“It is truly remarkable how quickly the field has advanced in spinal muscular atrophy (SMA), from the mapping and cloning of the causative survival motor neuron 1 gene(SMN1) in the early 1990s to the advent of gene-augmenting and replacement therapies less than 30 years later,” Yeo and Darras wrote in Pediatric Neurology. 

Indeed, the dizzying pace at which landmark discoveries and therapeutic advancements have been made over the last few decades in the field of neurodegenerative disorders is a testament to the power of science and the unwavering diligence of the scientists at the helm of this important work. 

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Clinicians have long known that clinical phenotype correlates inversely with the number of SMN2 copies that a patient possesses. The consensus was that there were 5 clinical phenotypes, ranging from mild to severe, based on the age of onset, motor milestones achieved, and functional status. 

Clinical Characteristics of SMA 

Because muscular dysfunction is such a key characteristic of the disease and the main contributor to disease burden, clinicians have focused their attention on developing therapeutics to improve motor function. The most successful of these efforts is the drug nusinersen, which was approved by the US Food and Drug Administration in 2016. 

Studies indicate that nusinersen can result in modest motor function improvement over time; patients may also experience improvements in fatigue and exercise tolerance. Currently, all patients, regardless of age or body weight, are prescribed nusinersen 12 mg every 6 months. Because this drug has only been in use for the last few years, long-term clinical data remains unavailable, raising several important questions, such as the best monitoring methods and whether nusinersen therapy can be individualized. 

Aside from muscular dysfunction, it is worth noting that SMA is a multisystemic disorder, affecting the heart in the form of atrial/ventricular septal defects, the liver by way of elevated triglycerides and dyslipidemia resembling nonalcoholic fatty liver disease, the bones and joints as osteopenia, and the kidney in the form of nephrocalcinosis). Therefore, it is standard practice for patients to undergo regular follow-up visits to ensure that any newly diagnosed pathology in any part of the body is promptly dealt with. 

Factoring in the Patient Perspective 

So, we now have a good grasp on the genetics of SMA (with regards to SMN1), its manifestations (both muscular and multisystemic), the therapies available (such as nusinersen) and the ones under development (such as gene therapy). What else are we missing? 

In the Journal of Neuromuscular Diseases, Slayter and colleagues argued that there is “a need to study additional under-recognized health domains such as quality of life, fatigue, bulbar function, respiratory function, and independence.” 

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Slayter and colleagues asserted that the primary paradigm of which we view SMA is that it is a neurodegenerative disorder. And because the disease progression is so visible (in terms of ambulatory ability), physicians can sometimes be overtly focused on the muscular aspects of the disease at the expense of intangible features that may matter equally to patients with this disorder. 

it is therefore vital that physicians take the time to understand how a disease impacts the patient experience. In recent years, there has been a growing movement to let patients do the talking: hence, the proliferation of patient-reported outcome measures (PROMs) and studies involving semistructured interviews with affected individuals. 

Slayter and colleagues conducted a scoping review and network visualization to characterize currently existing PROMs that have been used in adult patients with SMA. Their goal is to highlight areas of need in which more research is required. 

From the very onset, the authors of this study proposed that limited clinician exposure to PROMs is a significant reason why they are absent in so many consultations. There is a sort of mindset among some medical circles that regard the main task of a physician as one to treat physical symptoms, of which, if successful, will naturally result in emotional/mental well-being. The problem with this way of thinking is that disease phenotype does not neatly translate into degree of disease burden; some patients may have relatively light muscular dysfunction but feel unable to cope emotionally or socially. 

If the ultimate goal is to maximize a patient’s well-being, physicians need to understand that both physical and mental/emotional needs should be met: hence, the relevance of PROMs in medicine today. 

Slayter and colleagues reported that a number of often overlooked domains remain highly relevant in SMA: mental health and cognition, communication and speech, pain, and fatigue. In addition, studies indicate sexual function and systemic issues also rank high in importance among patients with SMA. To encourage patients to give a fuller account about their experiences with SMA, PROMs should cover all these issues. 

The number of SMA-specific PROMs is growing, indicating a shift in clinical mindset. Newly developed PROMs are more likely to include difficult discussions on the impact of the disease on one’s sense of self, confidence, and how one views the future. These newly developed PROMs may soon one day displace what Slayter and colleagues term the “current patchwork quilt of validation and utilization.” 

There is no doubt that the task of monitoring and managing a patient with SMA requires both expertise and empathy, encompassing both objective and subjective realities. The question worth pondering is whether a combination of better SMA therapeutics and a more refined focus towards PROMs can offer us a vision for the future better than the one we currently have. For many of the individuals struggling with both external and internal needs in the daily fight against SMA, the answer is likely to be a resounding yes. 


Yeo CJJ, Darras BT. Overturning the paradigm of spinal muscular atrophy as just a motor neuron diseasePediatr Neurol. Published online January 20, 2020. doi:10.1016/j.pediatrneurol.2020.01.003

Slayter J, Casey L, O’Connell C. Patient reported outcome measures in adult spinal muscular atrophy: a scoping review and graphical visualization of the evidenceJ Neuromuscul Dis. Published online March 7, 2023. doi:10.3233/JND-221595