Walker-Warburg syndrome

Walker-Warburg Syndrome (WWS) is a rare form of autosomal recessive congenital muscular dystrophy associated with brain and eye abnormalities. WWS has a worldwide distribution. The overall incidence is unknown but a survey in North-eastern Italy has reported an incidence rate of 1.2 per 100,000 live births. It is the most severe form of congenital muscular dystrophy with most children dying before the age of three years. WWS presents at birth with generalized hypotonia, muscle weakness, developmental delay with mental retardation and occasional seizures. It is associated with type II cobblestone lissencephaly, hydrocephalus, cerebellar malformations, eye abnormalities and congenital muscular dystrophy characterized by hypoglycosylation of α-dystroglycan. Several genes have been implicated in the etiology of WWS, and others are as yet unknown. Several mutations were found in the Protein O-Mannosyltransferase 1 and 2 (POMT1 and POMT2) genes, and one mutation was found in each of the fukutin and fukutin-related protein (FKRP) genes. Laboratory investigations usually show elevated creatine kinase, myopathic/dystrophic muscle pathology and altered α-dystroglycan. Antenatal diagnosis is possible in families with known mutations. Prenatal ultrasound may be helpful for diagnosis in families where the molecular defect is unknown. No specific treatment is available. Management is only supportive and preventive

A National Spinal Muscular Atrophy Registry for Real-World Evidence.

BACKGROUND: Spinal muscular atrophy (SMA) is a devastating rare disease that affects individuals regardless of ethnicity, gender, and age. The first-approved disease-modifying therapy for SMA, nusinursen, was approved by Health Canada, as well as by American and European regulatory agencies following positive clinical trial outcomes. The trials were conducted in a narrow pediatric population defined by age, severity, and genotype. Broad approval of therapy necessitates close follow-up of potential rare adverse events and effectiveness in the larger real-world population. METHODS: The Canadian Neuromuscular Disease Registry (CNDR) undertook an iterative multi-stakeholder process to expand the existing SMA dataset to capture items relevant to patient outcomes in a post-marketing environment. The CNDR SMA expanded registry is a longitudinal, prospective, observational study of patients with SMA in Canada designed to evaluate the safety and effectiveness of novel therapies and provide practical information unattainable in trials. RESULTS: The consensus expanded dataset includes items that address therapy effectiveness and safety and is collected in a multicenter, prospective, observational study, including SMA patients regardless of therapeutic status. The expanded dataset is aligned with global datasets to facilitate collaboration. Additionally, consensus dataset development aimed to standardize appropriate outcome measures across the network and broader Canadian community. Prospective outcome studies, data use, and analyses are independent of the funding partner. CONCLUSION: Prospective outcome data collected will provide results on safety and effectiveness in a post-therapy approval era. These data are essential to inform improvements in care and access to therapy for all SMA patients

Autoimmune Neuromuscular Disorders in Childhood

Autoimmune neuromuscular disorders in childhood include Guillain-Barré syndrome and its variants, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), juvenile myasthenia gravis (JMG), and juvenile dermatomyositis (JDM), along with other disorders rarely seen in childhood. In general, these diseases have not been studied as extensively as they have been in adults. Thus, treatment protocols for these diseases in pediatrics are often based on adult practice, but despite the similarities in disease processes, the most widely used treatments have different effects in children. For example, some of the side effects of chronic steroid use, including linear growth deceleration, bone demineralization, and chronic weight issues, are more consequential in children than in adults. Although steroids remain a cornerstone of therapy in JDM and are useful in many cases of CIDP and JMG, other immunomodulatory therapies with similar efficacy may be used more frequently in some children to avoid these long-term sequelae. Steroids are less expensive than most other therapies, but chronic steroid therapy in childhood may lead to significant and costly medical complications. Another example is plasma exchange. This treatment modality presents challenges in pediatrics, as younger children require central venous access for this therapy. However, in older children and adolescents, plasma exchange is often feasible via peripheral venous access, making this treatment more accessible than might be expected in this age group. Intravenous immunoglobulin also is beneficial in several of these disorders, but its high cost may present barriers to its use in the future. Newer steroid-sparing immunomodulatory agents, such as azathioprine, tacrolimus, mycophenolate mofetil, and rituximab, have not been studied extensively in children. They show promising results from case reports and retrospective cohort studies, but there is a need for comparative studies looking at their relative efficacy, tolerability, and long-term adverse effects (including secondary malignancy) in children