Neuromuscular Disorders | Genetic Testing
Genetic testing can improve care for people with neuromuscular diseases
Navigating neuromuscular diagnoses with genetic testing may lead to better treatment
Genetic testing can bridge the gap between uncertainty and informed proactive care in neuromuscular disorders, where every moment counts. This shift in approach is transformative, offering new hope and possibilities.
By finding a genetic basis for the neuromuscular disorder, healthcare providers may be able to do more than alleviate symptoms. They can consider interventions to help target the underlying cause.
Neuromuscular disorders like Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA) have a known genetic cause, and genetic testing can be a critical step on the path to treatment.
Genetic testing makes it easier for patients with neuromuscular disease to seek more opportunities for precise management of their condition and avoid unnecessary treatments and delays.
Genetic testing can also prove important for the relatives of people with neuromuscular disorders by supplying vital knowledge about family genetics.
Genetics and Duchenne muscular dystrophy
A change to the gene that produces dystrophin, a protein essential for maintaining healthy muscle cells, causes Duchenne muscular dystrophy.¹ When muscles don’t have enough dystrophin, they become fragile. Muscle weakness can begin as early as age 2 or 3, starting a lifelong need for precise information to help aid treatment planning.²
The condition first affects the core muscles. Over time, muscle weakness extends to the body’s extremities. As children with DMD grow to adulthood, their cardiac and respiratory muscles degenerate, which can lead to acute respiratory failure, cardiomyopathy and heart arrhythmias.²
Until recently, children with DMD did not usually survive beyond the age of 20. With recent developments in cardiac and respiratory care, life expectancies are growing longer. More people with DMD live into their early 30s than ever, going to college, having careers and starting families.²
Males* are born with one X and one Y chromosome, and females† are born with two X chromosomes. DMD primarily affects boys because if their X chromosome has a defect in the dystrophin gene, boys do not have another X chromosome to counteract the defect’s consequences. For girls, if one X chromosome has the defect, they may have DMD symptoms of variable severity or be at risk for heart complications.³
The condition arises from a new genetic variant in about one-third of DMD cases. But in most cases–about two-thirds–the mother has a dystrophin defect in one of her X chromosomes. When a mother carries the DMD gene, half of her sons are expected to have the variant and half of her daughters are expected to be carriers.⁴
These numbers are one of many reasons that genetic testing for neuromuscular disorders may have important implications for families who carry the DMD gene.
The genetic counseling that should accompany genetic testing can support family planning decisions, aid discussions around prenatal diagnosis and support early diagnosis of asymptomatic family members. For providers, genetic testing is another tool in their toolkit to support recommendations for managing and treating conditions like Duchenne.⁵_ ⁸
Genetic testing for neuromuscular conditions: Hope for patients
Genetic testing for neuromuscular disorders like Duchenne muscular dystrophy represents hope for affected individuals and their families. Knowing a person’s genetic makeup can help unveil underlying causes, allowing for a definitive diagnosis to provide clarity and direction. Swift medical management can work to improve the quality of life for patients and potentially slow disease progression.
Typical management for DMD, like physical therapy and glucocorticoids, helps relieve symptoms and slow muscle deterioration. Emerging gene therapies are designed to slow disease progression even more.⁹
For example, about 80% of DMD variants are amenable to exon-skipping therapies, which help cells bypass the damaged part of the DMD gene to produce a form of dystrophin.¹⁰ A genetic test can help determine if a patient is eligible for exon-skipping therapy.⁸
Duchenne is just one example of a genetic neuromuscular disease. Genetic testing can help inform the management of other neuromuscular conditions with a genetic cause, including:
- Becker muscular dystrophy (BMD), a milder form of muscular dystrophy that, like Duchenne, is caused by alterations in the dystrophin gene
- Spinal muscular atrophy (SMA), a disorder that affects motor neurons
- Pompe disease (PD), a disorder where complex sugars build up in the body’s cells and cause muscle weakness and wasting
Sometimes, when a provider suspects a possible DMD diagnosis, genetic testing reveals a different answer. Sometimes, the true diagnosis relates to other neuromuscular disorders, like SMA. Comprehensive genetic testing can be crucial to catching these differences quickly and early and delivering the right care to the right patients.¹¹
More than 6% of individuals whose referring physician diagnosed a recognizable neuromuscular disorder like DMD or SMA based on clinical features alone had multi-gene panel testing that revealed a diagnosis related to a different gene.¹¹ Had the clinician only tested for the DMD or SMA gene, they may have missed this crucial information.
Prognostic insights: Clearing the path forward
Genetic testing helps inform a diagnosis and may offer a glimpse into the future. Prognostic insights from genetic results can support long-term care planning and provide patients and their families with a clearer outlook. Understanding the trajectory of the disorder allows for more informed decisions regarding treatment, lifestyle adjustments and support systems.
Prognostic information can help individuals with neuromuscular disorders take an active role in their care, fostering a sense of agency and control. Together, families can navigate the complexities of neuromuscular disorders and move forward with collective purpose and determination.
Prognostic information also helps equip healthcare providers with the knowledge to provide compassionate, comprehensive care that addresses immediate needs and long-term considerations.⁸
Other benefits of genetic testing for neuromuscular conditions
Without genetic testing, arriving at an accurate diagnosis of a neuromuscular condition can be akin to navigating through a labyrinth blindfolded. It often involves a series of trial and error, subjecting patients to tests and evaluations and prolonging the diagnostic journey.
The cost of these tests and assessments can be high over time. Genetic testing can be more cost-effective because it may speed up the diagnostic process, helping patients receive appropriate treatments faster.⁸
Genetic testing can also create important opportunities that patients might not otherwise be able to access. For example, definitive genetic answers help enable patients to participate in clinical trials, which might give them access to developing therapies. Patient registries, essential tools for understanding the full impacts of neuromuscular diseases, usually allow people to participate in these trials only when they have a confirmed genetic diagnosis.⁸
In addition to possible medical benefits, there can be social ones, too: a genetic diagnosis can help connect patients. When navigating a serious condition, finding a community of people who understand this experience can be an essential source of support.⁸
Neuromuscular disorders can be hereditary, so families need a comprehensive understanding of how neuromuscular conditions might recur in future generations. Genetic testing may provide clarity, enabling families to make informed decisions about family planning and seek appropriate support.⁸
Comprehensive genetic testing vs. focused panels for testing neuromuscular conditions: What are the benefits?
Comprehensive genetic testing casts a wide net, analyzing various genes associated with neuromuscular disorders. This breadth of coverage can mean it’s more likely to identify rare or less common gene variants that focused panels might miss. This depth of information can help facilitate an accurate diagnosis and guide tailored treatment plans.
Broad panel testing increases efficiency by evaluating multiple potential genes simultaneously. This streamlined approach reduces the need for sequential testing, which can be time-consuming and may increase costs and lead to diagnostic delays.
Imagine a library of genetic information, each book representing a potential genetic variant associated with neuromuscular disorders. Comprehensive testing allows us to scan multiple books simultaneously, uncovering many possibilities. This efficiency supports a fast and accurate diagnosis.
Realizing the potential benefits of genetic testing
Genetic testing for neuromuscular disorders like DMD may be a game-changer. Genetic information can help healthcare providers tailor treatment to each individual, working to enhance well-being and quality of life. Prognostic insights may provide a roadmap for long-term care planning, offering patients and their families a clearer outlook on the future.
Personalized care becomes more than just a buzzword; it becomes a reality tailored to each individual’s unique genetic makeup. This level of precision is a testament to the strides we’ve made in understanding and harnessing the power of genetics to help patients and their families navigate their health.
Invitae offers a comprehensive panel for neuromuscular disorders that simultaneously tests up to 230 genes associated with hereditary neuromuscular conditions.
To learn more about genetic testing, visit Invitae’s website.
* assigned male at birth
†assigned female at birth
- Positive results guide: DMD. Invitae. Accessed November 16, 2023.
- Duchenne muscular dystrophy (DMD). Muscular Dystrophy Association. Accessed December 14, 2023.
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- Duchenne & Becker muscular dystrophy. Osmosis from Elsevier. August 11, 2016. Accessed December 14, 2023.
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- Tawil R, et al. Neurology. 2015;85(4):357–364.
- Kang PB, et al. Neurology. 2015;84(13):1369–1378.
- Kassardjian CD, et al. Muscle Nerve. 2016;54(6):1007–1009.
- Patterson G, et al. Eur J Pharmacol. 2023;15(947):175675.
- Datta N, Ghosh PS. Curr Neurol Neurosci Rep. 2020;20(6):14.
- Winder T, et al. Neurol Genet. 2020;6(2):e412.
