Understanding Congenital
Myasthenic Syndromes: Rare, Complex, and Underserved

Congenital Myasthenic Syndromes (CMS) are a clinically and genetically heterogeneous group of congenital disorders that typically present with muscle weakness in the first decade of life but often remain undiagnosed for prolonged periods or are misdiagnosed. Published estimates of CMS prevalence in the global population support that CMS are a group of ultrarare diseases. The reported CMS global prevalence is approximately 5 per one million for all genotypes.^1-7 argenx is committed to advancing scientific understanding in rare muscular diseases, bringing scientific innovation to a community that has been long underserved.

The Biology and Burden of CMS

CMS are caused by various gene mutations involving the neuromuscular junction, the place where nerve and  muscle cells meet.^8,9 When this process is disrupted, muscles cannot respond reliably, resulting in weakness and other symptoms that worsen.⁸

For people living with CMS, the impact can be broad and deeply disruptive, affecting muscle strength, mobility,  endurance, breathing, and the ability to participate in everyday life.^8,9 Because CMS can be caused by mutations in more than 30 different genes, symptoms and severity can vary widely from one person to the next.¹⁰ CMS most commonly affects muscles in the arms and legs, but it can also involve muscles of the face, eyes and eyelids, as well as those used for chewing, swallowing, speaking, and breathing.⁸ In practice, this can mean difficulty walking or climbing stairs, limited endurance, problems with feeding or swallowing, speech challenges, or respiratory complications.^8,9 Children with more severe forms may experience delayed milestones, feeding difficulties, and breathing problems from infancy onward, with some requiring feeding tubes or breathing support.⁸ The earlier the onset, the more severe its impact is likely to be.¹⁰

The Diagnostic Gap and Its Consequences

Reaching a correct diagnosis is one of the greatest challenges in CMS. Its resemblance to autoimmune myasthenic conditions, most commonly seronegative myasthenia gravis, means many patients are misdiagnosed before a genetic workup confirms the true cause.¹¹ Because the underlying mechanism differs across subtypes, what helps one patient may not work for another, making genetic precision a clinical imperative.¹¹

Our Commitment to the CMS Community

Our commitment to the CMS community is rooted in a deep understanding of the complexity and unmet need in this rare neuromuscular disease. We focus our research on specific CMS subtypes where the underlying biology is still emerging, aiming to generate.

That focus has taken shape through two parallel efforts: our natural history study, designed to better understand the CMS patient journey and disease burden, and our Phase 1b clinical trial of adimanebart in patients with CMS. Together, these programs represent argenx’s commitment to understanding CMS and advancing research that may benefit patients living with CMS.

Adimanebart was developed through argenx’s Immunology Innovation Program (IIP), which continues to translate breakthrough immunology insights into differentiated antibody-based medicines. The program bridges our  expertise in MuSK biology with our antibody engineering and clinical development capabilities to advance neuromuscular disease treatment. The program recently had its first proof of concept read out in patients living with CMS, currently active in spinal muscular atrophy, and will explore other indications in the future, with the aim of a wide range of patients.