Materiały źródłowe

• #1 Spinal Muscle Atrophy – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560687/

  Spinal muscular atrophy (SMA) denotes a collection of inherited clinical syndromes causing degeneration of anterior horn cells in the spinal cord with associated destruction of alpha motor cells and presents clinically with characteristic proximal muscle weakness and atrophy. Homozygous deletion at 5q13 (the coding region for the survival motor neuron (SMN1) gene) is responsible for 95% of cases of SMA, and after cystic fibrosis is the second most common cause of autosomal recessive inherited related mortality with an estimated incidence of 1 in 6000 to 11000. […] In 95% of cases, SMA results from a homozygous deletion of SMN1 on chromosome 5q13; however, this does not explain how there can be significant clinical heterogeneity in phenotype. The answer lies in there being two versions of SMN: 1) telemoeric version (SMN1) 2) centromeric version (SMN2) with individuals varying in the number of copies of SMN2 they possess.

• #2 Spinal muscular atrophy – UpToDate

  https://www.uptodate.com/contents/spinal-muscular-atrophy

  Spinal muscular atrophy (SMA) is characterized by degeneration of the anterior horn cells in the spinal cord and motor nuclei in the lower brainstem, which results in progressive muscle weakness and atrophy. […] The inheritance pattern of chromosome 5q-related SMA is autosomal recessive. The different forms of 5q-SMA are caused by biallelic deletions or mutations in the SMN1 gene on chromosome 5q13.2, resulting in a deficiency of the SMN1 protein. […] While the most common forms of SMA are caused by deletions or mutations in the SMN1 on chromosome 5q (ie, 5q SMAs), there are many rare non-5q spinal muscular atrophies. […] The incidence of spinal muscular atrophy ranges from 5 to 13 per 100,000 live births, and the carrier frequency of disease-causing SMN1 mutations ranges from 1:100 to 1:45, with marked interethnic variability. SMA is the most common monogenic cause of infant mortality.

• #3 Spinal Muscular Atrophy | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/spinal-muscular-atrophy

  Spinal muscular atrophy (SMA) refers to a group of hereditary diseases which affect motor neurons. The most common form of SMA is caused by changes in a gene known as the survival motor neuron gene 1 (SMN1). There is a gene very similar to SMN1 called SMN2, which may be present in multiple copies. Although the SMN2 gene makes much less of the SMN protein than the healthy SMN1 gene, extra copies of the SMN2 gene are associated with the less severe forms of SMA (Types II-IV). […] People living with SMA have insufficient levels of the survival motor neuron (SMN) protein, which maintains the health and normal function of motor neurons. Insufficient levels of SMN protein leads to loss of motor neurons in the spinal cord and causes weakness and wasting of the skeletal muscles. The most common form of SMA is caused by the SMN1 gene; however, there are other forms of SMA associated with other genes. […] Less common SMA forms are caused by changes in other genes, including the: IGHMBP2 gene on chromosome 11, MORC2 gene on chromosome 22, UBA1 gene on the X chromosome, DYNC1H1 gene on chromosome 14, BICD2 gene on chromosome 9, TRPV4 on chromosome 12.

• #4 SMA (Spinal Muscular Atrophy): What It Is, Symptoms & Types

  https://my.clevelandclinic.org/health/diseases/14505-spinal-muscular-atrophy-sma

  Spinal muscular atrophy (SMA) is a genetic condition that causes worsening muscle weakness. […] SMA involves the loss of a specific type of nerve cell in your spinal cord called lower motor neurons, or anterior horn cells. These cells control muscle movement. Without these motor neurons, muscles dont receive the nerve signals that make them move. […] SMA is a genetic condition, which means you inherit genes from your biological parents that cause the condition. […] Mutations (changes) in the SMN1 (survivor motor neuron 1) gene cause all types of spinal muscular atrophy. The number of copies that you have of the SMN2 gene alters the severity of the condition. […] A healthy SMN1 gene produces SMN protein. Motor neurons need this protein to survive and function properly. If you have SMA, your body doesnt make enough SMN protein, so your motor neurons shrink and die.

• #5 Spinal Muscle Atrophy: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1264401-overview

  Patients with SMA have a homozygous deletion of the telomeric SMN gene SMN1, which is found in arm 5q13 (bands q11.2-13.3). This deletion has been demonstrated in as many as 98% of patients with SMA. […] SMN1 encodes the SMN protein, which is part of a multiprotein complex required for the biogenesis of small nuclear ribonucleoproteins. […] The SMN protein is critical to the health and survival of the nerve cells in the spinal cord that are responsible for muscle contraction (motor neurons). […] A second gene also plays a role in producing the SMN protein namely, SMN2, often called the SMA „backup gene.” […] The severity of SMA is inversely related to the number of copies of SMN2. […] The SMN2 gene copy number is related to, but not predictive of, disease severity, and care decisions should not be made on the basis of copy number alone. […] A significant increase in nuclear DNA vulnerability was detected in fetuses with SMA at 12-15 weeks’ gestational age.

• #6 Causes/Inheritance – Spinal Muscular Atrophy (SMA) – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/spinal-muscular-atrophy/causes-inheritance

  SMA is characterized by the loss of motor neurons, nerve cells in the spinal cord. It is classified as a motor neuron disease. […] The most common form of SMA (types 1-4) is caused by a defect (mutation) in the SMN1 gene on chromosome 5. […] In 94% of all SMA cases, this mutation involves a deletion in a segment known as exon 7. […] A mutation in the SMN1 gene leads to a deficiency of a motor neuron protein called SMN, which stands for survival of motor neuron. […] More rarely, a mutation in an X-chromosome gene called UBE1 causes X-linked SMA. […] Flaws in the cytoplasmic dynein 1 heavy chain 1 (DYNC1H1) gene on chromosome 14 have been found to lead to another rare form of SMA called SMA-LED. […] Normally, SMN1 genes produce full-length and fully functional SMN protein. […] But when the SMN1 gene has mutations, as in the chromosome 5-related form of SMA, insufficient levels of SMN protein are produced.

• #7 Spinal Muscle Atrophy – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560687/

  Spinal muscular atrophy (SMA) denotes a collection of inherited clinical syndromes causing degeneration of anterior horn cells in the spinal cord with associated destruction of alpha motor cells and presents clinically with characteristic proximal muscle weakness and atrophy. Homozygous deletion at 5q13 (the coding region for the survival motor neuron (SMN1) gene) is responsible for 95% of cases of SMA, and after cystic fibrosis is the second most common cause of autosomal recessive inherited related mortality with an estimated incidence of 1 in 6000 to 11000. […] In 95% of cases, SMA results from a homozygous deletion of SMN1 on chromosome 5q13; however, this does not explain how there can be significant clinical heterogeneity in phenotype. The answer lies in there being two versions of SMN: 1) telemoeric version (SMN1) 2) centromeric version (SMN2) with individuals varying in the number of copies of SMN2 they possess.

• #8 Spinal Muscular Atrophy (SMA) | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/spinal-muscular-atrophy-sma

  Spinal muscular atrophy (SMA) is a genetic disease that affects the spinal cord and nerves, resulting in muscle wasting and weakness. Untreated, it is a neurodegenerative, progressive disease, which can be fatal in its more severe forms. […] In most cases, SMA is an autosomal recessive disease. This means that both males and females are equally affected, and that two mutated copies of the gene, one inherited from each parent, are necessary to have the condition. […] SMA is caused by mutations in a gene called survival motor neuron 1 (or SMN1). In more than 95% of cases of SMA, the mutation is a common deletion; less commonly, there are spelling errors, also called point mutations, in SMN1 or other genetic variants. […] When both parents are carriers (or they each have one abnormal copy of the gene and one normal copy), there is a one in four (25%) chance, with each pregnancy, to have a child with SMA.

• #9 What causes SMA?

  https://care.togetherinsma-qa.com/en/home/what-is-sma/what-causes-sma.html

  SMA is a rare genetic neuromuscular disease caused by a mutation in the survival motor neuron 1 (SMN1) gene. This gene is responsible for producing survival motor neuron (SMN) protein, which maintains the health and normal function of motor neurons. The degeneration of motor neurons leads to a gradual decrease in the mass and strength of muscles (atrophy). […] Unlike many other rare neuromuscular diseases, there is a clear understanding of the specific genetic cause of spinal muscular atrophy. SMA is caused by a mutation in the survival motor neuron 1 (SMN1) gene, which is responsible for producing survival motor neuron (SMN) protein. This protein maintains the health and normal function of motor neurons. […] In people with spinal muscular atrophy, both copies of the SMN1 gene are mutated, leading to a decreased production of SMN protein. Without a proper level of SMN protein, motor neurons in the spinal cord will be lost, preventing the muscles from receiving proper signals from the brain.

• #10 Spinal Muscle Atrophy: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1264401-overview

  Patients with SMA have a homozygous deletion of the telomeric SMN gene SMN1, which is found in arm 5q13 (bands q11.2-13.3). This deletion has been demonstrated in as many as 98% of patients with SMA. […] SMN1 encodes the SMN protein, which is part of a multiprotein complex required for the biogenesis of small nuclear ribonucleoproteins. […] The SMN protein is critical to the health and survival of the nerve cells in the spinal cord that are responsible for muscle contraction (motor neurons). […] A second gene also plays a role in producing the SMN protein namely, SMN2, often called the SMA „backup gene.” […] The severity of SMA is inversely related to the number of copies of SMN2. […] The SMN2 gene copy number is related to, but not predictive of, disease severity, and care decisions should not be made on the basis of copy number alone. […] A significant increase in nuclear DNA vulnerability was detected in fetuses with SMA at 12-15 weeks’ gestational age.

• #11 SMA (Spinal Muscular Atrophy): What It Is, Symptoms & Types

  https://my.clevelandclinic.org/health/diseases/14505-spinal-muscular-atrophy-sma

  Spinal muscular atrophy (SMA) is a genetic condition that causes worsening muscle weakness. […] SMA involves the loss of a specific type of nerve cell in your spinal cord called lower motor neurons, or anterior horn cells. These cells control muscle movement. Without these motor neurons, muscles dont receive the nerve signals that make them move. […] SMA is a genetic condition, which means you inherit genes from your biological parents that cause the condition. […] Mutations (changes) in the SMN1 (survivor motor neuron 1) gene cause all types of spinal muscular atrophy. The number of copies that you have of the SMN2 gene alters the severity of the condition. […] A healthy SMN1 gene produces SMN protein. Motor neurons need this protein to survive and function properly. If you have SMA, your body doesnt make enough SMN protein, so your motor neurons shrink and die.

• #12 Causes/Inheritance – Spinal Muscular Atrophy (SMA) – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/spinal-muscular-atrophy/causes-inheritance

  A neighboring gene on chromosome 5, called SMN2, also produces SMN protein. […] People can have multiple copies of the SMN2 gene. […] In the chromosome 5-related form of SMA, the more SMN2 gene copies a person has, the more functional SMN protein is available. […] SMA severity also may depend on disease modifiers, which don’t cause disease but can affect (modify) onset and severity by influencing various biological pathways. […] Chromosome 5-related SMA (types 1 through 4) follows an inheritance pattern known as autosomal recessive. […] If both parents are carriers of the chromosome 5 gene flaw, the risk of each pregnancy producing a child with the disease is 25%. […] X-linked SMA is inherited via the X chromosome. […] Additionally, SMA can be caused by mutations in the DYNC1H1 gene on chromosome 14. This form is dominantly inherited, meaning that only one DYNC1H1 gene mutation, inherited from one parent, is sufficient to cause the disease.

• #13 Spinal muscular atrophy – TREAT-NMD

  https://www.treat-nmd.org/resources-and-support/neuromuscular-disease-information/spinal-muscular-atrophy/

  In unaffected people, the SMN1 gene produces full length and fully functional SMN protein, but when it has mutations, insufficient levels of SMN protein are produced. […] However, a neighbouring gene on chromosome 5, SMN2, also produces SMN protein and a small percentage of the protein is functional. […] The more copies of the SMN2 gene a person with SMA has, the milder the disease course is likely to be.

• #14 Spinal Muscular Atrophy (SMA) | Children’s Hospital of Philadelphia

  https://www.chop.edu/conditions-diseases/spinal-muscular-atrophy-sma

  SMA is caused not by an absence of SMN protein, like many other disorders, but by a deficiency. Everyone still makes some SMN protein, from a gene called SMN2. However, each SMN2 gene functions about 10-15% as well as a SMN1 gene. The copy number of SMN2 genes correlates with disease severity, and is responsible for some of the broad variety in clinical presentation.

• #15 Spinal muscular atrophy: MedlinePlus GeneticsLock

  https://medlineplus.gov/genetics/condition/spinal-muscular-atrophy/

  Spinal muscular atrophy is a genetic disorder characterized by weakness and wasting (atrophy) in muscles used for movement (skeletal muscles). It is caused by a loss of specialized nerve cells, called motor neurons that control muscle movement. […] Mutations in the SMN1 gene cause all types of spinal muscular atrophy described above. The number of copies of the SMN2 gene modifies the severity of the condition and helps determine which type develops. […] Most people with spinal muscular atrophy are missing a piece of the SMN1 gene, which impairs SMN protein production. A shortage of SMN protein leads to motor neuron death, and as a result, signals are not transmitted between the brain and muscles. […] Typically, people have two copies of the SMN1 gene and one to two copies of the SMN2 gene in each cell. However, the number of copies of the SMN2 gene varies, with some people having up to eight copies. […] Spinal muscular atrophy is inherited in an autosomal recessive pattern, which means both copies of the SMN1 gene in each cell have mutations.

• #16 Causes/Inheritance – Spinal Muscular Atrophy (SMA) – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/spinal-muscular-atrophy/causes-inheritance

  A neighboring gene on chromosome 5, called SMN2, also produces SMN protein. […] People can have multiple copies of the SMN2 gene. […] In the chromosome 5-related form of SMA, the more SMN2 gene copies a person has, the more functional SMN protein is available. […] SMA severity also may depend on disease modifiers, which don’t cause disease but can affect (modify) onset and severity by influencing various biological pathways. […] Chromosome 5-related SMA (types 1 through 4) follows an inheritance pattern known as autosomal recessive. […] If both parents are carriers of the chromosome 5 gene flaw, the risk of each pregnancy producing a child with the disease is 25%. […] X-linked SMA is inherited via the X chromosome. […] Additionally, SMA can be caused by mutations in the DYNC1H1 gene on chromosome 14. This form is dominantly inherited, meaning that only one DYNC1H1 gene mutation, inherited from one parent, is sufficient to cause the disease.

• #17 Spinal Muscle Atrophy – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560687/

  Patients with SMA are lacking SMN1 and are therefore dependent on residual SMN2 production of functional SMN protein for alpha motor neuron function and subsequent survival. There is, therefore, a positive correlation seen between the number of copies of SMN2 and phenotype severity with SMA type 1 typically having 1 to 2 copies of SMN2 and SMA type 4 having 3 to 5 SMN2 copies. […] There is not a perfect correlation as there are anomalies in phenotypic variation in SMN2, leading to varying amounts of functional SMN protein production in different individuals. Therefore a low number of SMN2 copies with a milder clinical phenotype have been described.

• #18 Spinal Muscular Atrophy Pathophysiology | mySMAteam

  https://www.mysmateam.com/resources/spinal-muscular-atrophy-pathophysiology

  SMA is inherited in an autosomal recessive manner, which means that someone who inherits the disease has two copies of the mutated SMN1 gene one from each parent. Sometimes, however, the gene isnt mutated, but completely missing. This is called a deletion. […] But SMN1 isnt working alone to cause SMA. The amount of full-length (or functional) SMN protein someone makes also depends on the interaction between SMN1 and another gene SMN2. The SMN2 gene is near SMN1 on the chromosome (a molecule of genetic material), and they work together to make functional SMN protein. People can have between zero and eight copies of the SMN2 gene. The number of SMN2 copies and the amount of functional SMN protein produced correlates with how severe the disease is. The more copies of the SMN2 gene a child has, the better their prognosis (disease outlook or chance of survival) will be. Fewer copies of the SMN2 gene leads to a more serious disease course. In fact, the number of copies of SMN2 someone has plays a role in the type of SMA they develop.

• #19 Spinal Muscle Atrophy – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560687/

  Patients with SMA are lacking SMN1 and are therefore dependent on residual SMN2 production of functional SMN protein for alpha motor neuron function and subsequent survival. There is, therefore, a positive correlation seen between the number of copies of SMN2 and phenotype severity with SMA type 1 typically having 1 to 2 copies of SMN2 and SMA type 4 having 3 to 5 SMN2 copies. […] There is not a perfect correlation as there are anomalies in phenotypic variation in SMN2, leading to varying amounts of functional SMN protein production in different individuals. Therefore a low number of SMN2 copies with a milder clinical phenotype have been described.

• #20 Spinal Muscle Atrophy – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK560687/

  Patients with SMA are lacking SMN1 and are therefore dependent on residual SMN2 production of functional SMN protein for alpha motor neuron function and subsequent survival. There is, therefore, a positive correlation seen between the number of copies of SMN2 and phenotype severity with SMA type 1 typically having 1 to 2 copies of SMN2 and SMA type 4 having 3 to 5 SMN2 copies. […] There is not a perfect correlation as there are anomalies in phenotypic variation in SMN2, leading to varying amounts of functional SMN protein production in different individuals. Therefore a low number of SMN2 copies with a milder clinical phenotype have been described.

• #21 Spinal Muscle Atrophy: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1264401-overview

  Patients with SMA have a homozygous deletion of the telomeric SMN gene SMN1, which is found in arm 5q13 (bands q11.2-13.3). This deletion has been demonstrated in as many as 98% of patients with SMA. […] SMN1 encodes the SMN protein, which is part of a multiprotein complex required for the biogenesis of small nuclear ribonucleoproteins. […] The SMN protein is critical to the health and survival of the nerve cells in the spinal cord that are responsible for muscle contraction (motor neurons). […] A second gene also plays a role in producing the SMN protein namely, SMN2, often called the SMA „backup gene.” […] The severity of SMA is inversely related to the number of copies of SMN2. […] The SMN2 gene copy number is related to, but not predictive of, disease severity, and care decisions should not be made on the basis of copy number alone. […] A significant increase in nuclear DNA vulnerability was detected in fetuses with SMA at 12-15 weeks’ gestational age.

• #22 Causes/Inheritance – Spinal Muscular Atrophy (SMA) – Diseases | Muscular Dystrophy Association

  https://www.mda.org/disease/spinal-muscular-atrophy/causes-inheritance

  A neighboring gene on chromosome 5, called SMN2, also produces SMN protein. […] People can have multiple copies of the SMN2 gene. […] In the chromosome 5-related form of SMA, the more SMN2 gene copies a person has, the more functional SMN protein is available. […] SMA severity also may depend on disease modifiers, which don’t cause disease but can affect (modify) onset and severity by influencing various biological pathways. […] Chromosome 5-related SMA (types 1 through 4) follows an inheritance pattern known as autosomal recessive. […] If both parents are carriers of the chromosome 5 gene flaw, the risk of each pregnancy producing a child with the disease is 25%. […] X-linked SMA is inherited via the X chromosome. […] Additionally, SMA can be caused by mutations in the DYNC1H1 gene on chromosome 14. This form is dominantly inherited, meaning that only one DYNC1H1 gene mutation, inherited from one parent, is sufficient to cause the disease.

• #23 Spinal muscular atrophy (SMA) – NHS

  https://www.nhs.uk/conditions/spinal-muscular-atrophy-sma/

  Most types of spinal muscular atrophy (SMA) are caused by an altered gene called SMN1 being passed on to a child by their parents (inherited). […] The parents do not usually have SMA themselves, which is known as „carrying” the gene. In most cases, SMA can only be passed on if both parents carry the altered gene. […] If both parents carry the altered gene, there’s a: 1 in 4 (25%) chance their child will have SMA, 2 in 4 (50%) chance their child will carry the altered gene, but will not have SMA, 1 in 4 (25%) chance their child will not carry the altered gene or have SMA. […] The chances of a child inheriting SMA can be different for some rarer types of SMA. Some rarer types are not passed on at all.

• #24 SMA (Spinal Muscular Atrophy): What It Is, Symptoms & Types

  https://my.clevelandclinic.org/health/diseases/14505-spinal-muscular-atrophy-sma

  You inherit SMA in an autosomal recessive pattern, which means both of your biological parents pass on mutations in the SMN1 gene. In most cases, the biological parents of someone with an autosomal recessive condition each carry one copy of the mutated gene. But these carriers typically dont have symptoms of the condition.

• #25 Spinal muscular atrophy (SMA) – NHS

  https://www.nhs.uk/conditions/spinal-muscular-atrophy-sma/

  Most types of spinal muscular atrophy (SMA) are caused by an altered gene called SMN1 being passed on to a child by their parents (inherited). […] The parents do not usually have SMA themselves, which is known as „carrying” the gene. In most cases, SMA can only be passed on if both parents carry the altered gene. […] If both parents carry the altered gene, there’s a: 1 in 4 (25%) chance their child will have SMA, 2 in 4 (50%) chance their child will carry the altered gene, but will not have SMA, 1 in 4 (25%) chance their child will not carry the altered gene or have SMA. […] The chances of a child inheriting SMA can be different for some rarer types of SMA. Some rarer types are not passed on at all.

• #26 Carrier Screening for Spinal Muscular Atrophy (SMA) | ACOG

  https://www.acog.org/womens-health/faqs/carrier-screening-for-spinal-muscular-atrophy

  Spinal muscular atrophy (SMA) is a genetic disorder that affects the nerves of the spine. These nerves control muscles for breathing, swallowing, and movement of the arms and legs. SMA causes these muscles to atrophy (get smaller) and become very weak. Depending on the type, SMA can cause severe disability and death. SMA does not affect mental ability. […] SMA is caused by changes (called mutations) in a gene called SMN1. Genes are the instructions that control a function in the body or a physical trait, like eye color. A person with SMA has two faulty copies of SMN1, one from their father and one from their mother. […] SMA is an inherited disorder that runs in families. If you have a family member who has SMA, it means that your risk of being a carrier is increased. […] Spinal Muscular Atrophy (SMA): An inherited disorder that causes wasting of the muscles and severe weakness. SMA is the leading genetic cause of death in infants.

• #27 Spinal muscular atrophy (SMA) – NHS

  https://www.nhs.uk/conditions/spinal-muscular-atrophy-sma/

  Most types of spinal muscular atrophy (SMA) are caused by an altered gene called SMN1 being passed on to a child by their parents (inherited). […] The parents do not usually have SMA themselves, which is known as „carrying” the gene. In most cases, SMA can only be passed on if both parents carry the altered gene. […] If both parents carry the altered gene, there’s a: 1 in 4 (25%) chance their child will have SMA, 2 in 4 (50%) chance their child will carry the altered gene, but will not have SMA, 1 in 4 (25%) chance their child will not carry the altered gene or have SMA. […] The chances of a child inheriting SMA can be different for some rarer types of SMA. Some rarer types are not passed on at all.

• #28 Spinal Muscular Atrophy | Biogen

  https://www.biogen.com/disease-areas/spinal-muscular-atrophy.html

  SMA is a rare, genetic disease that causes progressive muscle weakness. […] SMA is a leading genetic cause of death for infants and toddlers, and is marked by progressive muscle weakness and atrophy that can take away a persons ability to walk, eat, and ultimately, breathe. […] Around 1 in every 40-50 people globally are carriers of the gene that causes SMA. […] SMA affects approximately one in every 10,000 births worldwide. […] If left untreated, the majority of infants with the most severe form of SMA die within two years.

• #29 Spinal Muscular Atrophy: Causes, Symptoms & Treatments – BuzzRx

  https://www.buzzrx.com/blog/spinal-muscular-atrophy

  Spinal muscular atrophy types 0 through 4 are caused by mutations (changes in the DNA sequence or genetic flaws) in a gene called the survival motor neuron 1 (SMN1 gene) that is located on chromosome 5. This gene is responsible for making the SMN protein. In people with a mutated gene, there is not enough SMN protein. This lack of SMN protein leads to problems with voluntary skeletal muscles receiving nerve signals. […] Having multiple copies of the SMN2 gene is usually associated with less severe symptoms of the condition and the development of the disorder later in life. […] Spinal muscular atrophy (SMA) is an inherited disorder that runs in families. Having a family member with SMA is, therefore, a risk factor for the disorder. […] SMA is more common in Caucasians compared to other races.

• #30 Spinal muscular atrophy (SMA) – Muscular Dystrophy UK

  https://www.musculardystrophyuk.org/conditions/a-z/spinal-muscular-atrophy-sma/

  Spinal Muscular Atrophy (SMA) is a rare, genetically inherited neuromuscular condition. […] All types of 5q SMA affect the nerve cells called lower motor neurons. These are found within the spinal cord and transmit signals to muscles. […] Most people have two copies of the SMN1 gene. People with 5q SMA have two faulty copies of the SMN1 gene, which means they are unable to produce enough SMN protein to have healthy lower motor neurons. […] A second gene also has a role in producing SMN protein. This is the Survival Motor Neuron 2 gene (SMN2), sometimes referred to as the SMA back-up gene. […] 5q SMA is passed from parents to their children through faulty SMN1 genes. It usually follows an autosomal, recessive pattern of inheritance. […] In around 2% of cases of SMA, the mutation is new in the affected person, most likely due to an error in making the egg or sperm cell from which they were conceived. This is called a de novo mutation.

• #31 Spinal muscular atrophy – Wikipedia

  https://en.wikipedia.org/wiki/Spinal_muscular_atrophy

  Spinal muscular atrophy is caused by a genetic mutation in the SMN1 gene. […] The SMN1 gene is mutated in such a way that it is unable to correctly code the SMN protein due to either a deletion occurring at exon 7 or to other point mutations. […] The severity of SMA symptoms is broadly related to how well the remaining SMN2 genes can make up for the loss of function of SMN1. […] Spinal muscular atrophy has an autosomal recessive pattern of inheritance. […] SMA seems to appear de novo (i.e., without any hereditary causes) in around 2-4% of cases. […] The overall prevalence of SMA, of all types and across all ethnic groups, is in the range of 1 per 10,000 individuals; the gene frequency is around 1:100, therefore, approximately one in 50 persons are carriers.

• #32 Spinal Muscular Atrophy | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/spinal-muscular-atrophy

  Spinal muscular atrophy (SMA) refers to a group of hereditary diseases which affect motor neurons. The most common form of SMA is caused by changes in a gene known as the survival motor neuron gene 1 (SMN1). There is a gene very similar to SMN1 called SMN2, which may be present in multiple copies. Although the SMN2 gene makes much less of the SMN protein than the healthy SMN1 gene, extra copies of the SMN2 gene are associated with the less severe forms of SMA (Types II-IV). […] People living with SMA have insufficient levels of the survival motor neuron (SMN) protein, which maintains the health and normal function of motor neurons. Insufficient levels of SMN protein leads to loss of motor neurons in the spinal cord and causes weakness and wasting of the skeletal muscles. The most common form of SMA is caused by the SMN1 gene; however, there are other forms of SMA associated with other genes. […] Less common SMA forms are caused by changes in other genes, including the: IGHMBP2 gene on chromosome 11, MORC2 gene on chromosome 22, UBA1 gene on the X chromosome, DYNC1H1 gene on chromosome 14, BICD2 gene on chromosome 9, TRPV4 on chromosome 12.

• #33 Causes of Spinal Muscular Atrophy | Northwestern Medicine

  https://www.nm.org/conditions-and-care-areas/neurosciences/neuromuscular-program/spinal-muscular-atrophy/causes

  Spinal muscular atrophy (SMA) is a genetic disease, and you can only get it if you inherit the gene for it from both parents. SMA is caused by a mutation in the survival motor neuron gene 1 (SMN1). […] Other rare forms of SMA (non-chromosome 5) are caused by mutations in genes other than SMN1.

• #34 Spinal Muscular Atrophy | National Institute of Neurological Disorders and Stroke

  https://www.ninds.nih.gov/health-information/disorders/spinal-muscular-atrophy

  Spinal muscular atrophy (SMA) refers to a group of hereditary diseases which affect motor neurons. The most common form of SMA is caused by changes in a gene known as the survival motor neuron gene 1 (SMN1). There is a gene very similar to SMN1 called SMN2, which may be present in multiple copies. Although the SMN2 gene makes much less of the SMN protein than the healthy SMN1 gene, extra copies of the SMN2 gene are associated with the less severe forms of SMA (Types II-IV). […] People living with SMA have insufficient levels of the survival motor neuron (SMN) protein, which maintains the health and normal function of motor neurons. Insufficient levels of SMN protein leads to loss of motor neurons in the spinal cord and causes weakness and wasting of the skeletal muscles. The most common form of SMA is caused by the SMN1 gene; however, there are other forms of SMA associated with other genes. […] Less common SMA forms are caused by changes in other genes, including the: IGHMBP2 gene on chromosome 11, MORC2 gene on chromosome 22, UBA1 gene on the X chromosome, DYNC1H1 gene on chromosome 14, BICD2 gene on chromosome 9, TRPV4 on chromosome 12.

• #35 Causes of Spinal Muscular Atrophy | mySMAteam

  https://www.mysmateam.com/resources/causes-of-spinal-muscular-atrophy

  Spinal muscular atrophy (SMA) is a genetic neuromuscular disorder characterized by muscle weakness that worsens over time. […] SMA is an inherited genetic disorder. SMA types 0-4, which account for nearly all cases of SMA, are caused by a mutation (or change) in the survival motor neuron (SMN) genes on both copies of chromosome 5. […] SMN genes tell the body to make SMN protein, which is crucial for the function of motor neurons. […] A genetic variation on both copies of a persons SMN1 gene determines whether a person will have SMA. […] Other SMA types are caused by variations on different genes. […] SMA with respiratory distress (SMARD) is caused by a variant of the immunoglobulin mu DNA binding protein 2 (IGHMBP2) gene. […] Distal SMA can be caused by a genetic change on the Berardinelli-Seip congenital lipodystrophy 2 (BSCL2) or glycyl-tRNA synthetase (GARS1) or receptor accessory protein 1 (REEP1) genes.

• #36 Causes of Spinal Muscular Atrophy | mySMAteam

  https://www.mysmateam.com/resources/causes-of-spinal-muscular-atrophy

  According to Muscular Dystrophy Association, Kennedy disease, also known as X-linked spinal and bulbar muscular atrophy, primarily affects men and is caused by a variation in the androgen receptor (AR) gene on the X chromosome. […] SMA with progressive myoclonic epilepsy, or SMA-PME, is the result of a variation on the N-acylsphingosine amidohydrolase 1 (ASAH1) gene. […] SMA with lower extremity predominance (SMA-LED) can be caused by changes on the dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) or BICD cargo adaptor 2 (BICD2) genes. […] X-linked infantile SMA (XL-SMA) primarily affects males and results from a variation in the ubiquitin-like modifier activating enzyme 1 (UBA1) gene on the X chromosome. […] Nearly all cases of SMA are recessive meaning a child must inherit an altered gene from both parents to develop SMA. […] A few types of SMA, including distal SMA and SMA-LED, are inherited from one parent instead of both.

• #37 Causes of Spinal Muscular Atrophy | mySMAteam

  https://www.mysmateam.com/resources/causes-of-spinal-muscular-atrophy

  According to Muscular Dystrophy Association, Kennedy disease, also known as X-linked spinal and bulbar muscular atrophy, primarily affects men and is caused by a variation in the androgen receptor (AR) gene on the X chromosome. […] SMA with progressive myoclonic epilepsy, or SMA-PME, is the result of a variation on the N-acylsphingosine amidohydrolase 1 (ASAH1) gene. […] SMA with lower extremity predominance (SMA-LED) can be caused by changes on the dynein cytoplasmic 1 heavy chain 1 (DYNC1H1) or BICD cargo adaptor 2 (BICD2) genes. […] X-linked infantile SMA (XL-SMA) primarily affects males and results from a variation in the ubiquitin-like modifier activating enzyme 1 (UBA1) gene on the X chromosome. […] Nearly all cases of SMA are recessive meaning a child must inherit an altered gene from both parents to develop SMA. […] A few types of SMA, including distal SMA and SMA-LED, are inherited from one parent instead of both.

• #38 About Spinal Muscular Atrophy

  https://www.genome.gov/Genetic-Disorders/Spinal-Muscular-Atrophy

  Spinal muscular atrophy (SMA) is the second leading cause of neuromuscular disease. It is usually inherited as an autosomal recessive trait (a person must get the defective gene from both parents to be affected). […] Gene alterations (mutations) in the SMN1 and VAPB genes cause SMA. […] SMA types 0, I, II, III, and IV are inherited in an autosomal recessive pattern in families. In autosomal recessive inheritance, a person who has SMA has inherited two altered (mutated) copies of the SMN1 gene from his or her parents. […] Finkel type SMA is inherited in an autosomal dominant pattern. This means that the person has one copy of the altered gene in each cell that causes the disorder.

• #39 Spinal Muscular Atrophy Pathophysiology | mySMAteam

  https://www.mysmateam.com/resources/spinal-muscular-atrophy-pathophysiology

  The term pathophysiology refers to the abnormalities in the body that underlie or cause a disease or condition. For example, in spinal muscular atrophy (SMA), a genetic neuromuscular disorder, the pathophysiology is influenced primarily by genetic or hereditary factors. These genetic abnormalities cause the degeneration of motor nerves in the spinal cord and lower brain stem. […] SMA is caused by inherited genetic factors (genes passed from generation to generation), which is why SMA tends to run in families. The biggest risk factor for developing SMA is mutations of the SMN1 gene. This gene codes for a protein called the survival motor neuron (SMN) protein. SMN proteins play a critical role in the health and function of the nerves that control muscles responsible for movement, especially in the torso, arms, and legs. When the SMN1 gene is mutated, the body does not make enough of the SMN protein. When the nerves and muscles cant communicate with each other, the muscles begin to weaken and waste away. This leads to problems with breathing, swallowing, walking, or sitting up.

• #40 Study explains how a protein deficiency causes spinal muscular atrophy | Brown University

  https://www.brown.edu/news/2016-07-11/sma

  The disease affects one in 10,000 children in Caucasian populations; both copies of the SMN1 gene are defective in patients. […] But about one in 40 people are carriers in that they have one defective and one functional copy of the SMN1 gene. […] Harts team of researchers reported that that reduced levels of the SMN protein disrupt a cellular process called endocytosis, which all cells normally use to recycle and redistribute proteins and membranes. […] Without this specialized neurotransmitter recycling and endocytosis, synaptic vesicles are not recycled fast enough to keep up with nerve and muscle cell activity. […] The process of endocytosis, however, is also exploited by infectious viruses and bacteria. […] Our results suggest that SMN loss perturbs both general and neuron-specific endocytosis.

• #41 Spinal Muscular Atrophy: New Clues to Cause and Treatment | Columbia University Irving Medical Center

  https://www.cuimc.columbia.edu/news/spinal-muscular-atrophy-new-clues-cause-and-treatment

  Spinal muscular atrophy (SMA), a neurodegenerative disease that causes progressive muscle wasting and paralysis, may be partly due to abnormalities in the synapses that connect sensory neurons and motor neurons, according to researchers at Columbia University Irving Medical Center (CUIMC). […] SMA is triggered by mutations in a gene called SMN1 (Survival Motor Neuron 1), causing a deficiency of SMN protein in all cells including spinal motor neurons, which stimulate the body’s muscles to contract. Low levels of this protein lead to the dysfunction and death of motor neurons, beginning as early as infancy and occasionally during adulthood. […] In a 2011 study published in Neuron, Dr. Mentis found the first evidence that abnormalities in the synapses between sensory neurons and spinal motor neurons may contribute to SMA early in the disease process, well before the death of motor neurons.

• #42 Spinal Muscular Atrophy: New Clues to Cause and Treatment | Columbia University Irving Medical Center

  https://www.cuimc.columbia.edu/news/spinal-muscular-atrophy-new-clues-cause-and-treatment

  Using mouse models of SMA, Dr. Mentis and his colleagues demonstrated that SMN deficiency in sensory neurons altered the synapses that connect them to motor neurons. […] This suggests that increasing synaptic activity could alleviate the neuromuscular deficits seen in SMA. […] This study suggests that there may be more than one way to boost the health of motor neurons in patients with SMA, which represents a fundamental change in how we’ve looked at this disease.

• #43 Study explains how a protein deficiency causes spinal muscular atrophy | Brown University

  https://www.brown.edu/news/2016-07-11/sma

  The disease affects one in 10,000 children in Caucasian populations; both copies of the SMN1 gene are defective in patients. […] But about one in 40 people are carriers in that they have one defective and one functional copy of the SMN1 gene. […] Harts team of researchers reported that that reduced levels of the SMN protein disrupt a cellular process called endocytosis, which all cells normally use to recycle and redistribute proteins and membranes. […] Without this specialized neurotransmitter recycling and endocytosis, synaptic vesicles are not recycled fast enough to keep up with nerve and muscle cell activity. […] The process of endocytosis, however, is also exploited by infectious viruses and bacteria. […] Our results suggest that SMN loss perturbs both general and neuron-specific endocytosis.

• #44 Spinal Muscle Atrophy: Practice Essentials, Pathophysiology, Etiology

  https://emedicine.medscape.com/article/1264401-overview

  Patients with SMA have a homozygous deletion of the telomeric SMN gene SMN1, which is found in arm 5q13 (bands q11.2-13.3). This deletion has been demonstrated in as many as 98% of patients with SMA. […] SMN1 encodes the SMN protein, which is part of a multiprotein complex required for the biogenesis of small nuclear ribonucleoproteins. […] The SMN protein is critical to the health and survival of the nerve cells in the spinal cord that are responsible for muscle contraction (motor neurons). […] A second gene also plays a role in producing the SMN protein namely, SMN2, often called the SMA „backup gene.” […] The severity of SMA is inversely related to the number of copies of SMN2. […] The SMN2 gene copy number is related to, but not predictive of, disease severity, and care decisions should not be made on the basis of copy number alone. […] A significant increase in nuclear DNA vulnerability was detected in fetuses with SMA at 12-15 weeks’ gestational age.

• #45 Spinal muscular atrophy | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-022-00380-8

  Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by mutations in SMN1 (encoding survival motor neuron protein (SMN)). Reduced expression of SMN leads to loss of -motor neurons, severe muscle weakness and often early death. […] Improved understanding of the pathogenetic mechanisms of SMA has led to the development of different therapeutic approaches. […] The incidence of SMA and new phenotypes is likely to emerge as newborn screening becomes more widely initiated and treatment is started very early after birth. […] This comprehensive review discusses the evolution over the past 25 years in the understanding of the pathobiology of SMA, genotype-phenotype relationships and treatment strategies. […] The authors discuss SMA as a systemic disease, beyond a motor neuron disorder, and the implications for needing to consider targeting non-neuronal tissues with SMN-enhancing drugs.

• #46 Spinal muscular atrophy | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-022-00380-8

  Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by mutations in SMN1 (encoding survival motor neuron protein (SMN)). Reduced expression of SMN leads to loss of -motor neurons, severe muscle weakness and often early death. […] Improved understanding of the pathogenetic mechanisms of SMA has led to the development of different therapeutic approaches. […] The incidence of SMA and new phenotypes is likely to emerge as newborn screening becomes more widely initiated and treatment is started very early after birth. […] This comprehensive review discusses the evolution over the past 25 years in the understanding of the pathobiology of SMA, genotype-phenotype relationships and treatment strategies. […] The authors discuss SMA as a systemic disease, beyond a motor neuron disorder, and the implications for needing to consider targeting non-neuronal tissues with SMN-enhancing drugs.

• #47 Spinal muscular atrophy | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-022-00380-8

  Nusinersen is the first of the three SMN-enhancing drugs to demonstrate a marked improvement in survival and function when treatment is started shortly after birth, in the presymptomatic or early symptomatic state of SMA. […] This study presents the positive results of nusinersen treatment in patients with early-infantile onset SMA, with improved survival and motor function. […] This study presents the positive results of nusinersen treatment in patients with late-infantile onset SMA, with improved motor function and a favourable safety profile. […] This study of risdiplam in patients with early-infantile onset SMA type 1 demonstrated improved survival and motor function, and a favourable safety profile, and supported gaining regulatory approval for this drug.

• #48 Spinal Muscular Atrophy (SMA)

  https://www.nemours.org/services/spinal-muscular-atrophy-sma.html

  Spinal muscular atrophy (SMA) is a genetic condition that causes muscle weakness and atrophy (when muscles get smaller). […] Until recently, there was no truly effective treatment option for the most severe form of SMA (SMA type 1). But in 2016, researchers had a breakthrough allowing some kids to live longer and reach more developmental milestones. A medication called Nusinersen (or Spinraza) increases the amount of protein the body needs from a missing gene. And that means improvement in kids breathing, motor function and survival.

• #49 Spinal muscular atrophy (SMA) – Types, Causes and Symptoms

  https://www.signsofsma.com/ie/hcp-what-is-spinal-muscular-atrophy

  SMA is a rare, progressive, inherited monogenic disease, characterised by lower motor neuron degeneration and muscle weakness610. […] SMA is caused by an absent or dysfunctional survival motor neuron 1 (SMN1) gene1418. […] The body has a back-up gene, SMN2. However, it is only capable of producing a small amount of functional SMN protein, which is insufficient for motor neuron survival and function6,14,15,17,18. […] SMN protein deficiency leads to irreversible neuronal degeneration and loss of muscle function in SMA5,14,15. […] Loss of motor neurons in SMA is irreversible4,5. […] Fast diagnosis of SMA is vital, as damage that occurs before treatment is irreversible4,5. […] Research suggests early medical intervention provides the most benefit in SMA10,22,28.

• #50 Spinal muscular atrophy | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-022-00380-8

  Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by mutations in SMN1 (encoding survival motor neuron protein (SMN)). Reduced expression of SMN leads to loss of -motor neurons, severe muscle weakness and often early death. […] Improved understanding of the pathogenetic mechanisms of SMA has led to the development of different therapeutic approaches. […] The incidence of SMA and new phenotypes is likely to emerge as newborn screening becomes more widely initiated and treatment is started very early after birth. […] This comprehensive review discusses the evolution over the past 25 years in the understanding of the pathobiology of SMA, genotype-phenotype relationships and treatment strategies. […] The authors discuss SMA as a systemic disease, beyond a motor neuron disorder, and the implications for needing to consider targeting non-neuronal tissues with SMN-enhancing drugs.

• #51 Study explains how a protein deficiency causes spinal muscular atrophy | Brown University

  https://www.brown.edu/news/2016-07-11/sma

  Research that reveals what goes wrong in SMA and suggests that a mild version of the same genetic defect may protect relatives against infection, which could explain why SMA is relatively common disease. […] Scientists and doctors know that the devastating disease spinal muscular atrophy (SMA) arises from a problem with both copies of the SMN1 gene, leading to a lack of the survival motor neuron (SMN) protein. […] A new study implicates a key cellular mechanism as defective in SMA for the first time, providing a new lead for developing future interventions. […] The study also yielded a surprising twist: A mild version of the same defect may also confer resistance to infection in carriers of the disease for whom only one copy of the gene has lost function. […] SMA is the most common genetic cause of infant death in the U.S. and there is no effective treatment or cure.

• #52 Study explains how a protein deficiency causes spinal muscular atrophy | Brown University

  https://www.brown.edu/news/2016-07-11/sma

  While the study shows that reduced SMN disrupts endocytosis, it doesnt explain why. […] For now, this study doesnt provide any proof that being an SMN carrier reduces a persons likelihood of becoming sickened by infections. […] The result may also explain why, even though SMA is a devastating disease, carriers remain relatively common. […] It seems possible that SMA is relatively common because carriers might be protected from infection. […] If carriers are more likely to survive and reproduce, then evolutionary pressure might favor carriers in the long term, as is seen for sickle cell anemia and malaria infection.

• #53 Study explains how a protein deficiency causes spinal muscular atrophy | Brown University

  https://www.brown.edu/news/2016-07-11/sma

  While the study shows that reduced SMN disrupts endocytosis, it doesnt explain why. […] For now, this study doesnt provide any proof that being an SMN carrier reduces a persons likelihood of becoming sickened by infections. […] The result may also explain why, even though SMA is a devastating disease, carriers remain relatively common. […] It seems possible that SMA is relatively common because carriers might be protected from infection. […] If carriers are more likely to survive and reproduce, then evolutionary pressure might favor carriers in the long term, as is seen for sickle cell anemia and malaria infection.

• #54 Spinal muscular atrophy | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-022-00380-8

  Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by mutations in SMN1 (encoding survival motor neuron protein (SMN)). Reduced expression of SMN leads to loss of -motor neurons, severe muscle weakness and often early death. […] Improved understanding of the pathogenetic mechanisms of SMA has led to the development of different therapeutic approaches. […] The incidence of SMA and new phenotypes is likely to emerge as newborn screening becomes more widely initiated and treatment is started very early after birth. […] This comprehensive review discusses the evolution over the past 25 years in the understanding of the pathobiology of SMA, genotype-phenotype relationships and treatment strategies. […] The authors discuss SMA as a systemic disease, beyond a motor neuron disorder, and the implications for needing to consider targeting non-neuronal tissues with SMN-enhancing drugs.

• #55 Spinal muscular atrophy | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-022-00380-8

  Nusinersen is the first of the three SMN-enhancing drugs to demonstrate a marked improvement in survival and function when treatment is started shortly after birth, in the presymptomatic or early symptomatic state of SMA. […] This study presents the positive results of nusinersen treatment in patients with early-infantile onset SMA, with improved survival and motor function. […] This study presents the positive results of nusinersen treatment in patients with late-infantile onset SMA, with improved motor function and a favourable safety profile. […] This study of risdiplam in patients with early-infantile onset SMA type 1 demonstrated improved survival and motor function, and a favourable safety profile, and supported gaining regulatory approval for this drug.

• #56 Spinal muscular atrophy | Nature Reviews Disease Primers

  https://www.nature.com/articles/s41572-022-00380-8

  Spinal muscular atrophy (SMA) is a neurodegenerative disorder caused by mutations in SMN1 (encoding survival motor neuron protein (SMN)). Reduced expression of SMN leads to loss of -motor neurons, severe muscle weakness and often early death. […] Improved understanding of the pathogenetic mechanisms of SMA has led to the development of different therapeutic approaches. […] The incidence of SMA and new phenotypes is likely to emerge as newborn screening becomes more widely initiated and treatment is started very early after birth. […] This comprehensive review discusses the evolution over the past 25 years in the understanding of the pathobiology of SMA, genotype-phenotype relationships and treatment strategies. […] The authors discuss SMA as a systemic disease, beyond a motor neuron disorder, and the implications for needing to consider targeting non-neuronal tissues with SMN-enhancing drugs.

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