Vaccination in Pediatric Hereditary and Genetic Neuromuscular disorders: Current Evidence-Based Recommendations

Abstract

Hereditary and genetic neuromuscular diseases include Duchenne and Becker Muscular Dystrophies (DMD and BMD), Spinal Muscular Atrophy (SMA), Charcot–Marie–Tooth disease (CMT), Congenital Myopathies (CM), Limb-Girdle Muscular Dystrophies (LGMD), Myotonic Dystrophy (DM1 and DM2), and other less common muscular dystrophies. In the last decade, management approaches have witnessed a paradigm shift towards potentially curative targeted, disease-modifying therapies. This narrative review collates information up to December 2025, outlines the clinico-epidemiological profile, recent therapeutic developments, and summarizes current recommendations relevant to pediatric immunization, with level and grade of evidence.  For DMD, newer therapeutic modalities include Exon skipping Antisense oligonucleotides (ASO) Eteplirsen, Golodirsen, Viltolarsen, and Casimersen, orally administered small molecule compound Ataluren, Adeno-associated virus-(AAV) mediated gene therapy Delandistrogene moxeparvovec, orally administered histone deacetylase inhibitor Givinostat, dissociative corticosteroid drug Vamorolone; and for SMA, ASO Nusinersen, AAV9 vector gene therapy Onasemnogene abeparvovec, and orally deliverable small molecule SMN2 RNA splicing modifier Risdiplam. Unlike DMD, where corticosteroids are the primary pharmacological treatment, the primary treatments for SMA are specific disease-modifying therapies. Corticosteroids and other immunosuppressants are used concomitantly with several disease modifying therapies. Only prednisone equivalent doses of ≥2 mg/kg body weight or ≥20 mg per day for weight >10 kg when administered for ≥14 consecutive days, are considered sufficiently immunosuppressive by the US Centers for Disease Control and Prevention (CDC) guidelines. In contrast, the Australian guidelines also consider both, a dose of <2 mg/kg per day for ≥14 days and ≥2 mg/kg per day for <14 days, to be immunosuppressive to preclude live vaccine administration during corticosteroid therapy. When indicated, gene therapy combined with corticosteroid therapy should be initiated a minimum 2-weeks after BCG vaccine administration. Live vaccine administration is recommended at least 4 weeks before or after administration of gene therapy with concomitant high dose corticosteroids. During gene therapy, all live vaccines are contraindicated, but not killed vaccines. Meningococcal conjugate vaccines are specifically recommended for patients with SMA, especially if thrombotic microangiopathy develops and eculizumab is used for treatment. The optimal (most immunogenic with least adverse events) route of vaccine administration in patients with neuromuscular disorders, despite significant muscle atrophy and muscle replacement by fat, is intramuscular, due to largely preserved vascularity.