Materiały źródłowe

• #1 Spinal Muscular Atrophy: Diagnosis and Management in a New Therapeutic Era

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4293319/

  Spinal muscular atrophy (SMA) describes a group of disorders associated with spinal motor neuron loss. […] Electromyography and muscle biopsy features of denervation were once the basis for diagnosis, but molecular testing for homozygous deletion or mutation of the SMN1 gene allows efficient and specific diagnosis. […] Molecular genetic testing is the standard tool for diagnosis of SMA. […] The homozygous deletion of SMN1 is essentially 100% specific for the diagnosis of SMA, and disease severity is modified by SMN2 copy number. […] Importantly, patients with SMA have homozygous loss of function of both SMN1 copies; genetic testing for homozygous deletion will confirm the disease in 95% of patients irrespective of disease severity. […] If homozygous SMN1 deletion is not evident in a patient with suspected SMA, SMN1 dosage analysis (to look for deletion of 1 copy) and sequencing of the remaining SMN1 gene (to look for a mutation) should be performed. […] At present there are no effective disease-modifying treatments for SMA. […] Nevertheless, precisely designed supportive, rehabilitative, and palliative care can partly reduce the disease burden and alter the natural history.

• #1 Diagnosis – Spinal Muscular Atrophy (SMA) – Diseases | Muscular Dystrophy Association

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

  The first steps in diagnosis of a neuromuscular disease are usually an in-office physical examination and family history, with some simple tests to distinguish spinal muscular atrophy (SMA) from similar conditions (such as muscular dystrophy). Muscle weakness and hypotonia should be the first signs that raise suspicion for SMA in babies. Other signs can help to confirm the diagnosis, such as a history of motor difficulties, loss of motor skills, proximal muscle weakness, hyporeflexia (absence of reflexes), tongue fasciculations (involuntary twitches), and signs for low motor neuron disease. […] A doctor may order a blood test for an enzyme called creatine kinase (CK), which leaks out of muscles that are deteriorating. This is a nonspecific test because CK levels are elevated in many neuromuscular diseases, but its often a useful test. High blood CK levels arent harmful in and of themselves, but they do indicate that muscle damage has occurred. Usually, CK levels are normal in patients diagnosed with SMA type 1 but can be a slightly elevated in patients diagnosed with other types of SMA, such as types 2 and 3. As a result, SMA types 2 and 3 might be confused with other neuromuscular disease, such as Duchenne muscular dystrophy.

• #1 Testing & Diagnosis – Cure SMA

  https://www.curesma.org/testing-diagnosis/

  A spinal muscular atrophy (SMA) diagnosis must be confirmed through genetic testing. SMA is diagnosed after noticing symptoms of SMA, through newborn screening, or via prenatal testing. […] A simple blood draw test can identify an estimated 95% of all SMA cases by testing for deletion or mutation of both SMN1 genes. The other 5% are caused by a rare point mutation on one SMN1 allele and heterozygous deletion on the other SMN1 allele and are not identified by usual SMN1 gene testing. Individuals with a point mutation are identified through further blood testing with gene sequence analysis. […] If a newborn screening result is positive for SMA, follow-up testing is required to confirm the diagnosis. […] Prenatal testing is used to determine if a fetus has inherited a genetic disorder. After consultation with their doctor, some families may choose this type of testing if their child is known to be at risk for SMA.

• #1 Spinal Muscle Atrophy Workup: Laboratory Studies, Imaging Studies, Other Tests

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

  A simple blood test can confirm whether the child has a mutation that causes spinal muscle atrophy (SMA; also known as spinal muscular atrophy). The SMN1 deletion test is recommended as the first diagnostic step for a patient suspected of having SMA. The deletion status can be tested by using polymerase chain reaction (PCR) to determine if both copies of SMN1 exon 7 are absent, a finding that is noted in 95% of affected individuals. […] If the survival motor neuron (SMN) gene test is positive, the diagnosis is confirmed. However, 5% of children with the symptoms of SMA can have a negative SMN gene test and may require additional diagnostic testing. These tests can include electromyography (EMG), a nerve conduction study (NCS), or muscle biopsy and additional blood tests to help rule out other forms of muscle disease.

• #1 Spinal muscular atrophy (5qSMA): best practice of diagnostics, newborn screening and therapy

  https://www.degruyter.com/document/doi/10.1515/medgen-2020-2033/html?lang=en

  A PCR based approach for the detection of a homozygous deletion of exons 7 and 8 of SMN1 may lead to a quick diagnosis in certain situations (e.g. prenatal diagnosis) but it does not replace the exact quantification of SMN1 and SMN2 copies. […] For the interpretation of the MLPA results and the exact quantification of SMN1 and SMN2 copy numbers, exact knowledge of the genotype of the control DNA is necessary. […] If a homozygous deletion of SMN1 exons 7 and 8 is detected, the diagnosis of 5q-SMA is confirmed. […] A homozygous deletion of SMN1 exon 7 only also confirms 5q-SMA. […] In case a patient shows two or more SMN1 copies by MLPA, the diagnosis of 5q-SMA is almost excluded and differential diagnoses should be considered. […] If a patient suspected of having 5q-SMA shows only one SMN1 copy, a pathogenic SNV might be present on the second allele.

• #1 Spinal muscular atrophy (5qSMA): best practice of diagnostics, newborn screening and therapy

  https://www.degruyter.com/document/doi/10.1515/medgen-2020-2033/html?lang=en

  A homozygous deletion of SMN2 has no impact on the individual, and instead excludes the diagnosis of SMA. […] The exact quantification of the SMN2 copy number in patients with a homozygous SMN1 deletion is relevant for inclusion in therapy programmes, choice of therapy and the monitoring of their outcome. […] Since the introduction of the therapies, it has become evident that an early pre-symptomatic treatment of patients is crucial for the therapeutic outcome. […] We expect that the NBS for 5q-SMA will be implemented in Germany by the end of 2020 or at the latest early 2021. […] Although the current therapeutic approaches are highly promising, SMA cannot be regarded as a fully treatable condition yet; too little is known about the long-term effects of the different therapies.

• #1 SMNDX – Overview: Spinal Muscular Atrophy Diagnostic Assay, Deletion/Duplication Analysis, Varies

  https://www.mayocliniclabs.com/test-catalog/Overview/65575

  SMA is most commonly caused by a homozygous deletion of exon 7 in SMN1. […] The severity of a patient’s disease is associated with the number of copies of SMN2 that are present and 3 or more SMN2 copies are associated with a milder SMA phenotype. […] Point mutations are undetectable by this assay. Nor can this assay definitively discriminate between 2 copies of survival motor neuron 1 (SMN1) on the same chromosome versus 2 copies on separate chromosomes for patients of most ancestries. […] Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

• #1 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). […] As we learn more about SMA and develop new treatments, diagnosis and classification of SMA is involving to include both clinical symptoms and genetic information. […] A blood test is available to look for mutations or deletions of the SMN1 gene. This test identifies at least 95% of SMA Types I, II, and III, and may reveal if a person is a carrier for SMA. […] If the SMN1 gene is normal or the individual’s history and examination are not typical of SMA, other diagnostic tests include: Electromyography to record the electrical activity of the muscles during contraction and at rest, Nerve conduction velocity studies to measure the nerve’s ability to send an electrical signal, Muscle biopsy may be used to diagnose other conditions with symptoms similar to SMA.

• #1 Diagnosis – Spinal Muscular Atrophy (SMA) – Diseases | Muscular Dystrophy Association

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

  A doctor probably will recommend genetic testing if SMA is suspected because this is the least invasive and most accurate way to diagnose chromosome 5-related SMA (types 1-4). Genetic testing requires only a blood sample. However, it has implications for the whole family that must be considered. Reliability and specificity of genetic tests are improving, and the number of tests available is expanding rapidly as knowledge and technology improve. […] In rare cases, doctors may order a muscle biopsy, which involves taking a small sample of muscle tissue, usually from the thigh, and looking at it under a microscope. […] Other tests sometimes used to diagnose SMA include one that measures nerve conduction velocity the speed with which signals travel along nerves and one that measures the electrical activity in muscle, called an electromyogram, or EMG. Nerve conduction velocity tests involve sensations that feel like mild electric shocks, and EMGs require that short needles be inserted in the muscles.

• #1 Spinal Muscular Atrophy Workup: Laboratory Studies, Other Tests, Procedures

  https://emedicine.medscape.com/article/1181436-workup

  Electrophysiologic studies are useful in differentiating the spinal muscular atrophies from other neurogenic and myopathic diseases. […] Muscle biopsy may necessary to differentiate spinal muscular atrophies from other neuromuscular disorders if genetic analysis is unrevealing. […] Histologic findings depend on the stage and progression of disease. Initial changes include atrophy of muscle fibers with compensatory hypertrophy. This results in groups of large and small fibers (fiber-type grouping). […] Classic histologic findings include the following: Degeneration and loss of spinal motor neurons with a neurogenic pattern of muscle morphology.

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

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

  These newer treatments may be particularly effective if started early, even before symptoms of SMA appear. Given the availability of these treatments, theres now routine screening of newborns for SMA in the United States. […] SMA is an inherited condition, so its not typically preventable. But genetic testing can help you understand your odds of having a biological child with SMA. […] The prognosis (outlook) for someone with SMA varies based on the subtype. Your healthcare team can give you a better idea of what to expect based on your or your childs situation. […] Its important to note that disease-modifying and gene replacement therapies have been proven to substantially improve survival in SMA type 1. Your healthcare team will be able to give you a better idea of what to expect.

• #1 Spinal Muscular Atrophy Workup: Laboratory Studies, Other Tests, Procedures

  https://emedicine.medscape.com/article/1181436-workup

  The creatine kinase (CK) level is typically normal in SMA type I and normal or slightly elevated in the other types. […] Both prenatal and postnatal tests are now commercially available. […] Homozygous SMN1 gene deletion is 95% sensitive and nearly 100% specific for the diagnosis of SMA. In patients with suspected disease and no gene deletion, SMN1 copy testing with sequencing of coding regions of SMN1 copy (if present) is suggested. […] Molecular testing for homozygous deletion or mutation of the SMN1 gene allows efficient and specific diagnosis. […] The 1992 ISMAC found that the accuracy of prenatal prediction by means of chorionic villi sampling and amniocentesis was 88-99%. […] Caution should be exercised when prenatal prediction is done in the presence of atypical features (see SMA variants in Physical) because these clinical variations may represent other pathogenic processes.

• #1 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. […] Carrier screening for SMA can tell you whether you are at risk of having a baby with SMA, but it cannot tell you with 100% certainty. Also, if screening shows that both parents are carriers, the results cannot tell you how severe the disease may be if one of your children inherits it.

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

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

  Carrier screening results for SMA are reported as the number of healthy copies of SMN1 a person has: If you have one healthy copy of SMN1, it means the other copy is faulty and you are a carrier. You could pass the faulty copy of the SMN1 gene to your child. […] If your partner also is a carrier, your risk of having a child with SMA is 1 in 4. Your risk of having a child who is a carrier is 1 in 2. […] All women who are thinking about getting pregnant or who are already pregnant should be offered carrier screening for SMA. […] Carrier screening can be done either before pregnancy or during pregnancy. Having carrier screening before you get pregnant gives you more options than having it during pregnancy. […] If you find out that you and your partner are carriers before pregnancy, you have the following choices: You can get pregnant and then have amniocentesis or chorionic villus sampling (CVS) to see if the fetus has SMA. […] Your test results cannot be shared without your consent.

• #1 What Tests are Used for a Spinal Muscular Atrophy(SMA) Diagnosis?Share to Facebookprint pageBookmark for latercaret iconFollow us on facebookFollow us on instagramFollow us on facebookFollow us on linkedincaret icon

  https://spinalmuscularatrophy.net/diagnosis

  The test uses a blood sample to check if the SMN1 gene is present. […] Unless there are previous cases of SMA in the family, diagnosis usually begins after symptoms appear. […] Early symptoms of SMA are similar to other neuromuscular disorders. Families may go through many referrals and tests before SMA is suspected. Once your doctor suspects SMA, they will order genetic testing through a blood sample. […] Newborn screening identifies conditions at birth where early diagnosis improve long-term health. This allows babies to begin treatment before symptoms appear. […] Newly approved disease-modifying treatments for SMA are more effective when started earlier. Screening newborns for SMA helps them start these treatments as early as possible. […] Prenatal testing can determine if an unborn baby has inherited SMA. This test is done if the child is at risk for SMA.

• #1 Spinal Muscular Atrophy | Baby’s First Test | Newborn Screening | Baby Health

  https://www.babysfirsttest.org/newborn-screening/conditions/spinal-muscular-atrophy

  Spinal muscular atrophy (SMA) is a group of inherited conditions that affect the motor neurons of the spinal cord. […] Early detection and treatment of SMA is important since studies suggest that therapy is most effective when started in the first few months of life. […] Follow-up testing must be conducted as soon as possible to determine whether or not your baby has the condition. […] People affected by SMA have a change (mutation) in each copy of the SMN1 gene. […] The SMN2 copy number modifies the severity of SMA. […] Although there is currently no cure for spinal muscular atrophy (SMA), treatments are available to manage associated symptoms and improve quality of life. […] Regardless of what type of treatment is chosen, it is important that individuals with SMA begin therapy as soon after diagnosis as possible. Early treatment is the only way to prevent motor neuron loss.

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

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

  Several treatments have been developed for SMA that preserve motor neurons, improve muscle function, and extend lives, but these are not cures. […] FDA-approved treatments for SMA include: Nusinersen (Spinraza) increases production of the SMN protein and is approved to treat children and adults with SMA. […] Onasemnogene abeparovec-xioi (Zolgensma) is a gene therapy for children less than two years old who have infantile-onset SMA (Type I). […] Risdiplam (Evrysdi) is an orally administered drug to treat people age two months and older. […] It is important the people with SMA get proper nutrition to help them maintain weight and promote muscle function. […] Clinical research with human study participants helps researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.

• #1 Spinal Muscle Atrophy Workup: Laboratory Studies, Imaging Studies, Other Tests

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

  Diagnostic delays are common in SMA. A systematic review of the literature conducted to diagnose diagnostic delay reported both age of onset and age at confirmed diagnosis; the delay to diagnosis ranged from months to years. […] Earlier identification of newborns with SMA will also allow infants to begin treatment even before showing symptoms, when research in human and mouse models suggests it may be most effective.

• #1 Diagnosing SMA

  https://care.togetherinsma.eu/en/home/sma-in-infants-and-children/diagnosing-sma.html

  Your best chance of preventing disease progression is to have the condition diagnosed as soon as possible. […] The first thing a doctor may notice in a baby with SMA is floppiness or decreased muscle tone (hypotonia). […] Symptoms may include progressive muscle weakness, floppiness, and muscle wasting (atrophy). […] Each child may experience symptoms differently, and the disease is divided into types based on age of onset and functional ability. […] Because each child shows signs and symptoms at different ages and with different severity, an initial diagnosis can be delayed. […] Although newborn screening is not yet standard practice, time to diagnosis is critical. Earlier diagnosis may help improve outcomes for children with spinal muscular atrophy.

• #1 Limitations of NGS in Spinal Muscular Atrophy (SMA) Testing

  https://3billion.io/blog/limitation-of-ngs-spinal-muscular-atrophy-sma-genetic-testing

  Owing to the combined technology of massive parallel sequencing and bioinformatic analysis in a short time, the next-generation sequencing (NGS), has been widely used for disease diagnosis, prognosis, therapeutic decision, and follow-up of patients replacing the traditional genetic testing such as single gene testing using Sanger sequencing. […] The limitations of exome sequencing and genome sequencing have already been described, but here the limitation of NGS will be mainly focused by discussing how difficult it is to achieve the molecular diagnosis of spinal muscular atrophy with NGS. […] Early and accurate diagnosis of SMA is extremely critical compared to other rare genetic disorders, as a couple of treatment options are available, one of which is the newly approved Zolgensma that treats SMA patients with improved prognosis as a one-shot gene therapy.

• #2 Spinal Muscular Atrophy: The Past, Present, and Future of Diagnosis and Treatment

  https://www.mdpi.com/1422-0067/24/15/11939

  Spinal muscular atrophy (SMA) is a lower motor neuron disease with autosomal recessive inheritance. […] The gene responsible for SMA, SMN1, was identified in 1995. […] Before the identification of responsible gene for SMA, SMN1, histological findings of the biopsied muscles were very important for the diagnosis of SMA. […] However, after the discovery of the SMN1 gene, diagnostic procedures have been completely changed. […] Instead, SMA has been diagnosed based on the genetic testing of SMN1 deletion or mutation. […] Following the great success of these trials, population-based newborn screening programs for SMA (more precisely, SMN1-deleted SMA) have been increasingly implemented worldwide. […] Early detection by newborn screening and early treatment with new drugs are expected to soon become the standards in the field of SMA.

• #2 Spinal Muscular Atrophy: How It’s Diagnosed

  https://www.webmd.com/brain/spinal-muscular-atrophy-diagnosis

  Spinal muscular atrophy is a disease that is usually seen in babies and children. It makes their muscles weak and hard to move. It’s a rare illness that is passed down in families. […] A doctor might want to test your child for SMA if they show symptoms like: Weak or floppy arms or legs, Delay in normal milestones like holding up their head, rolling over, sitting up, standing, or walking, Trouble breathing, Issues eating and swallowing, Tongue twitching, Curved spine (scoliosis). […] So, to diagnose SMA, your doctor will likely do several things. […] The first step is a general physical exam. Your doctor will look for muscle weakness and any other signs of SMA. They’ll also ask questions about all the symptoms your child has. You’ll also be asked if anyone else in your family has problems with muscles and nerves, or if they have SMA.

• #2 Spinal Muscular Atrophy Workup: Laboratory Studies, Other Tests, Procedures

  https://emedicine.medscape.com/article/1181436-workup

  The creatine kinase (CK) level is typically normal in SMA type I and normal or slightly elevated in the other types. […] Both prenatal and postnatal tests are now commercially available. […] Homozygous SMN1 gene deletion is 95% sensitive and nearly 100% specific for the diagnosis of SMA. In patients with suspected disease and no gene deletion, SMN1 copy testing with sequencing of coding regions of SMN1 copy (if present) is suggested. […] Molecular testing for homozygous deletion or mutation of the SMN1 gene allows efficient and specific diagnosis. […] The 1992 ISMAC found that the accuracy of prenatal prediction by means of chorionic villi sampling and amniocentesis was 88-99%. […] Caution should be exercised when prenatal prediction is done in the presence of atypical features (see SMA variants in Physical) because these clinical variations may represent other pathogenic processes.

• #2 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). […] As we learn more about SMA and develop new treatments, diagnosis and classification of SMA is involving to include both clinical symptoms and genetic information. […] A blood test is available to look for mutations or deletions of the SMN1 gene. This test identifies at least 95% of SMA Types I, II, and III, and may reveal if a person is a carrier for SMA. […] If the SMN1 gene is normal or the individual’s history and examination are not typical of SMA, other diagnostic tests include: Electromyography to record the electrical activity of the muscles during contraction and at rest, Nerve conduction velocity studies to measure the nerve’s ability to send an electrical signal, Muscle biopsy may be used to diagnose other conditions with symptoms similar to SMA.

• #2 Spinal muscular atrophy (5qSMA): best practice of diagnostics, newborn screening and therapy

  https://www.degruyter.com/document/doi/10.1515/medgen-2020-2033/html?lang=en

  Proximal spinal muscular atrophy (SMA) is an autosomal-recessive inherited neuromuscular disorder caused by the degeneration of alpha motor neurons in the anterior horn of the spinal cord. […] Since the discovery of the underlying genetic defect 25 years ago, both the diagnostics of SMA and its treatment have undergone constant and in recent times rapid improvements. […] This article aims at summarising the current state of SMA diagnostics, treatment and perspectives for this disorder and offering best practice testing guidelines to diagnostic labs. […] In case 5q-SMA is suspected in a patient, molecular genetic diagnostics should be initiated immediately. […] MLPA is the golden standard for the determination of the SMN1 and SMN2 copy number and carried out by nearly all diagnostic labs as shown in the annual European Molecular Quality Network (EMQN) schemes.

• #2 Limitations of NGS in Spinal Muscular Atrophy (SMA) Testing

  https://3billion.io/blog/limitation-of-ngs-spinal-muscular-atrophy-sma-genetic-testing

  The molecular diagnosis of SMA requires the identification of two pathogenic variants that cause loss of SMN1. […] Therefore, genetic testing for patients who are suspected of SMA should first be tested using non-NGS technology such as long-range PCR that specifically targets SMN1 or long-read sequencing. […] In practice, multiplex ligation-dependent probe amplification (MLPA), which is sequencing independent, is the most common technique that can reliably detect SMN1 deletion, while long-range PCR coupled with Sanger sequencing can reliably detect any heterozygous SNV/INDELs that might be present. […] Although it has limitations, it is not impossible to utilize NGS to diagnose SMA. […] Therefore, SMN1 deletion can be detected by monitoring a loss of SMN1 exon 7 coverage. […] Nonetheless, for patients suspected of SMA, it is best practice to first perform MLPA-based tests for SMN1 deletion, then perform targeted gene tests for SMN1 if MLPA results in negative or inconclusive.

• #2 Spinal Muscular Atrophy: Diagnosis and Management in a New Therapeutic Era

  https://pmc.ncbi.nlm.nih.gov/articles/PMC4293319/

  Spinal muscular atrophy (SMA) describes a group of disorders associated with spinal motor neuron loss. […] Electromyography and muscle biopsy features of denervation were once the basis for diagnosis, but molecular testing for homozygous deletion or mutation of the SMN1 gene allows efficient and specific diagnosis. […] Molecular genetic testing is the standard tool for diagnosis of SMA. […] The homozygous deletion of SMN1 is essentially 100% specific for the diagnosis of SMA, and disease severity is modified by SMN2 copy number. […] Importantly, patients with SMA have homozygous loss of function of both SMN1 copies; genetic testing for homozygous deletion will confirm the disease in 95% of patients irrespective of disease severity. […] If homozygous SMN1 deletion is not evident in a patient with suspected SMA, SMN1 dosage analysis (to look for deletion of 1 copy) and sequencing of the remaining SMN1 gene (to look for a mutation) should be performed. […] At present there are no effective disease-modifying treatments for SMA. […] Nevertheless, precisely designed supportive, rehabilitative, and palliative care can partly reduce the disease burden and alter the natural history.

• #2 SMNDX – Overview: Spinal Muscular Atrophy Diagnostic Assay, Deletion/Duplication Analysis, Varies

  https://www.mayocliniclabs.com/test-catalog/Overview/65575

  SMA is most commonly caused by a homozygous deletion of exon 7 in SMN1. […] The severity of a patient’s disease is associated with the number of copies of SMN2 that are present and 3 or more SMN2 copies are associated with a milder SMA phenotype. […] Point mutations are undetectable by this assay. Nor can this assay definitively discriminate between 2 copies of survival motor neuron 1 (SMN1) on the same chromosome versus 2 copies on separate chromosomes for patients of most ancestries. […] Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in our interpretation of results may occur if information given is inaccurate or incomplete.

• #2 SMA Carrier Screening | Women’s Health | HCP | GenPath Diagnostics

  https://www.genpathdiagnostics.com/hcp/womens-health/carrier-screening/sma-carrier-screening/

  Spinal Muscular Atrophy (SMA) is a disease that causes abnormally functioning motor neurons, which control voluntary movements such as walking, talking, and swallowing. […] SMA is caused by changes in the survival motor neuron 1, or SMN1, gene. […] SMA is inherited in an autosomal recessive manner. In most cases, both parents must be carriers of the condition in order to have a child with SMA. […] If one parent is found to be a carrier, screening is recommended for their partner. […] Yes. Although testing for SMA is very accurate, there are limitations. […] This test will not be able to identify these carriers. […] This is why the risk of being a carrier in individuals with two or three copies of the SMN1 gene is reduced but not eliminated. […] Since SMA is a common and severe genetic condition, ACMG and ACOG recommend that SMA carrier testing be offered to all couples prior to conception or early in pregnancy. […] Yes. Prenatal testing by chorionic villi sampling or amniocentesis can be performed to determine whether or not a fetus is affected with SMA.

• #2 Spinal Muscular Atrophy

  https://practicalneurology.com/articles/2019-aug-july/spinal-muscular-atrophy

  Spinal muscular atrophy (SMA) comprises a diverse group of inherited neuromuscular disorders characterized by spinal cord alpha motor neuron degeneration with resultant progressive weakness and atrophy. […] Clinical suspicion for SMA should arise in hypotonic infants and individuals of any age with a symmetric predominantly proximal pattern of weakness. Genetic testing that includes quantitative analysis of SMN1; identification of homozygous deletions; and SMN2, for which copy number has important prognostic and therapeutic implications is the diagnostic standard. There are several methods for quantitative analysis including multiplex ligation-dependent probe amplification (MLPA), quantitative polymerase chain reaction (qPCR), or NGS. […] The absence of both full SMN1 copies confirms diagnosis of SMA in about 96% of people. The remaining 4% represents compound heterozygotes with an SMN1 deletion of 1 allele and an intragenic missense or frameshift mutation of the other. Thus, if only 1 SMN1 copy is found, sequencing of the gene is required to identify the intragenic mutations.

• #2 About SMA for Healthcare Providers – Cure SMA

  https://www.curesma.org/about-sma-for-hcps/

  A simple blood test can confirm whether an individual has a mutation that causes SMA. If it is a positive gene test, then the diagnosis is confirmed. Although, 5% of people with the symptoms of SMA can have a negative SMN gene test and may require additional diagnostic testing. These tests can include an electromyography study (EMG), nerve conduction study (NCS), and/or a muscle biopsy and blood tests to help rule out other forms of muscle disease. If a positive test is confirmed, then it is important for individuals and/or families to discuss these results with their doctor or genetic counselor.

• #2 Spinal Muscular Atrophy (SMA): Diagnosis & Treatment | NewYork-Presbyterian

  https://www.nyp.org/pediatrics/orthopedics/spinal-muscular-atrophy-sma/treatment

  How is Spinal Muscular Atrophy (SMA) Diagnosed? Diagnosis Symptoms of spinal muscular atrophy (SMA) may be similar to other serious conditions such as muscular dystrophy. As a result, its important to get a proper workup if you or your physician suspect your child might have SMA. In New York State, SMA is part of the newborn screening. Some methods used to diagnose SMA include: […] Blood tests. A simple genetic test identifies at least 95% of SMA cases. It may also reveal whether your child is a carrier. […] Electromyography. This procedure records the electrical activity of muscles during contraction and at rest. […] Nerve conduction velocity studies. These measure the nerves ability to send an electrical signal. […] Muscle biopsy. During this procedure, a small sample of muscle and nerve tissue is surgically removed and examined to see if it shows signs of SMA.

• #2 Spinal Muscular Atrophy Workup: Laboratory Studies, Other Tests, Procedures

  https://emedicine.medscape.com/article/1181436-workup

  Electrophysiologic studies are useful in differentiating the spinal muscular atrophies from other neurogenic and myopathic diseases. […] Muscle biopsy may necessary to differentiate spinal muscular atrophies from other neuromuscular disorders if genetic analysis is unrevealing. […] Histologic findings depend on the stage and progression of disease. Initial changes include atrophy of muscle fibers with compensatory hypertrophy. This results in groups of large and small fibers (fiber-type grouping). […] Classic histologic findings include the following: Degeneration and loss of spinal motor neurons with a neurogenic pattern of muscle morphology.

• #2 Spinal Muscular Atrophy: How It’s Diagnosed

  https://www.webmd.com/brain/spinal-muscular-atrophy-diagnosis

  A simple blood test can check for SMA. Changes or defects in the SMN (survival motor neuron) gene are found in more than 95% of people who have this disorder. […] If that blood test shows one of those gene issues, your doctor will order more tests to confirm that SMA is there. […] This test measures how well muscles are working. […] You might get this along with an EMG. Nerve conduction studies measure how fast signals travel along nerves. […] This blood test looks for an enzyme called creatine kinase. It’s found when muscles are damaged. […] In the past, this was the main way SMA was diagnosed. Now, it’s used only in rare cases if other tests arent able to confirm the disease.

• #2 Spinal Muscular Atrophy | Doctor

  https://patient.info/doctor/spinal-muscular-atrophy-pro

  Diagnosing spinal muscular atrophy (investigations) […] Electromyography and muscle biopsy features of denervation were once the basis for diagnosis, but molecular testing for homozygous deletion or mutation of the SMN1 gene allows efficient and specific diagnosis. […] Genetic testing can be carried out prenatally or postnatally. […] Histology shows muscle fibre atrophy and can help to differentiate from other neuromuscular disorders.

• #2 Spinal Muscle Atrophy Workup: Laboratory Studies, Imaging Studies, Other Tests

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

  Diagnostic delays are common in SMA. A systematic review of the literature conducted to diagnose diagnostic delay reported both age of onset and age at confirmed diagnosis; the delay to diagnosis ranged from months to years. […] Earlier identification of newborns with SMA will also allow infants to begin treatment even before showing symptoms, when research in human and mouse models suggests it may be most effective.

• #2 Spinal muscular atrophy – Wikipedia

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

  Spinal muscular atrophy is diagnosed using genetic testing that detects homozygous deletion of the SMN1 gene in over 95% of cases, and a compound SMN1 mutation in the remaining patients. Genetic testing is usually carried out using a blood sample, and MLPA is one of more frequently used genetic testing techniques, as it also allows establishing the number of SMN2 gene copies, which has clinical importance. […] Early diagnosis of SMA, at the asymptomatic stage of the disease, allows to introduce causative therapies early enough to prevent the manifestation of symptoms. […] Prenatal testing for SMA is possible through chorionic villus sampling, cell-free fetal DNA analysis and other methods. […] Routine newborn screening for SMA is becoming increasingly commonplace in developed countries, given the availability of causative treatments that are most effective at the asymptomatic stage of the disease. In 2018, newborn screening for SMA was added to the US list of recommended newborn screening tests and as of April 2020 it has been adopted in 39 US states. As of February 2023, SMA screening has been incorporated in national newborn screening programmes in around 15 countries and pilot projects are under way in further countries.

• #2 Spinal muscular atrophy (SMA) diagnosis and testing | SMA News TodayEnvelope icon

  https://smanewstoday.com/spinal-muscular-atrophy-diagnosis/

  Genetic testing for spinal muscular atrophy (SMA) is a medical laboratory technique that checks whether a person carries mutations that are known to cause SMA. Genetic testing also can be used to identify SMA carriers — people who will not develop SMA themselves, but who carry the disease-causing mutation and may pass it on to their biological children. […] Genetic disorders such as spinal muscular atrophy (SMA) can be detected during pregnancy by taking a small sample of cells from the fetus and performing genetic testing to look for disease-causing mutations. The most common strategies used to obtain fetal cells for this testing are chorionic villus sampling (CVS), which collects a sample of cells from the placenta, and amniocentesis, which takes a sample of the fluid surrounding the developing fetus.

• #2 Spinal muscular atrophy (SMA) – NHS

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

  If a doctor thinks your child could have spinal muscular atrophy (SMA), a blood test can be used to confirm the diagnosis. […] If you’re at risk of having a child with SMA, a GP may refer you to a genetic counsellor to discuss the risks and options. […] Tests are available before, during and after pregnancy to see if you carry the altered gene or to confirm a diagnosis. […] These tests may include: a genetic blood test to see if you carry the altered gene, chorionic villus sampling (CVS) or amniocentesis tests during pregnancy to check if your baby has SMA, a blood test after your baby is born.

• #2 Spinal Muscular Atrophy | GenPath Diagnostics

  https://www.genpathdiagnostics.com/patients/womens-health/carrier-screening/spinal-muscular-atrophy/

  Spinal Muscular Atrophy (SMA) is a disease that causes motor neurons, which control voluntary movements such as walking, talking, and swallowing, to function abnormally. […] SMA leads to progressive muscle weakness and atrophy, especially in the muscles of the torso, upper legs, and upper arms. […] Symptoms can begin prior to six months of age, in childhood and, more rarely, in adulthood. […] In the most common form of the disease, lifespan is often less than two years of age. […] SMA is inherited in an autosomal recessive manner. […] In most cases, both parents must be carriers of the condition in order to have a child with SMA. […] Carriers are not themselves affected by the disease, but have a chance of having a child with the disease. […] If one parent is found to be a carrier, screening is recommended for their partner.

• #2 Spinal muscular atrophy – Wikipedia

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

  Those at risk of being carriers of SMN1 deletion, and thus at risk of having offspring affected by SMA, can undergo carrier analysis using a blood or saliva sample. The American College of Obstetricians and Gynecologists recommends all people thinking of becoming pregnant be tested to see if they are a carrier.

• #2 Spinal Muscular Atrophy | Baby’s First Test | Newborn Screening | Baby Health

  https://www.babysfirsttest.org/newborn-screening/conditions/spinal-muscular-atrophy

  Studies suggest that therapy for SMA is most effective when started in the first few months of life before significant loss of motor neurons occurs. This is why newborn screening for SMA is so important. […] SMA is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene, one from each parent, in order to have the condition. […] A genetic counselor or geneticist can help you understand the causes of the condition, discuss genetic testing for SMA, and understand what this diagnosis means for other family members and future pregnancies.

• #2 Spinal muscular atrophy: MedlinePlus Medical EncyclopediaLock

  https://medlineplus.gov/ency/article/000996.htm

  Spinal muscular atrophy (SMA) is a group of disorders of the motor neurons (motor cells). These disorders are passed down through families (inherited) and can appear at any stage of life. The disorder leads to muscle weakness and atrophy. […] SMA is a collection of different motor nerve (or neuron) diseases. The disease is caused by a lack of a protein (SMN) due to defective genes. […] Tests that may be ordered include: DNA testing to confirm diagnosis. […] There is no treatment to cure SMA. However, there are now three drugs approved by the FDA that slow how fast the muscle weakness progresses: Onasemnogene abeparvovec-xioi (Zolgensma), Risdiplam (Evrysdi), Nusinersen (Spinraza). […] Genetic counseling is recommended for people with a family history of SMA who want to have children.

• #2 SMA Diagnosis and Genetic Testing | SMA Disease Tests

  https://www.togetherinsma.com/en_us/home/introduction-to-sma/diagnosis.html

  Arriving at an SMA diagnosis may take some medical detective work. […] Because the signs and symptoms of SMA occur at different ages and with different severity, an initial diagnosis can be delayed. […] Healthcare providers may use other diagnostic tests, including additional genetic testing, electromyography, or a blood test to measure the level of creatine kinase an enzyme that leaks out of deteriorating muscles. […] Unlike a genetic molecular blood test, these tests may not accurately confirm a spinal muscular atrophy diagnosis. […] However, they may be used to rule out other forms of muscle disease. […] Although newborn screening is not yet standard practice, time to an SMA diagnosis is critical.

• #2 Spinal Muscular Atrophy (SMA) | PM&R KnowledgeNow

  https://now.aapmr.org/spinal-muscular-atrophy-sma/

  Spinal muscular atrophy (SMA) refers to a diverse group of genetic disorders characterized by degeneration of anterior horn cells of the spinal cord and brainstem motor nuclei with resultant muscle atrophy and progressive weakness. […] In the past electromyography/nerve conduction studies (EMG/NCS) and muscle biopsy were used to identify features of denervation and were the mainstay of diagnostic workup. However molecular genetic testing has now become the standard tool for diagnosis of SMA. It should be considered early in any infant with weakness or hypotonia or patients with symptoms of proximal predominant weakness, reduced or absent reflexes, tongue fasciculations and/or limb tremor (polyminimyoclonus). […] Genetic testing specifically for homozygous deletion will confirm the disease in 95% of patients. […] The homozygous deletion of SMN1 is essentially 100% specific for the diagnosis of SMA. Prenatal screening by chorionic villus sampling or amniocentesis is available and can potentially be used to catch the diagnosis early in a hypotonic infant in-vitro.

• #2 Spinal Muscular Atrophy Copy Number Analysis | Test Fact Sheet

  https://arupconsult.com/ati/spinal-muscular-atrophy

  Order to confirm a suspected diagnosis of SMA or for carrier screening. […] Order for prenatal diagnosis of SMA when both parents carry a known deletion of SMN1 or have a previous child with SMA caused by two SMN1 deletions. […] Diagnosis is based on clinical findings and molecular genetic testing. Electromyography (EMG), nerve conduction velocities (NCV), and muscle/nerve histology may aid in diagnosis. […] 95-98% of individuals with SMA have a homozygous loss of SMN1 (zero copies of SMN1). […] 2-5% of individuals with SMA have loss of SMN1 on one chromosome and a pathogenic sequence variant in the remaining copy of SMN1 (not detected by this test). […] A higher SMN2 copy number may correlate with milder disease severity in affected individuals. […] The presence of two or more copies of SMN1 usually indicates patient is not a carrier, although residual carrier risk exists.

• #2 Spinal Muscular Atrophy | Biogen

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

  When he was diagnosed with SMA at a young age, there was uncertainty about his future and what he would be able to accomplish. […] 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. […] Biogen has an innovative therapeutic pipeline that aims to address key unmet medical needs and make a meaningful daily impact for people affected by SMA. […] Biogens SMA development program encompasses 10 clinical studies, which have included more than 460 individuals across a broad spectrum of patient populations. […] Around 1 in every 4050 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.

• #3 Spinal Muscle Atrophy Workup: Laboratory Studies, Imaging Studies, Other Tests

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

  A simple blood test can confirm whether the child has a mutation that causes spinal muscle atrophy (SMA; also known as spinal muscular atrophy). The SMN1 deletion test is recommended as the first diagnostic step for a patient suspected of having SMA. The deletion status can be tested by using polymerase chain reaction (PCR) to determine if both copies of SMN1 exon 7 are absent, a finding that is noted in 95% of affected individuals. […] If the survival motor neuron (SMN) gene test is positive, the diagnosis is confirmed. However, 5% of children with the symptoms of SMA can have a negative SMN gene test and may require additional diagnostic testing. These tests can include electromyography (EMG), a nerve conduction study (NCS), or muscle biopsy and additional blood tests to help rule out other forms of muscle disease.

• #3 Spinal Muscular Atrophy (SMA) | PM&R KnowledgeNow

  https://now.aapmr.org/spinal-muscular-atrophy-sma/

  Spinal muscular atrophy (SMA) refers to a diverse group of genetic disorders characterized by degeneration of anterior horn cells of the spinal cord and brainstem motor nuclei with resultant muscle atrophy and progressive weakness. […] In the past electromyography/nerve conduction studies (EMG/NCS) and muscle biopsy were used to identify features of denervation and were the mainstay of diagnostic workup. However molecular genetic testing has now become the standard tool for diagnosis of SMA. It should be considered early in any infant with weakness or hypotonia or patients with symptoms of proximal predominant weakness, reduced or absent reflexes, tongue fasciculations and/or limb tremor (polyminimyoclonus). […] Genetic testing specifically for homozygous deletion will confirm the disease in 95% of patients. […] The homozygous deletion of SMN1 is essentially 100% specific for the diagnosis of SMA. Prenatal screening by chorionic villus sampling or amniocentesis is available and can potentially be used to catch the diagnosis early in a hypotonic infant in-vitro.

• #3 Spinal Muscular Atrophy

  https://patienteducation.asgct.org/disease-treatments/sma

  Early diagnosis can be completed through standard newborn screenings. […] It is highly important for this disease to be diagnosed as early as possible. […] Genetic testing can also be done soon after birth. […] It is best to speak with your healthcare provider or neurologist to understand and maneuver this difficult decision-making process. […] While pursuing existing or future SMA gene therapy treatments, it is important to note that gene therapy is not a cure and instead helps to control the progression of the disease.

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