Exon Publications, Brisbane, Australia
Spinal Muscular Atrophy (SMA) is a genetic condition that affects the nerves controlling muscle movement, leading to muscle weakness and progressive disability. This guide provides an in-depth yet accessible explanation of SMA, including its causes, symptoms, types, and the genetic mutations responsible for the condition. It explores diagnosis, treatment options such as new genetic therapies, and ways to manage the challenges of living with SMA. By offering comprehensive information in simple language, this article serves as a resource for patients, families, and caregivers seeking to understand and navigate this condition.
Keywords: Antisense oligonucleotide; Diagnosis of Spinal Muscular Atrophy; Epidemiology of Spinal Muscular Atrophy; Evrysdi; Genetics and Inheritance of Spinal Muscular Atrophy; Kugelberg-Welander disease; Living with Spinal Muscular Atrophy; Motor neurons; Neuromuscular disease; Nusinersen; Onasemnogene abeparvovec-xioi; Prognosis of Spinal Muscular Atrophy; Risdiplam; Risk Factors and Causes of Spinal Muscular Atrophy; SMN protein; SMN1 gene; SMN2 gene; Spinal injections; Spinraza; Survival motor neuron (SMN) protein; Symptoms of Spinal Muscular Atrophy; Treatment and Management of Spinal Muscular Atrophy; Type 1 SMA; Type 2 SMA; Type 3 SMA; Type 4 SMA; Types of Spinal Muscular Atrophy; Werdnig-Hoffmann disease; What is Spinal Muscular Atrophy; Zolgensma
Correspondence: Exon Publications, Brisbane, Australia. books@exonpublications.com
Cite as: Spinal Muscular Atrophy: Public Education. Brisbane (AU): Exon Publications; 2024. Published on 26 Nov.
Doi: https://doi.org/10.36255/https://doi.org/10.36255/spinal-muscular-atrophy-public-education
Copyright: Exon Publications.
License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 (CC BY-NC-ND 4.0) https://creativecommons.org/licenses/by-nc-nd/4.0/
Spinal Muscular Atrophy is a serious genetic disorder that affects the muscles used for movement, swallowing, and breathing. It is caused by a loss of specialized nerve cells, called motor neurons, in the spinal cord. These motor neurons are essential for communicating signals from the brain to muscles. Without these signals, muscles become weak and gradually shrink. SMA is a life-altering condition that not only impacts the individuals diagnosed with it but also their families and caregivers. This article aims to provide clear, accurate, and comprehensive information to help those affected by SMA better understand the condition, its challenges, and the available treatment and support options (1–3).
Spinal Muscular Atrophy is a genetic disorder that causes muscle weakness and affects a person’s ability to perform basic movements. The condition occurs when motor neurons, which are responsible for controlling voluntary muscles, are damaged or lost. These neurons are crucial for movement, as they send signals from the brain to the muscles. In SMA, the lack of functional motor neurons leads to progressive muscle weakness, making it difficult to walk, eat, or even breathe in severe cases. The severity of SMA varies widely, ranging from mild muscle weakness to life-threatening complications. The condition is classified as a neuromuscular disease because it primarily affects muscles and the nerves that control them.
Spinal Muscular Atrophy is a rare condition, affecting approximately 1 in 6,000 to 1 in 10,000 live births worldwide. It is one of the most common genetic causes of infant mortality. The condition occurs in people of all ethnic backgrounds and affects both males and females equally. About 1 in 40 to 1 in 60 individuals in the general population carries a genetic mutation in the SMN1 gene, which is responsible for SMA. Carrier screening and advances in newborn screening programs have improved early detection, enabling earlier interventions and better outcomes for those affected.
Spinal Muscular Atrophy is classified into several types based on the age at which symptoms begin and the severity of the condition. Type 1 SMA, also known as Werdnig-Hoffmann disease, is the most severe form and usually becomes evident within the first six months of life. Infants with this type have difficulty breathing and swallowing and often cannot sit without support. Type 2 SMA begins in childhood, typically between six months and 18 months of age. Children with Type 2 can sit without assistance but cannot stand or walk independently. Type 3 SMA, also called Kugelberg-Welander disease, usually appears after 18 months of age or in adolescence. Individuals with this type can walk independently for some time but may lose this ability as the condition progresses. Type 4 SMA is an adult-onset form, which is the mildest and least common. Symptoms develop after age 20 and primarily affect mobility, with minimal impact on life expectancy.
Spinal Muscular Atrophy is caused by mutations in the SMN1 gene, which provides instructions for producing a protein called survival motor neuron (SMN) protein. This protein is essential for the survival and function of motor neurons. In people with SMA, a mutation in the SMN1 gene leads to a deficiency of SMN protein, resulting in the loss of motor neurons and subsequent muscle weakness. SMA is inherited in an autosomal recessive pattern, meaning that an individual must inherit two faulty copies of the SMN1 gene, one from each parent, to develop the condition. People who inherit only one faulty copy are carriers and typically do not show symptoms. Another gene, SMN2, plays a role in the severity of the condition. While SMN2 also produces SMN protein, it does so less efficiently. The number of copies of the SMN2 gene can influence the severity of SMA, with more copies generally associated with milder symptoms.
The primary cause of Spinal Muscular Atrophy is a mutation in the SMN1 gene. This mutation leads to a deficiency in SMN protein, which is crucial for the health and survival of motor neurons. The main risk factor for SMA is having parents who are carriers of the SMN1 gene mutation. When both parents are carriers, there is a 25% chance with each pregnancy that their child will inherit two faulty copies of the gene and develop SMA. Other risk factors, such as family history, increase the likelihood of a child being born with the condition. However, SMA is not influenced by environmental or lifestyle factors, as it is purely genetic in origin.
The symptoms of Spinal Muscular Atrophy vary depending on the type and severity of the condition. In severe forms like Type 1 SMA, symptoms usually appear within the first six months of life and include floppy muscle tone, difficulty swallowing, and respiratory problems. Infants with Type 1 SMA may have trouble lifting their heads or moving their arms and legs. In milder forms like Type 2 or Type 3 SMA, symptoms may include delayed motor milestones, difficulty standing or walking, and progressive muscle weakness over time. Adults with Type 4 SMA may experience mild muscle weakness that develops gradually, affecting their ability to perform physical activities. Common symptoms across all types include muscle weakness, difficulty with mobility, and in severe cases, challenges with breathing and swallowing.
Diagnosing Spinal Muscular Atrophy involves a combination of clinical evaluations, genetic testing, and sometimes specialized tests to assess muscle and nerve function. A doctor may suspect SMA based on symptoms such as muscle weakness, developmental delays, or breathing difficulties. Genetic testing is the most definitive method for diagnosing SMA, as it can identify mutations in the SMN1 gene and determine the number of SMN2 copies. In some cases, electromyography (EMG) or muscle biopsies may be used to confirm the diagnosis by assessing the health of the muscles and motor neurons. Early diagnosis is crucial, as starting treatment early can significantly improve outcomes.
The treatment and management of Spinal Muscular Atrophy have advanced significantly in recent years. Several FDA-approved therapies target the genetic cause of SMA. Nusinersen (Spinraza) is an antisense oligonucleotide that increases the production of SMN protein by modifying the SMN2 gene. It is administered through spinal injections. Onasemnogene abeparvovec-xioi (Zolgensma) is a gene therapy that delivers a functional copy of the SMN1 gene to the body through a single intravenous dose. Risdiplam (Evrysdi) is an oral medication that also boosts SMN protein production by enhancing SMN2 gene activity. Supportive care plays a crucial role in managing symptoms and improving quality of life. This includes physical therapy to maintain mobility, respiratory support to manage breathing difficulties, and nutritional support for feeding challenges. Regular monitoring and a multidisciplinary approach are essential for addressing the complex needs of individuals with SMA.
The prognosis for individuals with Spinal Muscular Atrophy depends on the type and severity of the condition, as well as the timing of diagnosis and treatment. In the past, severe forms like Type 1 SMA were associated with significantly reduced life expectancy. However, advances in genetic therapies and supportive care have dramatically improved survival rates and quality of life for many individuals. Milder forms, such as Type 3 or Type 4 SMA, often have a near-normal life expectancy, though progressive muscle weakness may impact daily activities. Early intervention and access to modern treatments are key factors in improving outcomes for individuals with SMA.
Living with Spinal Muscular Atrophy involves adapting to the challenges of the condition while fostering a supportive and inclusive environment. Families play a central role in coordinating care and providing emotional support. Regular physical therapy can help maintain muscle strength and flexibility, while assistive devices such as wheelchairs or braces can enhance mobility and independence. Respiratory care, including non-invasive ventilation, may be needed for those with severe forms of SMA. Emotional support and mental health resources are also important for both individuals with SMA and their families. Advocacy and support groups can provide valuable resources, guidance, and a sense of community. Advances in treatment and early interventions offer hope for improved quality of life and greater independence for those living with SMA.
Spinal Muscular Atrophy is a challenging genetic condition, but advances in medical research and treatment have significantly improved the outlook for many individuals. Understanding its genetic causes, symptoms, and available therapies is crucial for managing the condition effectively.
This article was written by professional medical writers for the general public based on peer-reviewed articles indexed in PubMed and peer-reviewed for scientific accuracy by independent experts. It is intended solely for informational purposes and is not to be considered medical advice. The views and opinions expressed in this article are believed to be accurate at the time of publication, but the publisher, editors, or authors cannot be held responsible or liable for any errors, omissions, or consequences arising from the use of the information contained in this article. The publisher makes no warranties, implicit or explicit, regarding the contents of this article or its use.