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.

Concurrent nodular lymphocytic myositis and myasthenia gravis. A case report.

Localized painful nodules associated with focal myositis have been previously documented, either as isolated occurrences or in conjunction with systemic illnesses, such as polymyositis [1-4]. These nodules typically manifest over the course of 2-8 weeks and exhibit histological features consistent with inflammatory myositis. Here we present a unique case of a patient with a history of myasthenia gravis, who experienced exacerbation of myasthenic symptoms, accompanied by the development of palpable, tender nodules on her thighs and proximal weakness. Muscle biopsy revealed circumscribed mononuclear infiltrates predominantly composed of CD3+ and CD4+ lymphocytes. Furthermore, we detail the patient's rapid and sustained response to treatment with steroids (both intravenous pulse and maintenance therapy) and methotrexate. To the best of our knowledge, this represents the first documented case of nodular lymphocytic myositis concurrent with an exacerbation of myasthenia gravis, in a patient with no prior history of significant immunosuppression or chronic infection.

Evolving Therapeutic Options for the Treatment of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is the most common childhood form of muscular dystrophy. It is caused by mutations in the DMD gene, leading to reduced or absent expression of the dystrophin protein. Clinically, this results in loss of ambulation, cardiomyopathy, respiratory failure, and eventually death. In the past decades, the use of corticosteroids has slowed down the disease progression. More recently, the development of genetically mediated therapies has emerged as the most promising treatment for DMD. These strategies include exon skipping with antisense oligonucleotides, gene replacement therapy with adeno-associated virus, and gene editing with CRISPR (clustered regularly interspaced short palindromic repeats) technology. In this review, we highlight the most up-to-date therapeutic progresses in the field, with emphasis on past and recent experiences, as well as the latest clinical results of DMD micro-dystrophin gene therapy. Additionally, we discuss the lessons learned along the way and the challenges encountered, all of which have helped advance the field, with the potential to finally alleviate such a devastating disease.

Cancer and Myotonic Dystrophy.

Myotonic dystrophy (DM) is the most common muscular dystrophy in adults. Dominantly inherited CTG and CCTG repeat expansions in DMPK and CNBP genes cause DM type 1 (DM1) and 2 (DM2), respectively. These genetic defects lead to the abnormal splicing of different mRNA transcripts, which are thought to be responsible for the multiorgan involvement of these diseases. In ours and others' experience, cancer frequency in patients with DM appears to be higher than in the general population or non-DM muscular dystrophy cohorts. There are no specific guidelines regarding malignancy screening in these patients, and the general consensus is that they should undergo the same cancer screening as the general population. Here, we review the main studies that investigated cancer risk (and cancer type) in DM cohorts and those that researched potential molecular mechanisms accounting for DM carcinogenesis. We propose some evaluations to be considered as malignancy screening in patients with DM, and we discuss DM susceptibility to general anesthesia and sedatives, which are often needed for the management of cancer. This review underscores the importance of monitoring the adherence of patients with DM to malignancy screenings and the need to design studies that determine whether they would benefit from a more intensified cancer screening than the general population.

Seizure as Presenting Symptom of Multisystem Inflammatory Syndrome in Children.

We describe the case of a 13-year-old girl who presented with a new-onset seizure and fever and subsequently developed severe cardiac dysfunction, coronary artery dilation, and shock due to the surprising diagnosis of multisystem inflammatory syndrome in children (MIS-C). Although the clinical entity we now call MIS-C was first mentioned in the medical literature in April 2020, the full picture of this disease process is still evolving. Neurologic involvement has been described in cases with MIS-C; however, seizures are not a typical presenting symptom. Additionally, because children infected with SARS-CoV-2 are often asymptomatic, a documented preceding COVID-19 infection might not be available to raise suspicion of MIS-C early on. Febrile seizures, meningitis, and encephalitis are childhood illnesses that pediatricians are generally familiar with, but associating these clinical pictures with MIS-C is uncommon. Given the possibility of rapid clinical cardiogenic decline, as seen in our patient, a prompt diagnosis and appropriate monitoring and treatment are of utmost importance. This case report aims to raise awareness that new-onset seizures with fevers can be early or the first presenting symptoms in children with MIS-C, and further workup and close monitoring may be required.

Parent-of-Origin Effect on the Age at Symptom Onset in Myotonic Dystrophy Type 2.

Background and Objectives: The existence of clinical anticipation, congenital form, and parent-of-origin effect in myotonic dystrophy type 2 (DM2) remains uncertain. Here, we aimed at investigating whether there is a parent-of-origin effect on the age at the first DM2-related clinical manifestation. Methods: We identified patients with genetically confirmed DM2 with known parental inheritance from (1) the electronic medical records of our institutions and (2) a systematic review of the literature following the PRISMA 2020 guidelines and recorded their age at and type of first disease-related symptom. We also interrogated the Myotonic Dystrophy Foundation Family Registry (MDFFR) for patients with DM2 who completed a survey including questions about parental inheritance and age at the first medical problem which they related to their DM2 diagnosis. Results: A total of 26 patients with DM2 from 18 families were identified at our institutions as having maternal (n = 14) or paternal (n = 12) inheritance of the disease, whereas our systematic review of the literature rendered a total of 61 patients with DM2 from 41 families reported by 24 eligible articles as having maternal (n = 40) or paternal (n = 21) inheritance of the disease. Both cohorts were combined for downstream analyses. Up to 61% and 58% of patients had muscle-related symptoms as the first disease manifestation in maternally and paternally inherited DM2 subgroups, respectively. Four patients developed hypotonia at birth and/or delayed motor milestones early in life, and 7 had nonmuscular presentations (2 had cardiac events within the second decade of life and 5 had cataracts), all of them with maternal inheritance. A maternal inheritance was associated with an earlier (within the first 3 decades of life) age at symptom onset relative to a paternal inheritance in this combined cohort, and this association was independent of the patient's sex (OR [95% CI] = 4.245 [1.429-13.820], p = 0.0117). However, this association was not observed in the MDFFR DM2 cohort (n = 127), possibly because age at onset was self-reported, and the information about the type of first symptom or medical problem that patients related to DM2 was lacking. Discussion: A maternal inheritance may increase the risk of an early DM2 onset and of cataracts and cardiovascular events as first DM2 manifestations.

Intravenous immunoglobulins in an adult case of post-EBV cerebellitis.

Post-Epstein-Barr virus (EBV) cerebellitis is very rare complication of infectious mononucleosis and only a few adult cases are reported in literature. We present a 23-year-old patient who was admitted to the neurology service with worsening ataxia, nystagmus and dysarthria, 1 week after infectious mononucleosis. Imaging and cerebrospinal fluid studies were normal, serum studies revealed acute transaminitis and positive EBV viral capsid IgM and IgG. The patient underwent a 5-day course of intravenous immunoglobulins with rapid resolution of all his symptoms and was safely discharged home. The pathophysiology of post-EBV cerebellitis involves autoreactive antibodies, rather than a direct viral insult. Antineuronal antibodies might be the result of a mimicry between EBV proteins and neuronal antigens or they can be secreted by the EBV-transformed lymphocytes themselves. Many reports stress the benign, self-limiting nature of this syndrome; however, immunotherapy might de facto decrease the severity and duration of illness.