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Medical Genetics 101: Neuromuscular Diseases


This 101 course will explore various aspects of medical genetics, including an introduction to the field, different types of genetic disorders, and specific diseases affecting different body systems. The understanding of genetics plays a crucial role in diagnosing, managing, and treating genetic disorders, ultimately improving the lives of individuals and families affected by these conditions. In the course each article will focus on a specific category of disorders, providing an overview of the genetic basis, clinical manifestations, diagnostic approaches, and available treatment for different diseases and diso.rders

This series will be divided into eight articles:

  1. Medical Genetics 101: Introduction to Medical Genetics

  2. Medical Genetics 101: Chromosomal Aberrations

  3. Medical Genetics 101: Neuromuscular Diseases

  4. Medical Genetics 101: Mental and Behavioral Diseases

  5. Medical Genetics 101: Central Nervous System Diseases

  6. Medical Genetics 101: Hematological Diseases

  7. Medical Genetics 101: Metabolic Diseases

  8. Medical Genetics 101: Skeletal and Connective Tissue Diseases

Medical Genetics 101: Neuromuscular Diseases

Neuromuscular diseases are a group of disorders that strike at the intersection of the nervous system and the muscular system. These conditions encompass a wide spectrum of disorders, each characterized by specific mutations that disrupt the intricate harmony between nerves and muscles. Their impact is profound, often exacting physical, emotional, and social tolls on individuals and their families. Understanding the complexities of the genetics of neuromuscular diseases is not only crucial for those directly affected but also for the broader medical community and society as a whole. Many genetic mutations disrupt the normal function of proteins critical for muscle contraction, nerve signalling, or both. The effects are wide-ranging, from muscle weakness and atrophy to sensory impairments, respiratory distress, and even cognitive challenges. This article embarks on a comprehensive review of the world of neuromuscular genetic diseases by giving a closer look at some of the most common neuromuscular genetic diseases, shedding light on their clinical manifestations, their associated genetic mutations, their diagnosis and the challenges they pose to those affected.

Types of Neuromuscular Genetic Diseases

Diagnosing neuromuscular genetic diseases is a complex and intricate process, usually necessitating a multifaceted approach that integrates clinical evaluation, genetic testing, and specialized diagnostic procedures. These diseases constitute a diverse spectrum of conditions, each presenting distinct clinical features and underlying genetic causes. One of the foundational steps in the diagnostic process involves gathering a comprehensive medical history. This encompasses a detailed account of the patient's symptoms, their onset, progression, and any patterns observed. Additionally, understanding the family's medical history is crucial, as many neuromuscular genetic diseases have a hereditary component. A comprehensive physical examination is also conducted to assess muscle strength, tone, reflexes, coordination, and sensory function. Specific clinical features such as muscle wasting, contractures, or gait abnormalities, can provide important clues about the underlying neuromuscular disorder.

Electromyography (EMG) is a key diagnostic tool for neuromuscular disorders (Rubin, 2019) [Figure 1]. It involves the insertion of small electrodes into muscles to record electrical activity. EMG can help differentiate between nerve and muscle problems and assess the severity of nerve or muscle dysfunction [Figure 1]. Nerve conduction studies (NCS) measure the speed and strength of electrical signals as they travel along nerves (Tavee, 2019). Abnormal results can indicate peripheral nerve damage or dysfunction. In some cases, a small sample of muscle tissue is collected through a surgical procedure and examined under a microscope. Muscle biopsies can reveal specific abnormalities that may aid in diagnoses, such as muscle fibre atrophy, inflammation, or the presence of abnormal protein aggregates (Nix & Moore, 2020). Magnetic resonance imaging (MRI) scans can provide detailed images of muscle and nerve structures. They are particularly useful for assessing muscle wasting and detecting any structural abnormalities (Glover, 2011). Ultrasound imaging can assess peripheral nerves for signs of enlargement, compression, or other abnormalities (Aldrich, 2007). Blood tests can measure the levels of certain enzymes, such as creatine kinase (CK), which can be elevated in conditions such as muscular dystrophy (Eng et al., 1990).

Figure 1: Electromyography (EMG) evaluates the health and function of skeletal muscles and the nerves that control them (Cleveland Clinic, 2023).

Genetic testing is a crucial component of diagnosing neuromuscular genetic diseases. This involves analyzing a patient's DNA to identify specific genetic mutations associated with the suspected disorder. Different genetic tests are available, including targeted gene sequencing, whole exome sequencing, and whole genome sequencing, depending on the specific condition being investigated. For conditions caused by repeat expansion mutations (e.g., myotonic dystrophy, Friedreich's ataxia), specialized tests are performed to measure the size of the repetitive DNA sequences within the associated genes (Massey et al., 2018).

Muscular Dystrophy

Muscular dystrophy is a complex and diverse group of genetic disorders characterized by progressive muscle weakening that, as it is a progressive condition, worsens over time [Figure 2]. As the muscles weaken and degenerate, individuals with muscular dystrophy often experience increasing difficulty with tasks that require muscle strength and endurance. These disorders primarily affect the muscles responsible for movement and can lead to a wide range of symptoms. Muscular dystrophy is caused by mutations in genes that are essential for the structure and function of muscle fibres (Pandey et al., 2015).

Figure 2: Muscular dystrophy is a complex and diverse group of genetic disorders characterized by progressive muscle weakening that worsens over time (Research Outreach, n.d.).

Common symptoms of muscular dystrophy include muscle weakness, difficulty with mobility and coordination, muscle cramps, and muscle contractures (abnormal shortening of muscles or tendons). The age of onset and the rate of disease progression can vary widely among different types of muscular dystrophy. While there is no cure for muscular dystrophy, various management strategies can help improve quality of life (Janas, 1996). These may include physical therapy, mobility aids (e.g., wheelchairs or braces), assistive devices, and medications to manage symptoms and delay disease progression. In recent years, gene therapy and other innovative approaches have shown promise for treating some forms of muscular dystrophy. Ongoing research and advancements in medical science continue to offer hope for improved treatments and therapies for individuals living with muscular dystrophy.

Diagnosis for muscular dystrophy typically involves a combination of clinical evaluation, genetic testing, muscle biopsy, and electromyography (EMG) to assess muscle function and identify the specific type of muscular dystrophy. There are several different types of muscular dystrophy, each caused by mutations in specific genes. Progression and prognosis can vary widely depending on the type and genetic mutations involved.

Figure 3: Dystrophin is crucial in facilitating the transmission of muscle contraction force from within the muscle cell to the cell membrane (Muscular Dystrophy Association, n.d.).

Duchenne muscular dystrophy (DMD) stands out as one of the prevalent and gravest forms of muscular dystrophy, typically manifesting symptoms in early childhood. By their teenage years, affected individuals often experience a loss of ambulation (the ability to walk without the need for assistance) (Duan et al., 2021). This genetic disorder predominantly affects males and is primarily attributed to mutations in the dystrophin gene, leading to a deficiency of the critical protein dystrophin. The most common cause of DMD involves substantial deletions of one or more exons in the dystrophin gene, which disrupts the gene's reading frame, resulting in the production of an impaired, truncated dystrophin protein. These mutations culminate in the marked reduction or complete absence of functional dystrophin in muscle cells. Typically, dystrophin is crucial in facilitating the transmission of muscle contraction force from within the muscle cell to the cell membrane, spanning the muscle cell's core to its periphery due to its considerable length [Figure 3]. In the absence of dystrophin, muscle fibres become highly susceptible to damage during muscle contractions, ultimately leading to progressive muscle degeneration (Fortunato et al., 2021). On the other hand, Becker muscular dystrophy (BMD) represents a less severe form of muscular dystrophy, also stemming from mutations in the dystrophin gene. Symptoms in BMD closely resemble those of DMD, yet they tend to progress at a slower pace and exhibit milder severity (Flanigan, 2014). DMD and BMD are inherited in an X-linked recessive manner, given that the dystrophin gene is located on the X chromosome.

Facioscapulohumeral muscular dystrophy (FSHD) affects the muscles of the face, shoulders, and upper arms. It is characterized by muscle weakness and atrophy in these areas (Tawil, 2018). FSHD is caused by mutations in the DUX4 gene. The DUX4 gene encodes a transcription factor called DUX4 (Double Homeobox 4). Transcription factors are proteins that control the expression of other genes by binding to specific DNA sequences and regulating their activity. The typical mutation found in DUX4 is a reduction of a repetitive DNA sequence called the D4Z4 repeat on chromosome 4. This reduction results in the inappropriate activation of the DUX4 gene in muscle cells, which is believed to be associated with the activation of pathways that can lead to cell damage, such as inhibition of myogenic differentiation, inflammation, oxidative stress and DNA damage, impaired transcript quality control, protein aggregation and apoptosis (Mocciaro et al., 2021) [Figure 4].

Figure 4: Physiological and pathological roles of DUX4 (Mocciaro, 2021).

Myotonic dystrophy (DM) is a group of genetic neuromuscular disorders characterized by muscle weakness and myotonia, which is a prolonged involuntary muscle contraction followed by delayed muscle relaxation that can lead to difficulties in releasing a handshake or letting go of objects. Myotonic dystrophy is one of the most common forms of muscular dystrophy in adults and is divided into two main types: myotonic dystrophy type 1 (DM1) and myotonic dystrophy type 2 (DM2), each associated with specific genetic mutations (Turner & Hilton-Jones, 2014). DM1, also known as Steinert's disease, is the more common and better-known form of myotonic dystrophy. It is primarily caused by an expanded CTG repeat sequence in the dystrophia myotonica protein kinase (DMPK) gene located on chromosome 19 (Kaliman & Llagostera, 2008).

Individuals with DM1 experience progressive muscle weakness, particularly in the face, neck, hands, and lower extremities. This weakness can affect activities such as grasping objects and swallowing. DM1 is a multi-system disorder, affecting not only muscles but also other organs such as the heart, eyes, and endocrine system where cardiac abnormalities, cataracts, and hormone imbalances can occur [Figure 5]. DM2, also known as proximal myotonic myopathy (PROMM), is caused by an expanded CCTG repeat sequence in the CCHC-type zinc finger nucleic acid-binding protein (CNBP) gene located on chromosome 3 (Meola, 2020). Similar to DM1, DM2 is also characterized by muscle weakness, particularly in the proximal muscles of the hips and shoulders. Myotonia in DM2 is milder than in DM1 but it can still cause muscle stiffness and delayed muscle relaxation. DM2 can also affect multiple organ systems, including the heart, eyes, and endocrine system. However, DM2 typically has a later age of onset compared to DM1, often appearing during adulthood.

Figure 5: Symptoms of the myotonic dystrophy (Very Well Health, n.d.).

Spinal Muscular Atrophy (SMA)

Spinal muscular atrophy (SMA) is a group of inherited neuromuscular disorders characterized by the degeneration of motor neurons in the spinal cord and the lower brainstem (Kolb and Kissel, 2015). These vital motor neurons act as messengers, transmitting crucial signals from the brain to the muscles and facilitating voluntary muscle movement. The progressive degeneration of these motor neurons is at the core of SMA pathology, resulting in a gradual and relentless weakening and wasting of muscles [Figure 6]. SMA is a condition that manifests in various forms, each distinguished by the age of onset and the severity of symptoms.

Figure 6: The degeneration of motor neurons leads to atrophy (Together in SMA, n.d.).

Type 1Werdnig-Hoffmann diseaseis the most severe form and typically manifests in infancy. Babies with type 1 SMA have profound muscle weakness and difficulty breathing, swallowing, and moving. Without intervention, this disease can be life-threatening (Audic and Barnerias, 2020). Type 2 usually shows symptoms in early childhood; children with type 2 SMA have moderate to severe muscle weakness, and while they may never achieve the ability to walk independently, they can often sit without support (Wadman et al., 2020). Type 3 (Kugelberg-Welander disease) generally begins in late childhood or adolescence. This one is milder than the earlier-onset types, and affected individuals may retain the ability to walk, although they might experience muscle weakness and mobility issues (Salort-Campana and Quijano-Roy, 2020). Type 4 is the adult-onset form of SMA. It is the mildest form, characterized by mild muscle weakness and a slow progression of symptoms (D’Amico et al., 2011).

SMA is primarily caused by mutations in the survival motor neuron 1 (SMN1) gene. The SMN1 gene encodes the survival motor neuron (SMN) protein, which plays a critical role in motor neuron function and survival. In SMA, mutations in SMN1 result in a deficiency of the SMN protein, leading to motor neuron degeneration (Wirth, 2000) [Figure 7]. The SMN protein is involved in the assembly of small ribonucleoprotein particles (snRNPs), which are essential components of the spliceosome. The spliceosome is responsible for removing introns (non-coding regions) from messenger RNA (mRNA) molecules and joining the exons (coding regions) together to create mature mRNA. This process is called pre-mRNA splicing and it is critical for the proper expression of genes. Within motor neurons, the SMN protein is believed to play a role in the transport of materials within nerve cells and in maintaining the health and integrity of motor neuron axons. In individuals with SMA, there is a deficiency or absence of functional SMN protein due to mutations in the SMN1 gene. Without sufficient levels of SMN protein, motor neurons become vulnerable to degeneration and eventually die, causing the disease.

Figure 7: SMN1 and SMN2 contribute to spinal muscular atrophy (SMA) (Bowerman, 2017).

Interestingly, there is another nearly identical gene to SMN1, called SMN2. It is located near SMN1 on the genome, on chromosome 5. SMN2 also encodes the SMN protein, but it crucially differs from SMN1—it produces a majority of transcripts with exon 7 spliced out. Exon 7 skipping results in a less stable and less functional SMN protein. The severity and onset of SMA are influenced by the number of functional copies of SMN2 an individual possesses. People with more copies of SMN2 tend to have milder forms of the disease because they produce slightly more functional SMN protein (Bowerman et al., 2017) [Figure 7]. However, even individuals with several copies of SMN2 can still develop SMA, albeit with a later onset and slower progression. Recent breakthroughs in SMA research have led to the development of therapies aimed at increasing the production of functional SMN protein. These treatments include onasemnogene abeparvovec (Zolgensma), a gene therapy that delivers a functional copy of the SMN1 gene, and nusinersen (Spinraza), an antisense oligonucleotide that promotes exon 7 inclusion in SMN2 transcripts, resulting in more functional SMN protein (Reilly et al., 2023).

Charcot-Marie-Tooth Disease (CMT)

Charcot-Marie-Tooth disease (CMT), also known as hereditary motor and sensory neuropathy (HMSN), is a group of inherited neurological disorders that primarily affect the peripheral nerves, and it is the most prevalent inherited motor sensor neuropathy. These conditions lead to progressive muscle weakness, atrophy, and sensory abnormalities. CMT is named after the three physicians who first described it in the late 19th century: Jean-Martin Charcot, Pierre Marie, and Howard Henry Tooth (Pareyson & Marchesi, 2009).

The initial indicators of Charcot-Marie-Tooth (CMT) disease often manifest as walking on the toes, frequent stumbling, recurring ankle sprains, lack of coordination, and a sensation of "burning" or pins-and-needles in the hands and/or feet. As the muscles in the feet and legs waste away, individuals may experience foot drop (difficulty lifting the foot at the ankle), compromised balance, and difficulties with walking. Some may also present with hip dysplasia. Gradually, a diminished ability to perceive light touch, alterations in the sense of touch, and reduced ability to sense temperature changes may occur, and, in some cases, be lost altogether. People with CMT often struggle with tolerating cool, cold, or hot temperatures and frequently have persistently cold hands and feet. Additional symptoms can encompass bent fingers, muscle contractures, tremors, knee and/or hip issues, muscle cramps, spasms, atrophy of the thenar musclesmuscle loss between the thumb and forefinger, decreased hand strength, diminished or absent reflexes, persistent fatigue, obstructive sleep apnea, impaired circulation, scoliosis, kyphosis, and hip dysplasia [Figure 8].

Figure 8: Symptoms of Charcot-Marie-Tooth (Charcot-Marie-Tooth Association, n.d.).

CMT encompasses a diverse group of disorders with various genetic causes and clinical features. The two most common types are CMT type 1 (CMT1) and CMT type 2 (CMT2). CMT1 is characterized by demyelination of peripheral nerves, leading to slowed nerve conduction. It is primarily caused by mutations in genes related to myelin production. CMT type 2 (CMT2) is associated with axonal damage and dysfunction, which results in a different pattern of nerve conduction abnormalities (Barreto et al., 2016). Additionally, there are other, less common subtypes of CMT, such as CMT3 (also known as Dejerine-Sottas syndrome), CMT4 (various subtypes), and X-linked CMT (CMTX) (Birouk et al., 1997). CMT is a genetically heterogeneous disorder, meaning it can result from mutations in various genes. Many of these genes play critical roles in the structure and function of peripheral nerves, including those involved in myelin formation, axonal transport, and neuronal maintenance.

Mutations in the PMP22 gene are the most prevalent cause of CMT1, accounting for a significant portion of CMT cases. The PMP22 gene, located on chromosome 17, encodes a protein known as peripheral myelin protein 22 (PMP22). This protein plays a crucial role in the formation and maintenance of myelin. PMP22 is primarily found in Schwann cells, which are responsible for producing myelin in the peripheral nerves. When there are duplications or deletions in the PMP22 gene, it can disrupt the normal expression and function of the PMP22 protein. Excess PMP22 disrupts the balance of myelin formation and maintenance, causing abnormal accumulation of the protein and other cellular changes (Boutary et al., 2021). These disruptions in myelin production and maintenance can lead to demyelination. As a consequence, the nerves cannot transmit signals efficiently [Figure 9], resulting in the characteristic symptoms of CMT1.

Figure 9: PMP22 is crucial for the normal myelinization of the nerves (Charcot-Marie-Tooth & PMP22, n.d.).

Apart from PMP22, other genes that are also known to be involved in different types of CMT are MPZ, EGR2, MNF2, GDAP1, NEFL and GJB1. MPZ encodes myelin protein zero, another critical component of myelin. Mutations in this gene can result in a variety of clinical presentations (Fridman and Saporta, 2021). EGR2 is involved in regulating the expression of myelin-related genes, and mutations can disrupt myelin formation (Leonardi et al., 2019). Mutations in the MFN2 gene are a common cause of CMT2. MFN2 encodes a protein involved in mitochondrial fusion and maintenance of axonal integrity. Mutations in this gene disrupt axonal transport and mitochondrial function (Braathen et al., 2010). GDAP1 is involved in the maintenance of the peripheral nerve axon. Mutations in this gene lead to axonal degeneration (González-Sánchez et al., 2019). Mutations in the NEFL can impair axonal structure and function by affecting the neurofilaments, the structural proteins found in neurons (Kim et al., 2022). Mutations in the GJB1 gene can cause X-linked CMT, which predominantly affects males. GJB1 encodes a protein called connexin 32, which plays a role in the formation of gap junctions between Schwann cells. Mutations in this gene disrupt gap junction function, affecting myelination (Liu et al., 2017).

Friedreich's Ataxia

Friedreich's ataxia is a rare neuromuscular disorder characterized by progressive damage of the nervous system, resulting in a wide range of neurological and physical symptoms. It is named after the German physician Nikolaus Friedreich, who first described the condition in the 1860s Friedreich’s ataxia primarily affects coordination, muscle control, and balance, leading to significant disability over time (Cook & Giunti, 2017). The symptoms of Friedreich's ataxia can vary in severity and typically appear during childhood or adolescence. Common clinical features include ataxia, which is a progressive loss of coordination and balance, muscle weakness, particularly in the legs and arms, which can lead to difficulty with walking and performing daily activities, reduced or absent deep tendon reflexes, such as the knee jerk reflex, sensory abnormalities, including a desensitized sense of touch, vibration, and proprioception (awareness of body position in space), and heart abnormalities, including cardiomyopathy (enlargement of the heart) and arrhythmias, among others [Figure 10].

Figure 10: Symptoms of Friedreich’s ataxia (Cleveland Clinic, n.d.).

Friedreich's ataxia is caused by mutations in the FXN gene, located on chromosome 9. These mutations typically involve the expansion of a specific DNA sequence called GAA repeats within the gene. FXN gene encodes the frataxin protein, which is critical for mitochondrial function, particularly in the process of iron-sulfur cluster (Fe-S cluster) biogenesis. Fe-S clusters are essential cofactors of various mitochondrial enzymes responsible for energy production and other cellular processes. Frataxin, apart from helping assemble these clusters, regulates iron levels within the mitochondria. The GAA repeat expansion in the FXN gene leads to reduced production of the frataxin protein (Williams & De Jesus, 2023). This deficiency disrupts the normal processes within the mitochondria, leading to increased oxidative stress, mitochondrial dysfunction, and damage to nerve cells and other tissues [Figure 11].

The precise mechanism through which the GAA repeat expansion leads to a decrease in frataxin expression is not fully understood. However, two hypotheses have been proposed to explain this phenomenon. Firstly, based on evidence from in vitro and cell transfection studies, it is suggested that the GAA repeat expansion may form abnormal non-B DNA structures, such as triplexes or "sticky DNA," or DNA-RNA hybrid structures known as R-loops. These structures could potentially obstruct the process of RNA polymerase II, thereby reducing the expression of the FXN gene (Groh et al., 2014). Secondly, there is supporting evidence indicating that GAA repeat expansions may trigger gene-silencing effects mediated by heterochromatin (Kim et al., 2011). In line with this hypothesis, several epigenetic changes associated with Friederich's ataxia disease have been identified in the immediate vicinity of the expanded GAA repeats within the FXN gene.

Figure 11: Overview of Friedreich’s ataxia deregulations following frataxin deficiency (La Rosa, 2020).

Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a progressive neurodegenerative disorder that primarily affects motor neurons in the brain and spinal cord. It leads to the gradual loss of motor function, muscle weakness, and, ultimately, paralysis. ALS is relentlessly progressive, with most individuals experiencing a gradual decline in motor function over time. The rate of progression can vary widely among individuals, with some experiencing a more rapid decline than others. While most cases of ALS occur sporadically without a known family history, about 5-10% of cases are inherited (familial ALS), with specific genetic mutations identified in genes such as SOD1, C9orf72, FUS, and others. The vast majority of ALS cases, however, are sporadic, and the exact cause remains unclear. Environmental factors, including exposure to toxins or traumatic brain injuries, have been investigated as potential contributors to sporadic ALS.

Mutations in the SOD1 gene were among the first genetic abnormalities linked to familial ALS. The SOD1 gene encodes an enzyme that plays a crucial role in antioxidant defence within cells. It is part of a group of enzymes known as superoxide dismutases, which are responsible for breaking down superoxide radicals, a type of reactive oxygen species (ROS) that are generated during normal cellular metabolism and can be toxic. Mutations in the SOD1 gene lead to the production of abnormal forms of the SOD1 enzyme (Tafuri et al., 2015). These mutant forms of SOD1 are believed to acquire toxic properties, potentially disrupting cellular processes, and causing damage to motor neurons [Figure 12]. The exact mechanisms by which mutant SOD1 leads to motor neuron degeneration in ALS are still under investigation, but it is thought to involve a combination of toxic gain-of-function properties and loss of normal SOD1 function.

Figure 12: Mechanisms for SOD1-related ALS (Peggion, 2022).

The expansion of a hexanucleotide repeat (GGGGCC) in the C9orf72 gene is the most common genetic cause of ALS and also a common cause of frontotemporal dementia (FTD), another neurodegenerative disorder. The exact mechanisms by which this repeat expansion leads to disease are complex and not fully understood. The normal function of the C9orf72 gene is not fully understood, but it is believed to play a role in cellular processes related to membrane trafficking and autophagy, which are essential for cellular waste clearance and maintenance of cellular health (Balendra and Isaacs, 2018). Mutations in the FUS gene can also cause familial ALS. FUS is an RNA-binding protein involved in various cellular processes, including RNA metabolism. Mutations in FUS are believed to disrupt RNA processing and lead to motor neuron dysfunction. However, the exact mechanism is still unknown (Zhou et al., 2022).


Neuromuscular genetic diseases encompass a wide range of disorders that deeply affect the nervous system, muscles, or both cell types. These conditions, often rooted in inherited genetic mutations, bring about a diverse array of symptoms, posing significant challenges for individuals and their families. From the debilitating muscle weakness seen in muscular dystrophies like Duchenne and myotonic dystrophy to the coordination difficulties of Charcot-Marie-Tooth disease, each neuromuscular genetic disorder comes with its unique set of clinical features and genetic causes. Understanding the genetic basis of these diseases has set the stage for groundbreaking research and innovative therapies aiming to alleviate symptoms and slow down disease progression.

In the realm of neuromuscular genetic diseases, genetic research and innovative therapies shine as beacons of hope. As scientists and medical professionals strive to unravel the genetic mysteries of these conditions, there is a growing sense of optimism that better treatments and even potential cures, might not be far off. Indeed, as summarized in the article, there are some diseases that can be already treated with gene therapy with promising results. These advancements offer comfort to patients and their families, holding the promise of a brighter future where the weight of neuromuscular genetic diseases could be lightened, allowing the pursuit of health and well-being to continue. The prospect of a future where these conditions can be effectively managed or cured highlights the vital role of ongoing research and collaborative efforts within the scientific and medical communities.

Bibliographical References

Abati, E., Bresolin, N., Comi, G., & Corti, S. (2020). Silence superoxide dismutase 1 (SOD1): A promising therapeutic target for amyotrophic lateral sclerosis (ALS). Expert Opinion on Therapeutic Targets, 24(4), 295–310.

Aldrich, J.E. (2007). Basic physics of ultrasound imaging. Critical Care Medicine, 35(5 Suppl), S131-7.

Audic, F., & Barnerias, C. (2020). Spinal muscular atrophy (SMA) type I (Werdnig-Hoffmann disease). Archives de Pediatrie, 27(7S), 7S15-7S17.

Balendra, R., & Isaacs, A.M. (2018). C9orf72-mediated ALS and FTD: Multiple pathways to disease. Nature Reviews. Neurology, 14(9), 544–558.

Barreto, L.C.L.S., Oliveira, F.S., Nunes, P.S., de França Costa, I.M.P., Garcez, C.A., Goes, G.M., Neves, E.L.A., de Souza Siqueira Quintans, J., & de Souza Araújo, A.A. (2016). Epidemiologic study of Charcot-Marie-Tooth disease: A systematic review. Neuroepidemiology, 46(3), 157–165.

Birouk, N., Maisonobe, T., Le Forestier, N., Gouider, R., Léger, J.M., & Bouche, P. (1997). Charcot-Marie-Tooth disease: Electromyography is still useful in diagnosis and classification. Revue Neurologique (Paris), 153(12), 727–736.

Boutary, S., Echaniz-Laguna, A., Adams, D., Loisel-Duwattez, J., Schumacher, M., Massaad, C., & Massaad-Massade, L. (2021). Treating PMP22 gene duplication-related Charcot-Marie-Tooth disease: the past, the present and the future. Translational Research, 227, 100–111.

Bowerman, M., Becker, C., Yáñez-Muñoz, R., Ning, K., Wood, M., Gillingwater, T., & Talbot, K. (2017). Therapeutic strategies for spinal muscular atrophy: SMN and beyond. Disease Models & Mechanisms, 10(8), 943–954.

Braathen, G.J., S, J.C., Lobato, A., Høyer, H., & Russell, M.B. (2010). MFN2 point mutations occur in 3.4% of Charcot-Marie-Tooth families. An investigation of 232 Norwegian CMT families. BMC Medical Genetics, 11, 48.

Cook, A., & Giunti, P. (2017). Friedreich’s ataxia: Clinical features, pathogenesis and management. British Medical Bulletin, 124(1), 19–30.

D’Amico, A., Mercuri, E., Tiziano, F.D., & Bertini, E. (2011). Spinal muscular atrophy. Orphanet Journal of Rare Diseases, 6, 71.

Van Daele, S.H., Moisse, M., van Vugt, J.J.F.A., Zwamborn, R.A.J., van der Spek, R., van Rheenen, W., Van Eijk, K., Kenna, K., Corcia, P., Vourc’h, P., et al. (2023). Genetic variability in sporadic amyotrophic lateral sclerosis. Brain, 146(9), 3760–3769.

Duan, D., Goemans, N., Takeda, S., Mercuri, E., & Aartsma-Rus, A. (2021). Duchenne muscular dystrophy. Nature Reviews. Disease Primers, 7(1), 13.

Eng, C., Skolnick, A.E., & Come, S.E. (1990). Elevated creatine kinase and malignancy. Hospital Practice (Office Ed)., 25(12), 123,126,129-130.

Feldman, E.L., Goutman, S.A., Petri, S., Mazzini, L., Savelieff, M.G., Shaw, P.J., & Sobue, G. (2022). Amyotrophic lateral sclerosis. Lancet (London, England), 400(10360), 1363–1380.

Flanigan, K.M. (2014). Duchenne and Becker muscular dystrophies. Neurologic Clinics 32(3), 671–688, viii.

Fortunato, F., Farnè, M., and Ferlini, A. (2021). The DMD gene and therapeutic approaches to restore dystrophin. Neuromuscular Disorders, 31(10), 1013–1020.

Fridman, V., & Saporta, M.A. (2021). Mechanisms and treatments in demyelinating CMT. Neurotherapeutics, 18(4), 2236–2268.

Glover, G.H. (2011). Overview of functional magnetic resonance imaging. Neurosurgery Clinics of North America, 22(2), 133–139, vii.

González-Sánchez, P., Satrústegui, J., Palau, F., & Del Arco, A. (2019). Calcium deregulation and mitochondrial bioenergetics in GDAP1-related CMT disease. International Journal of Molecular Sciences, 20(2), 403.

Groh, M., Lufino, M.M.P., Wade-Martins, R., & Gromak, N. (2014). R-loops associated with triplet repeat expansions promote gene silencing in Friedreich ataxia and fragile X syndrome. PLoS Genetics, 10(5), e1004318.

Janas, J. (1996). Muscular dystrophy. Nurse Practitioner Forum, 7(4), 167–173.

Kaliman, P., & Llagostera, E. (2008). Myotonic dystrophy protein kinase (DMPK) and its role in the pathogenesis of myotonic dystrophy 1. Cellular Signalling, 20(11), 1935–1941.

Kim, E., Napierala, M., & Dent, S.Y.R. (2011). Hyperexpansion of GAA repeats affects post-initiation steps of FXN transcription in Friedreich’s ataxia. Nucleic Acids Research, 39(19), 8366–8377.

Kim, H.J., Kim, S.B., Kim, H.S., Kwon, H.M., Park, J.H., Lee, A.J., Lim, S.O., Nam, S.H., Hong, Y. Bin, Chung, K.W., et al. (2022). Phenotypic heterogeneity in patients with NEFL-related Charcot-Marie-Tooth disease. Molecular Genetics & Genomic Medicine, 10(2), e1870.

Kolb, S.J., & Kissel, J.T. (2015). Spinal muscular atrophy. Neurologic Clinics, 33(4), 831–846.

Leonardi, L., Garibaldi, M., Fionda, L., Vanoli, F., Loreti, S., Morino, S., & Antonini, G. (2019). Widening the phenotypical spectrum of EGR2-related CMT: Unusual phenotype for R409W mutation. Clinical Neurophysiology, 130(1), 93–94.

Liu, L., Li, X.B., Hu, Z.H.M., Zi, X.H., Zhao, X., Xie, Y.Z., Huang, S.H.X., Xia, K., Tang, B.S., & Zhang, R.X. (2017). Phenotypes and cellular effects of GJB1 mutations causing CMT1X in a cohort of 226 Chinese CMT families. Clinical Genetics, 91(6), 881–891.

Massey, T., McAllister, B., & Jones, L. (2018). Methods for assessing DNA repair and repeat expansion in Huntington’s disease. Methods in Molecular Biology, 1780, 483–495.

Meola, G. (2020). Myotonic dystrophy type 2: The 2020 update. Acta Myologica, 39(4), 222–234.

Mocciaro, E., Runfola, V., Ghezzi, P., Pannese, M., & Gabellini, D. (2021). DUX4 role in normal physiology and in FSHD muscular dystrophy. Cells, 10(12), 3322.

Nix, J.S., & Moore, S.A. (2020). What every neuropathologist needs to know: The muscle biopsy. Journal of Neuropathology and Experimental Neurology, 79(7), 719–733.

Pandey, S.N., Kesari, A., Yokota, T., & Pandey, G.S. (2015). Muscular dystrophy: Disease mechanisms and therapies. BioMed Research International 2015, 456348.

Pareyson, D., & Marchesi, C. (2009). Diagnosis, natural history, and management of Charcot-Marie-Tooth disease. The Lancet Neurology, 8(7), 654–667.

Reilly, A., Chehade, L., & Kothary, R. (2023). Curing SMA: Are we there yet? Gene Therapy, 30(1-2), 8–17.

Rubin, D.I. (2019). Needle electromyography: Basic concepts. Handbook of Clinical Neurology 160, 243–256.

Salort-Campana, E., & Quijano-Roy, S. (2020). Clinical features of spinal muscular atrophy (SMA) type 3 (Kugelberg-Welander disease). Archives de Pediatrie, 27(7S), 7S23-7S28.

Tafuri, F., Ronchi, D., Magri, F., Comi, G.P., & Corti, S. (2015). SOD1 misplacing and mitochondrial dysfunction in amyotrophic lateral sclerosis pathogenesis. Frontiers in Cellular Neuroscience, 9, 336.

Tavee, J. (2019). Nerve conduction studies: Basic concepts. Handbook of Clinical Neurology, 160, 217–224.

Turner, C., & Hilton-Jones, D. (2014). Myotonic dystrophy: diagnosis, management and new therapies. Current Opinion in Neurology, 27(5), 599–606.

Wadman, R.I., van der Pol, W.L., Bosboom, W.M., Asselman, F.-L., van den Berg, L.H., Iannaccone, S.T., & Vrancken, A.F. (2020). Drug treatment for spinal muscular atrophy types II and III. The Cochrane Database of Systematic Reviews, 1(1), CD006282.

Williams, C.T., & De Jesus, O. (2023). Friedreich Ataxia. In StatPearls. StatPearls Publishing.

Wirth, B. (2000). An update of the mutation spectrum of the survival motor neuron gene (SMN1) in autosomal recessive spinal muscular atrophy (SMA). Human Mutation, 15(3), 228–237.;2-9

Zhou, B., Zheng, Y., Li, X., Dong, H., Yu, J., Zou, Y., Zhu, M., Yu, Y., Fang, X., Zhou, M., Zhang, W., Yuan, Y., Wang, Z., Deng, J., & Hong, D. (2022). FUS mutation causes disordered lipid metabolism in skeletal muscle associated with ALS. Molecular Neurobiology, 59(12), 7265–7277.

Visual Sources

Cover Image. A nerve connected to a muscle. [Image] Drug Target Review. Retrieved on 05th October, 2023 from

Figure 1: [Electromyography (EMG) evaluates the health and function of skeletal muscles and the nerves that control them.] [Image] Cleveland Clinic. Retrieved on 05th October, 2023 from Figure 2: [Muscular dystrophy is a complex and diverse group of genetic disorders characterized by progressive muscle weakening that worsen over time.] [Image] Research Outreach. Retrieved on 05th October, 2023 from Figure 3: [Dystrophin is crucial in facilitating the transmission of muscle contraction force from within the muscle cell to the cell membrane.] [Image] Muscular Dystrophy Association. Retrieved on 05th October, 2023 from Figure 4: (Mocciaro, 2021) [Physiological and pathological roles of DUX4.] [Image] Cells. Retrieved on 05th October, 2023 from Figure 5: [Symptoms of the myotonic dystrophy.] [Image] Very Well Health. Retrieved on 05th October, 2023 from Figure 6: [The degeneration of motor neurons leads to atrophy.] [Image] Together in SMA. Retrieved on 05th October, 2023 from Figure 7: (Bowerman, 2017) [SMN1 and SMN2 contribute to spinal muscular atrophy (SMA)]. [Image]. Disease Models and Mechanisms. Retrieved on 05th October, 2023 from Figure 8: [Symptoms of Charcot-Marie-Tooth.] [Image] Charcot-Marie-Tooth Association. Retrieved on 05th October, 2023 from Figure 9: [PMP22 is crucial for the normal myelization of the nerves.] [Image] Charcot-Marie-Tooth & PMP22. Retrieved on 05th October, 2023 from Figure 10: [Symptoms of Friedreich’s ataxia.] [Image] Cleveland Clinic. Retrieved on 05th October, 2023 from Figure 11: (La Rosa, 2020) [Overview of Friedreich’s ataxia deregulations following frataxin deficiency.] [Image] International Journal of Molecular Science. Retrieved on 05th October, 2023 from Figure 12: (Peggion, 2022) [Mechanisms for SOD1-related ALS.] [Image] Antioxidants. Retrieved on 05th October, 2023 from


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Ainoa Planas Riverola

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