = 1.09; 95% CI: 0.55, 2.17; I2 = 93%; n = 8). Conversely, patients receiving neuroleptic agents experienced fewer relapses compared to placebo (RR = 0.27; 95% CI: 0.12, 0.58; I2 = 0%; n = 3); however, patients receiving neuroleptics reported an increase in adverse events (RR = 1.87; 95% CI: 1.17, 3.00; I2 = 0%; n = 3). Compared to placebo, patients receiving dexamethasone were less likely to experience a headache recurrence (RR = 0.71; 95% CI: 0.53, 0.95; I2 = 60%, n = 9); however, no differences were found in reported adverse events (RR = 1.09; 95% CI: 0.81, 1.47; I2 = 0%; n = 3). Conclusion: Relapse is a common occurrence for patients with migraine headaches. This review found patients receiving neuroleptics or dexamethasone experienced fewer headache recurrences. Conversely, triptan agents appear to have minimal effect on reducing the risk for headache recurrence following discharge from an acute care setting. Limited available data on adverse events is an important limitation to inform decision-making. Guidelines should be revised to reflect these results.
Introduction: While boarding of patients in the emergency department (ED) has been well documented and is carefully monitored, the time spent in emergency beds by patients waiting for Adult Protection (AP) placement is often relatively unnoticed, as they are not flagged as ‘admitted’. These patients have no emergency needs, yet consume considerable ED resources, often in excess of patients requiring emergency care. Staff familiarity with this issue may also bias them to premature diagnostic closure of patients as ‘placement problems’, risking misdiagnosis of active medical conditions. An observational study to retrospectively quantify the time spent in the ED by patients referred to AP services for urgent placement from the ED. Methods: A three-year audit of ED social work records of patients referred for AP. Results: For the period of October 1 2015-September 30, 2018, the ED social work service kept records of patients referred for AP from the ED. During this period, a total of 142 patients were referred to AP (40, 50, and 52 in each year respectively). There was an increase of 10 patients between 2015/16 and 2016/17 and two patients from 2016/17 to 2017/18. The overall length of stay for this subset of ED patients during this three-year period was alarmingly high, with an average length of stay of four days per patient (range 2.7 hours-18.5 days) compared to an average of all patients of 4.9 hours and admitted patients of 13.6 hours. Conclusion: Patients in the ED who are referred to AP services consume considerable ED resources, often requiring complete medical work-up, capacity assessments and close monitoring by multiple emergency personnel. This has been reported to cause considerable stress and friction between staff and consulting services. Furthermore, these patients are poorly served in a hectic, brightly lit, and noisy environment. The impact is often not fully appreciated due to ineffective capture by patient tracking systems.
Whereas genetic susceptibility increases the risk for major depressive disorder (MDD), non-genetic protective factors may mitigate this risk. In a large-scale prospective study of US Army soldiers, we examined whether trait resilience and/or unit cohesion could protect against the onset of MDD following combat deployment, even in soldiers at high polygenic risk.
Data were analyzed from 3079 soldiers of European ancestry assessed before and after their deployment to Afghanistan. Incident MDD was defined as no MDD episode at pre-deployment, followed by a MDD episode following deployment. Polygenic risk scores were constructed from a large-scale genome-wide association study of major depression. We first examined the main effects of the MDD PRS and each protective factor on incident MDD. We then tested the effects of each protective factor on incident MDD across strata of polygenic risk.
Polygenic risk showed a dose–response relationship to depression, such that soldiers at high polygenic risk had greatest odds for incident MDD. Both unit cohesion and trait resilience were prospectively associated with reduced risk for incident MDD. Notably, the protective effect of unit cohesion persisted even in soldiers at highest polygenic risk.
Polygenic risk was associated with new-onset MDD in deployed soldiers. However, unit cohesion – an index of perceived support and morale – was protective against incident MDD even among those at highest genetic risk, and may represent a potent target for promoting resilience in vulnerable soldiers. Findings illustrate the value of combining genomic and environmental data in a prospective design to identify robust protective factors for mental health.
Every four years leading researchers gather to survey the latest developments in all aspects of group theory. Initially held in St Andrews, these meetings have become the premier forum for group theory across the whole of the UK. Since 1981, the proceedings of 'Groups St Andrews' have provided a regular snapshot of the state-of-the-art in group theory and helped to shape the direction of research in the field. This volume contains papers from the 2017 meeting held in Birmingham. It includes expository articles from the invited speakers, and further surveys contributed by the participants. Topics include: generation of finite simple groups, block theory, fusion systems, algebraic groups, one-relator groups, geometric group theory, and Beauville groups.
Objectives: Studies of neurocognitively elite older adults, termed SuperAgers, have identified clinical predictors and neurobiological indicators of resilience against age-related neurocognitive decline. Despite rising rates of older persons living with HIV (PLWH), SuperAging (SA) in PLWH remains undefined. We aimed to establish neuropsychological criteria for SA in PLWH and examined clinically relevant correlates of SA. Methods: 734 PLWH and 123 HIV-uninfected participants between 50 and 64 years of age underwent neuropsychological and neuromedical evaluations. SA was defined as demographically corrected (i.e., sex, race/ethnicity, education) global neurocognitive performance within normal range for 25-year-olds. Remaining participants were labeled cognitively normal (CN) or impaired (CI) based on actual age. Chi-square and analysis of variance tests examined HIV group differences on neurocognitive status and demographics. Within PLWH, neurocognitive status differences were tested on HIV disease characteristics, medical comorbidities, and everyday functioning. Multinomial logistic regression explored independent predictors of neurocognitive status. Results: Neurocognitive status rates and demographic characteristics differed between PLWH (SA=17%; CN=38%; CI=45%) and HIV-uninfected participants (SA=35%; CN=55%; CI=11%). In PLWH, neurocognitive groups were comparable on demographic and HIV disease characteristics. Younger age, higher verbal IQ, absence of diabetes, fewer depressive symptoms, and lifetime cannabis use disorder increased likelihood of SA. SA reported increased independence in everyday functioning, employment, and health-related quality of life than non-SA. Conclusions: Despite combined neurological risk of aging and HIV, youthful neurocognitive performance is possible for older PLWH. SA relates to improved real-world functioning and may be better explained by cognitive reserve and maintenance of cardiometabolic and mental health than HIV disease severity. Future research investigating biomarker and lifestyle (e.g., physical activity) correlates of SA may help identify modifiable neuroprotective factors against HIV-related neurobiological aging. (JINS, 2019, 25, 507–519)
Approximately 70% of the 30 000 known bee (Hymenoptera) species and most flower-visiting, solitary wasps (Hymenoptera) nest in the ground. However, nesting behaviours of most ground-nesting bees and wasps are poorly understood. Habitat loss, including nesting habitat, threatens populations of ground-nesting bees and wasps. Most ground-nesting bee and wasp studies implement trapping methods that capture foraging individuals, but provide little insight into the nesting preferences of these taxa. Some researchers have suggested that emergence traps may provide a suitable means by which to determine ground-nesting bee and wasp abundance. We sought to evaluate nest-site selection of ground-nesting bees and wasps using emergence traps in two study systems: (1) planted wildflower enhancement plots and fallow control plots in agricultural land; and (2) upland pine and hammock habitat in forests. Over the course of three years (2015–2017), we collected 306 ground-nesting bees and wasps across all study sites from emergence traps. In one study, we compared captures per trap between coloured pan traps and emergence traps and found that coloured pan traps captured far more ground-nesting bees and wasps than did emergence traps. Based on our emergence trap data, our results also suggest ground-nesting bees and wasps are more apt to nest within wildflower enhancement plots than in fallow control plots, and in upland pine habitats than in hammock forests. In conclusion, emergence traps have potential to be a unique tool to gain understanding of ground-nesting bee and wasp habitat requirements.
Getting a better understanding of the evolution and nucleosynthetic yields of the most metal-poor stars (Z ≲ 10−5) is critical because they are part of the big picture of the history of the primitive universe. Yet many of the remaining unknowns of stellar evolution lie in the birth, life, and death of these objects. We review stellar evolution of intermediate-mass Z ≤ 10−5 models existing in the literature, with a particular focus on the problem of their final fates. We emphasise the importance of the mixing episodes between the stellar envelope and the nuclearly processed core, which occur after stars exhaust their central He (second dredge-up and dredge-out episodes). The depth and efficiency of these episodes are critical to determine the mass limits for the formation of electron-capture SNe. Our knowledge of these phenomena is not complete because they are strongly affected by the choice of input physics. These uncertainties affect stars in all mass and metallicity ranges. However, difficulties in calibration pose additional challenges in the case of the most metal-poor stars. We also consider the alternative SN I1/2 channel to form SNe out of the most metal-poor intermediate-mass objects. In this case, it is critical to understand the thermally pulsing Asymptotic Giant Branch evolution until the late stages. Efficient second dredge-up and, later, third dredge-up episodes could be able to pollute stellar envelopes enough for the stars to undergo thermal pulses in a way very similar to that of higher initial Z objects. Inefficient second and/or third dredge-up may leave an almost pristine envelope, unable to sustain strong stellar winds. This may allow the H-exhausted core to grow to the Chandrasekhar mass before the envelope is completely lost, and thus let the star explode as an SN I1/2. After reviewing the information available on these two possible channels for the formation of SNe, we discuss existing nucleosynthetic yields of stars of metallicity Z ≤ 10−5 and present an example of nucleosynthetic calculations for a thermally pulsing Super-Asymptotic Giant Branch star of Z = 10−5. We compare theoretical predictions with observations of the lowest [Fe/H] objects detected. The review closes by discussing current open questions as well as possible fruitful avenues for future research.
Infants with prenatally diagnosed CHD are at high risk for adverse outcomes owing to multiple physiologic and psychosocial factors. Lack of immediate physical postnatal contact because of rapid initiation of medical therapy impairs maternal–infant bonding. On the basis of expected physiology, maternal–infant bonding may be safe for select cardiac diagnoses.
This is a single-centre study to assess safety of maternal–infant bonding in prenatal CHD.
In total, 157 fetuses with prenatally diagnosed CHD were reviewed. On the basis of cardiac diagnosis, 91 fetuses (58%) were prenatally approved for bonding and successfully bonded, 38 fetuses (24%) were prenatally approved but deemed not suitable for bonding at delivery, and 28 (18%) were not prenatally approved to bond. There were no complications attributable to bonding. Those who successfully bonded were larger in weight (3.26 versus 2.6 kg, p<0.001) and at later gestation (39 versus 38 weeks, p<0.001). Those unsuccessful at bonding were more likely to have been delivered via Caesarean section (74 versus 49%, p=0.011) and have additional non-cardiac diagnoses (53 versus 29%, p=0.014). There was no significant difference regarding the need for cardiac intervention before hospital discharge. Infants who bonded had shorter hospital (7 versus 26 days, p=0.02) and ICU lengths of stay (5 versus 23 days, p=0.002) and higher survival (98 versus 76%, p<0.001).
Fetal echocardiography combined with a structured bonding programme can permit mothers and infants with select types of CHD to successfully bond before ICU admission and intervention.
Supportive social relationships can reduce both psychological and physiological responses to stressful experiences. Recently, studies have also assessed the potential for social relationships to buffer the intergenerational transmission of stress. The majority of these studies, however, have focussed on social learning as a mechanism responsible for the intergenerational transmission of stress. Evidence of biological mechanisms is lacking. The objective of the current study was, therefore, to determine whether the association between maternal adverse childhood experiences (ACEs) and infant hypothalamic–pituitary–adrenal (HPA) axis function is mediated by maternal HPA axis function during pregnancy and moderated by social support. Data were from 243 mother–infant dyads enrolled in a prospective longitudinal cohort (the Alberta Pregnancy Outcomes and Nutrition Study). Maternal history of ACEs was retrospectively assessed while maternal perceived social support and salivary cortisol were assessed prospectively at 6–22 weeks gestation (Time 1) and 27–37 weeks gestation (Time 2), and infant cortisol reactivity to a laboratory stressor and maternal perceived social support were assessed at 5–10 months postnatal (Time 3). Results revealed that maternal HPA axis function during pregnancy mediated the effects of maternal ACEs on infant HPA axis reactivity, suggesting that the maternal HPA axis is a mechanism by which maternal early life stress is transmitted to offspring. Furthermore, social support in the prenatal and postnatal periods moderated the cascade from maternal ACEs to infant HPA axis reactivity. Specifically, prenatal social support moderated the association between ACEs and maternal HPA axis function during pregnancy, and postnatal social support moderated the association between maternal HPA axis function and infant cortisol reactivity. These findings highlight the social sensitivity of the HPA axis and suggest the utility of social relationships as an intervention target to reduce the effects of maternal early life stress on infant outcomes.
Background: Congenital Myasthenic Syndromes (CMS) are heterogeneous disorders caused by genetically determined structural or functional differences in proteins involved with the neuromuscular junctions. Clinical and molecular genetics studies of CMS patients have revealed significant locus heterogeneity; there are 21 known genes related to CMS, but other genes may mimic the phenotype, justifying the use of a multi-gene panel for genetic testing Methods: Our group developed custom sequence capture probes designed to flank 27 different genes associated with CMS, including enrichment for all coding exons as well the flanking intronic regions. We enrolled 20 patients from the paediatric and adult neuromuscular clinic with a clinical phenotype of CMS. Using custom analytical, we -assessed the sequence variants and exon-level CNVs for each patient. Results: Thirteen male and seven female patients with median age of 12.25 years (range 1.5-39y) were assessed. We identified missense and CNVs in 17 patients, including established pathogenic mutations confirming the diagnosis in 5 patients Conclusions: The use of Next Generation Sequence with CNV for CMS can help determine the underlying causes of most CMS disorders and allow appropriate medical treatment, refined genetic counseling, and improved understanding of prognosis, justifying the implementation in the standard clinical screening of CMS.