Molecular Pathology of Myotonic Dystrophy Type 1 in Iceland.

BACKGROUND: Myotonic Dystrophy type 1 (DM1) is an autosomal dominant disease with anticipation due to increased number of CTG repeats in the DMPK gene. METHODS: This retrospective, cohort study in Iceland assessed prevalence of DM1, molecular pathology, and patient ascertainment. Data was collected from all major hospitals in Iceland, Medical Director of Health, and independent clinics. Cohort criteria were diagnosis of DM1 on January 1, 2021, or time of death. Population-based Icelandic Genealogy Database of the Genetical Committee at the University of Iceland was used for genealogy. RESULTS: In Iceland, 221 individuals, including 19 obligate carriers, had been diagnosed with DM1 of which 144 were alive giving a point prevalence of 39 per 100,000 (four times the world average of 9.3). Genealogy analysis identified 45 first-degree families. Age-adjusted prevalence ranged between 11 and 66 per 100,000. Average potential years of life lost were 20.5 per person. Where information was available, 63% of ascertainment was based on family history in cascade testing. CONCLUSION: The differences in age-adjusted prevalence suggest that the overall point prevalence is an underestimation due to underdiagnosis in younger age groups and lethality in oldest age group. Our data supports use of cascade testing to improve DM1 ascertainment.

Hypogammaglobulinemia and infection risk in myotonic dystrophy type 1.

INTRODUCTION/AIMS: Hypogammaglobulinemia is a common yet under-recognized feature of myotonic dystrophy type 1 (DM1). The aims of our study were to determine the frequency of immunoglobulin G (IgG) deficiency in our cohort, to examine the association between immunoglobulin levels and cytosine-thymine-guanine (CTG) repeat length in the DMPK gene, and to assess whether IgG levels are associated with an increased risk of infection in DM1 patients. METHODS: We conducted a single-center, retrospective cross-sectional study of 65 adult patients with DM1 who presented to the Neuromuscular Clinic at Concord Repatriation General Hospital, Sydney, Australia, between January 2002 and January 2022. We systematically collected and analyzed clinical, laboratory, and genetic data for all patients with available serum electrophoresis and/or IgG level results. RESULTS: Forty-one percent of DM1 patients had IgG deficiency despite normal lymphocyte counts, IgA, IgM, and albumin levels. There was an association between CTG repeat expansion size and the degree of IgG deficiency (F = 6.3, p = .02). There was no association between IgG deficiency and frequency of infection in this group (p = .428). DISCUSSION: IgG deficiency is a frequent occurrence in DM1 patients and is associated with CTG repeat expansion size. Whether hypogammaglobulinemia is associated with increased infection risk in DM1 is unclear. A prospective multicenter cohort study is needed to evaluate this.

The Study of the Inheritance Mechanisms of Myotonic Dystrophy Type 1 (DM1) in Families from the Republic of North Ossetia-Alania.

Myotonic dystrophy type 1 (DM1) is a multisystem disorder with progressive myopathy and myotonia. The clinical study was conducted in the Republic of North Ossetia-Alania (RNOA), and in it 39 individuals from 17 unrelated families were identified with DM1. Clinical presentations varied, including muscle weakness, fatigue, intellectual disability, hypersomnia, ophthalmological abnormalities, and alopecia. Using clinical and genotyping data, we confirmed the diagnosis and enabled the study of CTG-repeat anticipation and DM1 prevalence in the Ossetian and Ingush populations. CTG expansion correlated with age of onset, with clinical severity, and with offspring showing more severe symptoms than parents. In many families, the youngest child had a more severe DM1 phenotype than older siblings. The prevalence was 14.17 per 100,000 in Ossetians and 18.74 per 100,000 in Ingush people, aligning with global data. Segregation analysis showed a higher frequency of maternal transmission. The study highlights the clinical and genetic heterogeneity of DM1 and its dependence on repeat expansion and paternal and maternal age.

Cancer Risk in Patients With Muscular Dystrophy and Myotonic Dystrophy: A Register-Based Cohort Study.

BACKGROUND AND OBJECTIVES: Muscular dystrophies and myotonic disorders are genetic disorders characterized by progressive skeletal muscle degeneration and weakness. Epidemiologic studies have found an increased cancer risk in myotonic dystrophy, although the cancer risk spectrum is poorly characterized. In patients with muscular dystrophy, the cancer risk is uncertain. We aimed to determine the overall cancer risk and cancer risk spectrum in patients with muscular dystrophy and myotonic dystrophy using data from the Swedish National registers. METHODS: We performed a matched cohort study in all patients with muscular dystrophy or myotonic dystrophy born in Sweden 1950-2017 and 50 matched comparisons by sex, year of birth, and birth county per individual. The association with cancer overall and specific malignancies was estimated using stratified Cox proportional hazard models. RESULTS: We identified 2,355 and 1,968 individuals with muscular dystrophy and myotonic dystrophy, respectively. No increased overall cancer risk was found in muscular dystrophy. However, we observed an increased risk of astrocytomas and other gliomas during childhood (hazard ratio [HR] 8.70, 95% CI 3.57-21.20) and nonthyroid endocrine cancer (HR 2.35, 95% CI 1.03-5.34) and pancreatic cancer (HR 4.33, 95% CI 1.55-12.11) in adulthood. In myotonic dystrophy, we found an increased risk of pediatric brain tumors (HR 3.23, 95% CI 1.16-9.01) and an increased overall cancer risk in adults (HR 2.26, CI 1.92.2.66), specifically brain tumors (HR 10.44, 95% CI 7.30-14.95), thyroid (HR 3.92, 95% CI 1.70-9.03), and nonthyroid endocrine cancer (HR 7.49, 95% CI 4.47-12.56), endometrial (HR 8.32, 95% CI 4.22-16.40), ovarian (HR 4.00, 95% CI 1.60-10.01), and nonmelanoma skin cancer (HR 3.27, 95% CI 1.32-8.13). DISCUSSION: Here, we analyze the cancer risk spectrum of patients with muscular dystrophy and myotonic dystrophy. To the best of our knowledge, this is the first report of an increased risk for CNS tumors in childhood and adult nonthyroid endocrine and pancreatic cancer in muscular dystrophy. Furthermore, for myotonic dystrophy, we confirmed previously reported associations with cancer and expanded the cancer spectrum, finding an unreported increased risk for nonthyroid endocrine cancer. Additional studies confirming the cancer risk and delineating the cancer spectrum in different genetic subtypes of muscular dystrophies are warranted before considering altered cancer screening recommendations than for the general population.

Prevalence of cardiovascular implantable electronic devices in children with type 1 myotonic dystrophy.

INTRODUCTION/AIMS: Type 1 myotonic dystrophy (DM1) is a neuromuscular disorder of multiple organ systems with important electrophysiologic (EP) manifestations, leading to a cumulative incidence of sudden death of 6.6%. Due to genetic anticipation, there is a pediatric subset of this patient population. However, most EP research on DM1 patients has been in adults, making cardiac care for pediatric patients difficult and directed by adult guidelines which often leads to cardiovascular implantable electronic device (CIED) implants. We sought to investigate the prevalence of CIEDs in the pediatric DM1 population. METHODS: The Vizient® Clinical Data Base was queried from October 2019 to October 2023 for admissions with and without ICD-10 code for myotonic dystrophy (G71.11), with and without codes for presence of a pacemaker or ICD (Z95.0, Z95.810). Patients who were identified were stratified by age: Pediatric (0-21 years) and Adult (22-50 years). RESULTS: Prevalence of CIED in pediatric DM1 was 2.1% and in adult DM1 was 15.8%. When comparing to pediatric and adult patients with CIED and without DM1, the odds ratio for CIED in pediatric DM1 was 48.8, compared to 23.3 for CIED in adult DM1. DISCUSSION: There are pediatric DM1 patients who have received CIED despite a lack of data to inform this decision-making. Further research will be important to ensure appropriate use of CIED in this population and to develop appropriate guidelines to direct management.

Natural history of cardiac involvement in myotonic dystrophy type 1 - Emphasis on the need for lifelong follow-up.

BACKGROUND: Cardiac involvement represents a major cause of morbidity and mortality in patients with myotonic dystrophy type 1 (DM1) and prevention of sudden cardiac death (SCD) is a central part of patient care. We investigated the natural history of cardiac involvement in patients with DM1 to provide an evidence-based foundation for adjustment of follow-up protocols. METHODS: Patients with genetically confirmed DM1 were identified. Data on patient characteristics, performed investigations (12 lead ECG, Holter monitoring and echocardiography), and clinical outcomes were retrospectively collected from electronic health records. RESULTS: We included 195 patients (52% men) with a mean age at baseline evaluation of 41 years (range 14-79). The overall prevalence of cardiac involvement increased from 42% to 66% after a median follow-up of 10.5 years. There was a male predominance for cardiac involvement at end of follow-up (74 vs. 44%, p < 0.001). The most common types of cardiac involvement were conduction abnormalities (48%), arrhythmias (35%), and left ventricular systolic dysfunction (21%). Only 17% of patients reported cardiac symptoms. The standard 12­lead ECG was the most sensitive diagnostic modality and documented cardiac involvement in 24% at baseline and in 49% at latest follow-up. However, addition of Holter monitoring and echocardiography significantly increased the diagnostic yield with 18 and 13% points at baseline and latest follow-up, respectively. Despite surveillance 35 patients (18%) died during follow-up; seven due to SCD. CONCLUSIONS: In patients with DM1 cardiac involvement was highly prevalent and developed during follow-up. These findings justify lifelong follow-up with ECG, Holter, and echocardiography. CLINICAL PERSPECTIVE: What is new? What are the clinical implications?

Myotonic dystrophy type 1 in South Korea: a comprehensive analysis of cancer and comorbidity risks.

BACKGROUND AND PURPOSE: Myotonic dystrophy type 1 (DM1) is an inherited neuromuscular disorder characterized by myotonia and progressive muscle weakness. Beyond the primary symptoms, there is growing concern regarding a higher incidence of certain comorbidities in DM1 patients, including cancer, diabetes, thyroid dysfunction, and cataracts. This study was designed to examine the occurrence of these conditions among patients diagnosed with DM1 in South Korea, using data from the National Health Insurance Service database. METHODS: The study undertook a comprehensive review of 3,842 patients diagnosed with DM1 between 2012 and 2018. We assessed the incidence of cancer and the prevalence of diabetes, thyroid dysfunction, and cataracts among these patients, comparing their rates to those in the general population. RESULTS: In the study cohort, 463 out of 3,842 DM1 patients (12.04%) were diagnosed with cancer, indicating a substantial elevation in cancer risk with an overall standard incidence ratio of 1.9 (95% CI = 1.6-2.3, p < 0.01) when compared to the expected rates in the general population. Moreover, the prevalence of diabetes (15.2%) and thyroid dysfunction (17.6%) was noteworthy in the DM1 population. The mean age at which DM1 patients underwent cataract surgery was 55.07 years, noticeably younger than the mean age of 69.25 years for cataract surgery in the general population. CONCLUSIONS: DM1 patients have a noteworthy occurrence of several comorbidities such as cancer, diabetes, thyroid dysfunction, and earlier cataract surgery. This highlights the importance of a comprehensive and integrative approach to the management and treatment of DM1, going beyond addressing only the primary neuromuscular symptoms. More research is required to understand the underlying mechanisms contributing to these comorbidities in DM1 patients, which may inform preventative measures and guide improvements in patient care.

Impact of gastrointestinal and urological symptoms in children with myotonic dystrophy type 1.

Gastrointestinal and urological symptoms are frequently reported by people with myotonic dystrophy type 1 (DM1) but have remained understudied. In a cross-sectional study, frequency, nature, treatment and impact of gastrointestinal and urological symptoms in children with DM1 aged 5-18 years were assessed. We included 58 children (30 males, 28 females) with a mean age of 13 years; 74.1 % reported at least one gastrointestinal symptom. Abdominal pain was the most frequently reported symptom (51.7 %), followed by dysphagia (41.8 %), diarrhoea (36.2 %), encopresis (36.0 %), constipation (32.7 %), bloating and flatulence (both 25.9 %). The most frequently reported urological symptoms were difficulty with toilet training (59.3 %), urinary incontinence (22.0 %), enuresis nocturna (10.3 %) and voiding (23.5 % hesitancy, 4.8 % intermittency and 13.8 % dysuria). The majority considered urological and gastrointestinal symptoms to have a negative influence on their daily life; 22.4 % of parents reported severe influence on daily family life (shame, social restrictions, school absence and concerns for their children's future). Considering the high prevalence of urological and gastrointestinal symptoms in children with DM1 and their influence on daily life it is key to correctly recognize, diagnose and treat these symptoms. We recommend screening for gastrointestinal and urological symptoms in the standard of care for children with DM1.

Myotonic dystrophy type 1 (Steinert disease): 29 years of experience at a tertiary pediatric hospital.

BACKGROUND: Myotonic dystrophy type 1 (DM1) is a multisystemic disorder caused by the expansion of a noncoding triplet repeat. METHODS: A cross-sectional study was performed to characterize pediatric patients with DM1 followed in a tertiary hospital over the last 29 years, comparing the congenital and the childhood/juvenile-onset forms. RESULTS: Thirty-seven patients (59.5 % male) were included, with a median age at the latest assessment of 16.8 years and a median follow-up of 7.7 years. Eleven patients were lost to follow-up, and two died. Twenty-five had congenital DM1 (CDM1), and this form had significantly higher triplet repeat length, history of polyhydramnios, lower median age at diagnosis, and first and last assessment. Common symptoms included distal skeletal muscle weakness (75.7 %) and facial involvement (94.6 %), along with dysphonia/dysarthria (73.0 %) and myotonia (73.0 %). Delayed independent ambulation frequency was significantly higher for CDM1 cases. Skeletal deformities affected 54.1 %, with talipes equinovarus and scoliosis occurring exclusively in CDM1 patients. Cognitive deficit was present in 75.7 % of cases. Polysomnograms revealed seven cases of obstructive sleep apnea and two of hypoventilation. Noninvasive ventilation was used in nine cases, and three had recurrent respiratory infections. The cardiovascular system was affected in 21.6 % of cases. Gastrointestinal issues included constipation (24.3 %), feeding difficulties (16.2 %), and cholelithiasis (5.4 %). Cataracts, epilepsy, and diabetes mellitus were reported in two cases each. CONCLUSION: Our study highlights the diverse spectrum of severity and multiorgan involvement of DM1 in pediatric patients. It underscores the importance of establishing a pediatric-specific standard of care to enhance health outcomes through comprehensive multidisciplinary management.

Open Bite Malocclusion and Orofacial Dysfunction in Patients with Myotonic Dystrophy Type 1 and Duchenne Muscular Dystrophy.

Open bite (OB) is a common malocclusion in individuals with orofacial dysfunction and syndromes, especially in neuromuscular diseases. OBJECTIVES: The objectives were to explore the prevalence of OB in myotonic dystrophy type 1 (DM1) and Duchenne muscular dystrophy (DMD) and to create and compare orofacial dysfunction profiles. METHODS: In this database study, 143 individuals with DM1 and 99 with DMD were included. The Mun-H-Center questionnaire and observation chart were used together with the Nordic Orofacial Test -Screening (NOT-S) to create orofacial dysfunction profiles. OB was categorised as: lateral (LOB); anterior (AOB); severe anterior (AOBS); or both types of anterior OB (AOBTot). Descriptive and multivariate statistics were used to compare the OB prevalence and to study associations with orofacial variables, respectively. RESULTS: There was a statistically significant difference in OB prevalence between the DM1 (37%) and DMD (49%) groups (p = 0.048). LOB was seen in < 1% of DM1 and 18% of DMD. LOB was associated with macroglossia and closed mouth posture, AOB with hypotonic lips, and open mouth posture and AOBS with hypotonic jaw muscles. The orofacial dysfunction profiles showed similar patterns, although the mean NOT-S total scores for DM1 and DMD were 4.2±2.8 (median 4.0, min-max 1-8) and 2.3±2.0 (median 2.0, min-max 0-8), respectively. LIMITATIONS: The two groups were not age- or gender-matched. CONCLUSION: OB malocclusion is common in patients with DM1 and DMD and is associated with different types of orofacial dysfunction. This study highlights the need for multi-disciplinary assessments to support tailored treatment strategies that improve or sustain orofacial functions.

Do classical and computerized cognitive tests have equal intrarater reliability in myotonic dystrophy type 1?

Myotonic dystrophy type 1 (DM1) is a multisystemic inherited neuromuscular disease leading to central nervous system symptoms, including cognitive impairments, among multiple other symptoms. However, information is presently lacking regarding the psychometric properties of neuropsychological tests and promising computerized cognitive tests, such as the Cambridge Neuropsychological Test Automated Battery (CANTABⓇ). This type of information is critical to improve clinical trial readiness and provide knowledge of DM1 natural history. The aims of the present study were (1) to document the intrarater reliability of classic paper-pencil tests assessing visuospatial working memory, cognitive flexibility, attention, episodic memory and apathy, and (2) to compare these findings with their equivalent computerized automated tests from the CANTABⓇ. Thirty participants were seen twice at four-week intervals. Results showed that the Stroop Color and Word Test (ICC = 0.741-0.869) and the Ruff 2 & 7 (ICC = 0.703-0.871) appear to be reliable paper-and-pencil tests in the DM1 population. For the CANTABⓇ, a similar observation was made for the Multitasking test (ICC = 0.588-0.792). Further studies should explore the applicability and concurrent validity of the CANTAB® and classic neuropsychological assessments in additional cohorts of DM1 patients.

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.

Central Bradypnea and Ataxic Breathing in Myotonic Dystrophy Type 1 - A Clinical Case Report.

BACKGROUND: The occurrence of obstructive and central sleep apnea syndromes, ventilator pump failure and reduced hypercapnic ventilatory drive in myotonic dystrophy type 1 (DM1) is well established, and there are indications for an impairment of the hypoxic ventilator drive, too. Yet, it is still unknown, to which extent the respiratory rhythm is affected by DM1, thus if a central bradypnea, cluster breathing or ataxic ("Biot's") breathing can occur. Additionally, the causes of the impairment of the central respiratory drive in DM1 are not known. CASE PRESENTATION: We present the case of a tracheotomized female patient with DM1 with central bradypnea and ataxic breathing. A 57-year-old woman with DM1 was admitted to our Neurointensive Care Unit (NICU) due to refractory tracheobronchial retention of secretions resulting from aspiration of saliva. Due to a combination of chronic hypercapnic respiratory failure, severe central bradypnea with a minimal breathing frequency of 3 per minute and ataxic breathing a pressure-controlled home ventilation was initiated. CONCLUSIONS: In our patient central bradypnea and ataxic breathing possibly were respiratory sequale of DM1, that may have been caused by pontine white matter lesions affecting the pontine respiratory nuclei. From a clinical viewpoint, polygraphy is a suitable tool to objectify disorders of the respiratory rhythm in DM1 even in tracheotomized patients. Clinical studies combining respiratory diagnostics as polygraphy, transcutaneous capnometry and blood gas analysis with brain magnetic resonance imaging (MRI) are required to better understand disorders of respiratory regulation in DM1, and to identify their anatomical correlates.

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.

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.

Prevalence of urinary incontinence and other pelvic floor disorders in women with myotonic dystrophy type 1.

Myotonic dystrophy type 1 (DM1) is a neuromuscular disease that can affect the pelvic floor muscles but few studies have investigated pelvic floor disorders, including urinary incontinence. The main purpose of this study was to document the prevalence, characteristics, and impacts of urinary incontinence and other pelvic floor disorders in women with DM1. Associations between pelvic floor disorders and phenotypes, considering age and parity, were explored. Eighty adult women aged 47,1±13,7 years old participated in a cross-sectional study using validated questionnaires, including the International Consultation Incontinence Questionnaire - Urinary Incontinence short form (ICIQ-UI-SF)), the Pelvic Floor Disorder Inventory (PFDI), and the Pelvic Floor Impact Questionnaire short form (PFIQ-SF). The mean score for the ICIQ-UI-SF was 4.3. The mean scores for the subscales of the PFDI were 36.8 for the urinary distress inventory, 74.1 for the colorectal-anal distress inventory, and 43.8 for the pelvic organ prolapse distress inventory. A total of 60% of women reported urinary incontinence and 56.3% anal incontinence. Pelvic prolapse symptoms (>1 symptom) were reported by 25% of women. Findings reveal high prevalence and significant related impacts of these disorders. This provides evidence regarding the importance of screening for these disorders in a clinical setting and the need to explore treatment approaches.

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.

Gender effect on onset, prevalence and surgical treatment of cataract in patients with Myotonic Dystrophy type 1.

Myotonic Dystrophy type 1 (DM1) is the most common muscular dystrophy in adults, affecting 1:8000 individuals. It is a multi-systemic disorder involving muscle, heart, endocrine and respiratory apparatus and eye. The eye symptoms can include ptosis, external ophthalmoplegia, epiphora, and early onset cataracts. Cataracts occur at a much earlier age (usually between 30 and 40) than the general population, where females are usually affected more than men. We studied gender differences in cataract prevalence and treatment age in 243 DM1 patients (134 M; 109 F), aged 18 to 70 years, who were subsequently screened at routine follow-up. For each patient, information was collected on age, sex, CTG expansion, age of cataract onset, and age at cataract surgery, when available. Seventy-three patients, 30 females and 43 males, had cataracts, at a mean age of onset of 41.14 ± 12.64 in females, and 40.36 ± 10.03 in males. Sixty-nine of them underwent cataract surgery, males at an earlier age than females (42.8 ± 9.8 years versus 47.3 ± 12.6 years) and in 52.5% of cases before the age of 40, compared to 17.2% of females. The difference was statistically significant. The assumption that females in general and those with DM1 in particular develop cataracts more frequently and earlier than males is not confirmed, at least in this study. A possible explanation for these results could be related to non-advanced age, the protective role of estrogen and the lower prevalence of smoking in the study population.

Dental and maxillofacial manifestations of Steinert's myotonic dystrophy: A retrospective case series and therapeutic investigation.

This retrospective study was performed to analyse the facial features and occlusal anomalies in 18 patients with Steinert's myotonic dystrophy (MD1). Medical and surgical management issues noted in this study may contribute to clinical decision-making. This series included 18 patients with MD1 who presented for maxillofacial consultations. For all patients, the following characteristics were assessed: sex, age, intellectual ability, oral condition, initial assessment of the occlusion and facial aspect. In total, 11 of 18 patients underwent surgery (10 achieved occlusion modification, whereas one did not). amongst patients who underwent surgery and achieved occlusion modification, six had stable class I results and four had unstable results or exhibited a slight degradation. Facial muscles play an important role in craniomaxillofacial development and facial aspects. A high prevalence of malocclusions is present in patients with MD1. Orthodontics and orthognathic surgery can improve the quality of life for affected patients. However, the long-term results of these treatments may be disappointing, and relapse can occur in patients with the most severe disease. Aspects of disease to consider while planning for surgery include oral health, risks of instability and relapse, and risks involving anaesthesia.

Understanding the Perseverance of the Muscular Dystrophy Community One-Year into the COVID-19 Pandemic.

INTRODUCTION: In this study, we examined the long-term social and health impacts of the coronavirus disease 2019 (COVID-19) pandemic on people with muscular dystrophy. METHODS: We modified our prior COVID-19 Impact Survey to assess impacts from the continuing pandemic using feedback from muscular dystrophy experts, patients, and advocacy group/registry representatives. The survey assessed COVID-19 medical history, and the effects of the pandemic on social aspects, muscle disease, and medical care. We also used the validated 10-item Perceived Stress Scale. The de-identified, electronic survey was distributed to adults with muscular dystrophy via international patient registries and advocacy group websites from February 8, 2021 to March 22, 2021. RESULTS: Respondents (n = 1243 : 49% Facioscapulohumeral Muscular Dystrophy (FSHD); 43% Myotonic Dystrophy (DM), and 8% Limb-Girdle Muscular Dystrophy (LGMD)) were mostly women and middle-aged (range 18-90 years). Rates of COVID-19 infections were low at 8% with zero deaths. Reported recovery times were also short with only 9% reporting a recovery period greater than eight weeks, and 7% requiring hospitalization with one individual requiring a ventilator. Major challenges reported during the pandemic included stress management, particularly for those with LGMD (27%), and wearing a mask (24%). The majority reported a slight worsening of their disease state. Respondents reported moderate stress levels (stress score = 16.4; range = 0-39), with higher stress levels reported by women and those under age 30 years. Seventy-percent of participants who had telemedicine visits were satisfied with the encounters; however, most reported a preference for in-person visits. CONCLUSIONS: People with muscular dystrophy found ways to manage their stress and overcome obstacles during the COVID-19 pandemic. COVID-19 infection rates and medical complications were similar to a general population. Telemedicine visits may have a more permanent role in care.