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Purpose of Review: Myotonic dystrophy type 2 (DM2) is a genetic disorder belonging to the spectrum of myotonic dystrophies. DM2 is characterized by progressive muscle weakness, wasting and muscle pain (myalgia), but can also affect many other organ systems. In this review, we provide an updated overview on the research literature on DM2 with a focus on the management of multisystemic involvement and atypical clinical phenotypes., Recent Findings: Recent studies have focused on different aspects of multisystemic involvement. Early and severe cardiac involvement can occur in DM2 and needs to be managed appropriately. Diabetes has been shown to be more common in DM2 than in DM1, while a combination of symptoms (cataracts, myotonia, tremor) can be used to raise clinical suspicion and initiate genetic testing for DM2. Autoimmune disease has been shown to occur in up to one-third of DM2 patients, possibly due to altered immune pathways. New evidence also suggests a childhood-onset phenotype presenting with foot deformities., Summary: The multisystemic aspects of the disease require a multidisciplinary approach for some patients, most likely even including state-of-the-art cardiac and brain imaging to detect and treat complications earlier. Of note, our concept of DM2 as an adult-onset disease is somewhat challenged by evidence suggesting a few pediatric DM2 patients and possibly anticipation, at least in some DM2 families. More studies, including larger cohorts, are needed to better understand this possible early-onset DM2 phenotype variant., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: Myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2) are genetic disorders affecting skeletal and smooth muscle, heart, brain, eyes, and other organs. The multisystem involvement and disease variability of myotonic dystrophy have presented challenges for clinical care and research. This article focuses on the diagnosis and management of the disease. In addition, recent advances in characterizing the diverse clinical manifestations and variability of the disease are discussed., Recent Findings: Studies of the multisystem involvement of myotonic dystrophy, including the most lethal cardiac and respiratory manifestations and their molecular underpinnings, expand our understanding of the myotonic dystrophy phenotype. Advances have been made in understanding the molecular mechanisms of both types of myotonic dystrophy, providing opportunities for developing targeted therapeutics, some of which have entered clinical trials in DM1., Summary: Continued efforts focus on advancing our molecular and clinical understanding of DM1 and DM2. Accurately measuring and monitoring the diverse and variable clinical manifestations of myotonic dystrophy in clinic and in research is important to provide adequate care, prevent complications, and find treatments that improve symptoms and life quality., (Copyright © 2022 American Academy of Neurology.)

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., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale: Myotonic dystrophy type 1 (DM1) is an autosomal-dominant disorder associated with a short life expectancy and various symptoms, including grip myotonia. Even though grip myotonia decreases quality of life, activities of daily living (ADLs), and work performance, very few interventions provide symptomatic relief., Patient Concerns: In this case report, we present a patient with DM1 and gradually worsening grip myotonia. A 35-year-old woman developed grip myotonia at age 27. She had no underlying diseases or family history of relevant conditions, including DM1. She was unresponsive to medication for several years., Diagnosis: Her symptoms gradually worsened, and she was finally diagnosed with DM1 via genetic, neurologic, and laboratory testing in a tertiary hospital at age 32. She tried several medication therapies; however, she stopped medication at age 34 due a perceived poor response and several adverse events., Intervention: At the age of 35, she underwent 29 sessions (10 minutes per session) of electroacupuncture therapy on TE9 acupuncture point with 120 Hz electrical stimulation over 3 months., Outcomes: After 3 months, relaxation time after maximal voluntary isometric contraction decreased from 59 to 2 seconds with treatment. Her Michigan Hand Outcomes Questionnaire score improved (total score, 66.6-75.9; ADL sub-score, 59.7-73.6; function sub-score, 70-90; satisfaction sub-score, 75-91.7). Her Measure Yourself Medical Outcome Profile 2 score also improved from 4.33 to 2. There were no serious adverse events., Lessons: Electroacupuncture is a potential treatment modality and produced an immediate antimyotonic effect, and cumulative long-term treatment effect, in a patient with DM1 and grip myotonia. Other notable treatment outcomes included improving relaxation time, hand function, ADLs, and overall satisfaction. Electroacupuncture is a potential treatment modality for patients with DM1 and grip myotonia. Further prospective clinical studies are warranted to confirm this hypothesis.

Objective: To investigate intrarater reliability and concurrent and construct validity of muscle strength, balance, and functional mobility measures in individuals with noncongenital myotonic dystrophy type 1 (DM1)., Methods: Seventy-eight adults with noncongenital DM1 participated in visit 1, and 73 of the them participated in visit 2 separated by 1 to 2 weeks. The assessments consisted of muscle strength tests with handheld dynamometry (HHD) and stationary dynamometry in the lower limb. The balance tests consisted of the step test, Timed Up and Go test, feet-together stance, tandem stance, 1-leg stance, and modified Clinical Test of Sensory Integration and Balance on a balance platform. The functional mobility tests consisted of the 10-m walk test (10mWT) and 10-times Sit-to-Stand test., Results: The HHD and stationary dynamometry had sufficient intrarater reliability for most muscle groups on a group (SEM % ≤15%) and individual (minimal detectable difference [MDD 95% ] ≤30%) level, but the HHD was most reliable. Stationary dynamometry measured a higher torque than HHD for all extensor muscles, but for single individuals, none of the devices were favored. Overall, intrarater reliability and validity were sufficient only for the dynamic balance tests, not the static balance tests. Both functional mobility tests were sufficiently reliable and valid, but the 10mWT was most reliable., Conclusion: Overall, HHD is recommended as a reliable and valid tool for single individuals and for flexor muscles on a group level. For balance assessments, the dynamic balance tests are recommended as the most valid and reliable balance tests. Both functional mobility tests are recommended for valid and reliable outcomes, but the 10mWT was superior for reliability., (© 2020 American Academy of Neurology.)

Purpose of Review: This article describes the clinical features, pathogenesis, prevalence, diagnosis, and management of myotonic dystrophy type 1 and myotonic dystrophy type 2., Recent Findings: The prevalence of myotonic dystrophy type 1 is better understood than the prevalence of myotonic dystrophy type 2, and new evidence indicates that the risk of cancer is increased in patients with the myotonic dystrophies. In addition, descriptions of the clinical symptoms and relative risks of comorbidities such as cardiac arrhythmias associated with myotonic dystrophy type 1 have been improved., Summary: Myotonic dystrophy type 1 and myotonic dystrophy type 2 are both characterized by progressive muscle weakness, early-onset cataracts, and myotonia. However, both disorders have multisystem manifestations that require a comprehensive management plan. While no disease-modifying therapies have yet been identified, advances in therapeutic development have a promising future.

Rationale: Myotonic dystrophy is a progressive multisystem genetic heterogeneous disorder. General anesthesia with opioids increases the risk of prolonged postanesthetic respiratory recovery in myotonic dystrophy patients., Patient Concerns: A 20-year-old previously healthy woman was transferred to our emergency department for further workup of respiratory failure, and massive ascites with abscess caused by endometriosis. Hypercapnic respiratory failure persisted under intensive care unit (ICU) management, but finally improved after cessation of fentanyl as a sedative agent., Diagnosis: Myotonic dystrophy type 1., Interventions: Massive ascites with abscess was accordingly managed by drainage, antibiotics, and an antifungal agent. Myotonic dystrophy type 1 was confirmed after molecular genetic testing revealed a cytosine-thymine-guanine repeat length of 400 to 450 in the DMPK gene., Outcomes: The patient was discharged without complications on hospital day 69., Lessons: Myotonic dystrophy should be considered when hypercapnic respiratory failure persists in sedated ICU patients. Opioids should not be used for perioperative management of patients with myotonic dystrophy.

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.

Objective: Functional electrical stimulation (FES) is a new rehabilitative approach that combines electrical stimulation with a functional task. This pilot study evaluated the safety and effectiveness of FES lower extremity training in myotonic dystrophy type 1., Design: This is a controlled pilot study that enrolled 20 patients with myotonic dystrophy type 1 over 2 years. Eight patients (age, 39-67 years) fulfilled the inclusion criteria. Four participants performed FES cycling training for 15 days (one daily session of 30 minutes for 5 days a week). A control group, matched for clinical and genetic variables, who had contraindications to electrical stimulation, performed 6 weeks of conventional resistance and aerobic training. The modified Medical Research Council Scale and functional assessments were performed before and after treatment. Cohen d effect size was used for statistical analysis., Results: Functional electrical stimulation induced lower extremity training was well tolerated and resulted in a greater improvement of tibialis anterior muscle strength (d = 1,583), overall muscle strength (d = 1,723), and endurance (d = 0,626) than conventional training., Conclusions: Functional electrical stimulation might be considered a safe and valid tool to improve muscle function, also in muscles severely compromised in which no other restorative options are available. Confirmation of FES efficacy through further clinical trials is strongly advised.

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., (© 2016 American Academy of Neurology.)

Purpose of Review: Myotonic dystrophies type 1 and type 2 are progressive multisystem genetic disorders with clinical and genetic features in common. Myotonic dystrophy type 1 is the most prevalent muscular dystrophy in adults and has a wide phenotypic spectrum. The average age of death in myotonic dystrophy type 1 is in the fifth decade. In comparison, myotonic dystrophy type 2 tends to cause a milder phenotype with later onset of symptoms and is less common than myotonic dystrophy type 1. Historically, patients with myotonic dystrophy type 1 have not received the medical and social input they need to maximize their quality and quantity of life. This review describes the improved understanding in the molecular and clinical features of myotonic dystrophy type 1 as well as the screening of clinical complications and their management. We will also discuss new potential genetic treatments., Recent Findings: An active approach to screening and management of myotonic dystrophies type 1 and type 2 requires a multidisciplinary medical, rehabilitative and social team. This process will probably improve morbidity and mortality for patients. Genetic treatments have been successfully used in in-vitro and animal models to reverse the physiological, histopathological and transcriptomic features., Summary: Molecular therapeutics for myotonic dystrophy will probably bridge the translational gap between bench and bedside in the near future. There will still be a requirement for clinical screening of patients with myotonic dystrophy with proactive and systematic management of complications.

Purpose of Review: The myotonic dystrophies (DM1 and DM2) are the paradigm for RNA toxicity in disease pathogenesis. The emphasis of this review will be on recent developments and issues in understanding the pathogenesis of DM1 and how this is driving the accelerated pace of translational and therapeutic developments., Recent Findings: RNA toxicity in myotonic dystrophy is now associated with bi-directional antisense transcription, dysregulation of microRNAs and potentially non-ATG-mediated translation of homopolymeric toxic proteins. The role of other RNA-binding proteins beyond MBNL1 and CUGBP1, such as Staufen 1 and DDX5, are being identified and studied with respect to their role in myotonic dystrophy. New functions for MBNL1 in miR-1 biogenesis might have a clinically relevant role in myotonic dystrophy cardiac conduction defects and pathology. Advances are being made in identifying and characterizing small molecules with the potential to disrupt CUG-MBNL1 interactions., Summary: Mechanisms of RNA toxicity are moving beyond a simplistic 'foci-centric' view of DM1 pathogenesis as a spliceopathy due to MBNL1 sequestration. Therapeutic development for myotonic dystrophy is moving rapidly with the development of antisense and small molecule therapies. Clinically, significant emphasis is being placed on biomarker discovery and outcome measures as an essential prelude to clinical trials.

Objective: Myotonic dystrophy type 1 (DM1) is the most frequent muscular dystrophy in adults. DM1 is a multisystem disorder also affecting the heart with an increased incidence of sudden death, which has been explained with the common impairment of the conduction system often requiring pacemaker implantation; however, the occurrence of sudden death despite pacemaker implantation and the observation of major ventricular arrhythmias generated the hypothesis that ventricular arrhythmias may play a causal role as well. The aim of the study was to assess the 2-year cumulative incidence and the value of noninvasive and invasive findings as predictive factors for sudden death, resuscitated cardiac arrest, ventricular fibrillation, sustained ventricular tachycardia and severe sinus dysfunction or high-degree atrioventricular block., Methods/design: More than 500 DM1 patients will be evaluated at baseline with a clinical interview, 12-lead ECG, 24-h ECG and echocardiogram. Conventional and nonconventional indications to electrophysiological study, pacemaker, implantable cardioverter defibrillator or loop recorder implantation have been developed. In the case of an indication to electrophysiological study, pacemaker, implantable cardioverter defibrillator or loop recorder implant at baseline or at follow-up, the patient will be referred for the procedure. At the end of 2-year follow-up, all candidate prognostic factors will be tested for their association with the endpoints., Trial Registration: ClinicalTrials.gov ID NCT00127582., Conclusion: The available evidence supports the hypothesis that both bradyarrhythmias and tachyarrhythmias may cause sudden death in DM1, but the course of cardiac disease in DM1 is still unclear. We expect that this large, prospective, multicenter study will provide evidence to improve diagnostic and therapeutic strategies in DM1.

Over the past 15 years, molecular genetic advances have led to new approaches for evaluation of neurogenetic disease. New diagnostic tests are available, and in some cases new diseases have been defined. However, effective use of these new tests still relies on solid clinical assessment to prioritize testing and interpret results. This review presents applications of genetic advances to a series of neurogenetic disorders, emphasizing the specific uses of genetic testing and the clinical questions that may arise. The rapid expansion in molecular diagnostics and genomics has fundamentally changed the approach to neurogenetic illnesses. Use of molecular biologic techniques has elucidated new disease mechanisms and allowed the application of genetic concepts to classically nongenetic illnesses. This has led to a wealth of new clinical information and created new dilemmas in patient care. In addition, it has brought into common usage a series of clinical genetic terms, such as variable expressivity (the range of phenotypic features in which the same disease can manifest) and anticipation (the progressively earlier age of onset of a specific disease in a family). This review provides a practical approach for neurogenetic evaluation of individuals who are likely to present in neuro-ophthalmologic practices with inherited ataxias, myotonic dystrophy, oculopharyngeal dystrophy, and Parkinson disease.

The recent development of recombinant human growth hormone (GH) and insulin-like growth factor 1 (IGF-1) has provided the opportunity to study the effects of these growth factors in humans. The majority of studies have been performed in healthy young and older adults. Both GH and IGF-1 have shown very positive effects on muscle protein anabolism. Relatively few side effects have developed. Initial studies have shown a beneficial effect of GH in reversing the catabolic actions of oral prednisone, and GH treatment has led to an increase in muscle mass and protein synthesis in pilot studies of myotonic dystrophy. Combination therapy in normal subjects using both GH and IGF-1 has shown encouraging results. There is a greater enhancement of protein anabolism during combined treatment than there is with either agent alone, and concomitant therapy with GH diminished the side effects of IGF-1. It is now feasible to consider therapeutic trials in patients. Future studies of GH and IGF-1 treatment in patients with primary muscle disease and in patients receiving long-term corticosteroid therapy are needed.

To evaluate the progression of conduction system disease in myotonic muscular dystrophy, nine patients underwent serial electrophysiologic studies at a mean of 35 months apart. At the initial study, seven patients had first-degree atrioventricular block and three of these seven had disease in the His-Purkinje system (HV greater than 55 msec). At the second study, seven patients had prolonged HV intervals, and during the almost 3-year period, HV intervals increased by at least 5 msec in all seven patients. No electrophysiologic or electrocardiographic measures could be found that correlated with progression of conduction disease in these patients. Because of the failure of electrophysiologic measures to predict progression of conduction disease in these patients, electrophysiologic studies are recommended only for symptomatic patients. If significant disease is found in either impulse formation or conduction, permanent pacemaker therapy is warranted.