Spinal Muscular Atrophy (SMA)

Disease/Disorder

Definition

Spinal muscular atrophy (SMA) refers to a diverse group of genetic disorders characterized by degeneration of anterior horn cells (lower motor neurons) of the spinal cord and brainstem motor nuclei with resultant muscle atrophy and progressive weakness.¹

Etiology

SMA is categorized by its mode of inheritance and the pattern of weakness that phenotypically manifests (i.e. proximal vs. distal weakness). The most common type of SMA is autosomal recessive proximal SMA, often referred to simply as proximal SMA which accounts for 95% of cases. This form results from a homozygous deletion or mutation of the survival motor neuron 1 gene (SMN1) on chromosome 5q-13.² It represents the most common genetic cause of death in infants.³

Epidemiology including risk factors and primary prevention

Spinal muscular atrophy disorders affect 1/6000 to 1/10,000 infants, with a pan-ethnic carrier frequency in the general population of 1/40-1/60 (ranging from 1/47 in the Caucasian population to 1/72 in the African American population). SMA type 1 (SMA-1) is the most common type (~60% of all patients with SMA), followed by SMA types 2 and 3. SMA types 0 and 4 are the most rare, with SMA type 4 being less than 1% of diagnosed cases.^5-8

Patho-anatomy/physiology

The SMN1 gene produces SMN protein which may influence mRNA synthesis in motor neurons (Friesen. Kerr, Up). A deficiency of this protein leads to improper function of alpha motor neurons in the spinal cord, leading to degeneration and severe muscle weakness (Ciafaloni) Humans have 2 forms of the SMN gene, SMN1 and SMN2. SMN1 produces primarily full length SMN protein but the SMN2 form (often called the SMA “back up gene”) is able to encode a small amount of normal SMN protein (10%-15%).⁴ All patients with SMA lack a working SMN1 gene, and the amount of full-length protein produced by SMN2 is insufficient for normal motor neuron function. SMN2 copy number varies in the population, and the variability of SMA disease severity is primarily related to a patient’s SMN2 copy number. Individuals with more SMN2 copies have a less severe form of SMA than those with fewer copies. However, other factors besides SMN2 copy number affect the phenotype such that prognosis cannot be fully predicted by the SMN2 copy number.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Various classification schemes exist for SMA. The International SMA Consortium scale published in 1991 is still commonly used and includes types 1, 2 and 3, based on age of onset and highest level of motor function achieved.⁹ Subsequent modifications have separated type 3 SMA into two subtypes based on age of onset and added groups 0 and 4. Early onset refers to Type I, late onset refers to Type II and III and adult onset is Type IV.

Table 1. Characteristics of SMA by Disease Type

Specific secondary or associated conditions and complications

Secondary conditions related to SMA include

• Restrictive lung disease (RLD) is most severe in SMA 0 resulting in death shortly after birth, followed by SMA 1, resulting in death within 2 years without ventilator support. In SMA 2 restrictive lung disease may be mild, but sleep-disordered breathing conditions can result in increased pulmonary infections with increased morbidity. RLD is less problematic in individuals with SMA types 3 and 4.
• Scoliosis occurs almost universally in SMA 2 but is rare in SMA 1.
• Contractures may be congenital (clubfeet) or may occur over time in association with progressive weakness.
• Constipation is common in SMA and may be due to poor abdominal muscle tone and immobility from weakness.
• Dysphagia is most common in SMA 1 and is due to bulbar weakness.

Essentials of Assessment

History

A complete family history should be obtained since SMA is inherited, however since 95% of cases have an autosomal recessive pattern (deletion or mutation of the SMN1 gene on chromosome 5q-13), parents can be silent carriers. These patients present with proximal weakness, with the condition referred to as proximal SMA.⁸

• SMA-0 has prenatal onset (previously classified as type 1), and presents as reduced fetal movements in utero. Severe weakness and hypotonia is noted at birth, often accompanied by heart defects, pulmonary hypoplasia, and arthrogryposis. Infants usually die by age 6 months. Genetic testing reveals one copy of the SMN2 gene.
• SMA-1 presents between 0-6 months age. Severe weakness and hypotonia are present with patients never able to sit independently, but with normal eye movement and expression due to sparing of upper cranial nerves. Weakness of lower cranial nerve muscles presents as a weak cry, with poor feeding and secretion management, with risk for aspiration. Weakness of intercostal muscles is greater than diaphragmatic, presenting as paradoxical breathing and progressive respiratory failure, with lifespan usually less than two years without ventilator support and other treatments. Cardiac muscle is spared. Genetic testing reveals two to three copies of the SMN2 gene.
• SMA-2 usually presents between 6-18 months age, with progressive proximal weakness, with legs more affected than arms. Patients can independently sit in childhood but will typically need assistance to sit by the second decade. Patients are never able to independently stand or walk. Respiratory muscle weakness is noted, and restrictive lung disease can also develop secondary to neuromuscular scoliosis. Lifespan is variable, but usually greater than 25 years. Genetic testing reveals three copies of the SMN2 gene.
• SMA-3 usually presents between 18 months and adulthood. There is often gait difficulty and proximal weakness with legs more affected than arms, but independent ambulation which can be lost over time, necessitating long term wheelchair use. Lifespan is normal, and typically without scoliosis or significant respiratory compromise. Genetic testing reveals three or four copies of the SMN2 gene.
• SMA-4 is rare, with mild weakness occurring in adulthood, independent ambulation, and a normal lifespan. Genetic testing reveals four to eight copies of the SMN2 gene.⁸

Other SMA types are rarer, and associated with genes other than the SMN1 gene, and may be caused by mutations on different chromosomes. These may differ in clinical presentation and inheritance pattern.

• SMA with respiratory distress (SMARD) – presentation is in infancy. Distal muscles and anterior horn cells of the upper spinal cord are more involved, thus influencing respiratory muscles including paralysis of the diaphragm. Inheritance pattern is autosomal recessive, involving mutations in the immunoglobulin mu binding protein (IGHMBP2) gene on chromosome 11.
• X-linked SMA – presentation in infancy with similar course as SMA-0 and SMA-1, but with X-linked inheritance pattern
• Other non-5q SMA which present in childhood or adulthood include a multitude of rare disorders with a variety of genetic and clinical presentations. Some prominent categories include distal SMA types, lower limb predominant types such as SMA-LED (spinal muscular atrophy with lower extremity predominant and dominant inheritance), and SBMA (spinal and bulbar muscular atrophy), also known as Kennedy’s Disease.

Physical examination

Table 2. Physical Exam

Functional assessment

Table 3.

Laboratory studies

Diagnostic Testing

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.¹⁰ 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 or mutation of the survival motor neuron 1 gene (SMN1) on chromosome 5q-13 will confirm the disease in 95% of patients.
• If negative, genetic testing for compound heterozygote deletion or mutation of the SMN1 gene should be undertaken. Similar to homozygous, clinical presentation of compound heterozygous would depend on the SMN2 gene copy numbers.
• A multitude of other genes presenting on different chromosomes have also been identified as presenting with SMA syndromes, including on chromosome 11, X-linked, and other non-5q SMA disorders.
• If genetic testing is still negative, one can consider electrodiagnostic testing, creatine kinase, and imaging to assist with diagnosis.

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. Prenatal screening of maternal blood can be used to check carrier status⁵.

Imaging

Imaging studies are not helpful in the diagnosis of SMA disorders but may be ordered as part of a workup for a hypotonic infant to exclude a central disorder.

Supplemental assessment tools

Electrodiagnostic (EDX) Testing

• Previously used when molecular testing was not widely available.
• Should be reserved only for evaluation of atypical patients and negative molecular work up (negative SMN1 deletion and SMN1mutation testing). EDX remains important for diagnostic workup in atypical cases and non-chromosome-5q-related SMA to demonstrate the neurogenic etiology of the illness.
• EDX studies show variable features of motor neuron involvement.
• On Electromyography (EMG), abnormal spontaneous activity (i.e. fibrillation potentials and positive sharp waves) is typically present. Delayed recruitment patterns with large motor unit action potentials (MUAPs) can be evident as well. In later stages, MUAPs may lack clear neurogenic features of long duration and large amplitude and instead have reduced amplitude and durations.
• Nerve Conduction Studies (NCS) show chronic motor axonal loss with perseveration of sensory nerve action potentials (SNAPs).
• Conduction velocities tend to be preserved with possible slight decrease due to axonal loss.

Early predictions of outcomes

• Outcome depends on what type of SMA the patient has; that is on severity of weakness, age at onset and on the highest functional level achieved.
• Disease severity amongst groups of patients correlates by SMN2 copy number, however due to idiosyncratic factors of each individual it cannot predict an individual’s potential severity and prognosis.^11-13 Also, knowledge of the SMN 2 copy number is important for therapeutic approaches and is currently used as a criterion for enrollment into clinical trials.¹⁴
• Compound muscle action potential (CMAP) amplitude on NCS correlates with clinical severity, age and function and has potential to be used for prognostication.^15-17
• Serum creatinine kinase (CK) and serum creatinine may play a role in predictive and pharmacodynamic biomarkers for SMA. CK levels are increased in SMA-3, and ambulatory patients with SMA, likely due to greater use of muscles and greater muscle reserve. Some studies show CK levels dropped in responders to nusinersen compared to non-responders in adults with SMA. Serum creatinine is also a marker of muscle mass and inversely correlates with disease severity, with higher levels present in SMA-3 and lowest in SMA-1. Creatinine levels reduced over a period of three months in the first year of life for infants with more severe forms of SMA (3 copies of SMN2), and thus can be a measure of disease progression.¹⁸
• Neurofilament proteins are released from neurons when injured and levels may be detected in blood and CSF. These are a biomarker for disease progression, prognostic and pharmacodynamic particularly in infants with SMA. In some studies, a higher baseline of plasma NF-H (heavy chain) correlated with earlier age of diagnosis and symptom onset and a lower baseline motor function. Also, it may indicate early biochemical effects of nusinersen treatment.¹⁸

Environmental

• Individuals with SMA-1 or SMA-2 will require an environment that is wheelchair accessible.
• It is recommended that individuals with SMA-1 and SMA-2 have a back-up electric generator in the event of a power outage, to allow functioning of respiratory support equipment.

Social role and social support system

• In a child with a diagnosis of SMA, it is important to provide anticipatory guidance to the patient’s family concerning the child’s ongoing medical and care needs.
• Counseling about the expectations of functional needs, and about the disease process itself, is essential to the family’s decision-making regarding care options and management of respiratory complications of SMA.
• Cure SMA is a non-profit organization which provides support to families, promotes and supports research with the goal of eradicating SMA⁸.

Professional issues

Ethical issues arise regarding emerging therapies used for treatment of SMA, including allowing parents and guardians to refuse FDA-approved medications. High costs of the medications also bring about concern for accessibility of treatments and equitable care.³⁷

Rehabilitation Management and Treatments

Available or current treatment guidelines

The clinical management of SMA depends upon the severity of weakness and the degree of respiratory involvement. In the last several years due to advancement in the understanding of SMA genetics and molecular mechanisms, genetic therapies have become a reality and have changed the therapeutic landscape, including survival and natural history of the disease.¹⁹ However, supportive care still continues to be a mainstream mode of management for SMA.¹⁰

Disease-Modifying Treatments

• There are three FDA approved medications for SMA: nusinersen (Spinraza®), risdiplam (Evrysdi®), and onasemnogene abeparvovec (Zolgensma®). These treatments aim to increase production of functional SMN protein in lower motor neurons. Early administration in the course of the disease yields better outcomes (age <2yrs), and especially for those who are not ventilator dependent.
• For children <2 years age, any of the three FDA approved medications may be utilized
• For adults or children >2 yrs age, nusinersen or risdiplam are recommended, though better results were noted for nusinersen in children <2 years age
• The general consensus in terms of timing is that treatment should be initiated as early as possible to yield the best potential for results due to the degenerative nature of this disease.
• Treatment is generally recommended for patients with moderate disease. For those with severe disease (ventilator dependence, enteric feeding, scoliosis), benefit to disease modifying treatments is less certain. For those with milder disease, functional yield is comparatively lower and the potential benefit gained may not be worth the risk of side effects. Patients therefore must be evaluated on a case-by-case basis.
• Nusinersen (Spinraza®) was FDA approved in 2016. Treatment has shown alteration of the natural history of the disease including improvement in motor function and quality of life. The ENDEAR trial enrolled infants age 7 months or older not requiring mechanical ventilation. The CHERISH trial enrolled children age 2-12 years with SMA2. The SMArtCARE registry noted better improvement in children who were <2 years old at the start of treatment.
  • Recommended age group: adults or children (any age)
  • Administration is intrathecal (does not cross the blood-brain barrier) with four initial loading doses given across eight weeks, and then maintenance doses every four months.
  • Potential risks are thrombocytopenia, coagulation abnormalities and renal toxicity. Platelet count, coagulation labs, and spot urine protein should be obtained at baseline and prior to each dose. Most common adverse effects are lower respiratory tract infection, constipation, fever, headache, vomiting, back pain and post lumbar puncture syndrome.⁴⁰
  • Mechanism of action: Gene modification (modifies the SMN2 gene product). Nusinersen is an antisense oligonucleotide (ASO). ASOs are synthetic nucleic acid molecules which alter SMN2 gene processing, increasing production of functional SMN protein.²⁷
• Onasemnogene abeparvovec (Zolgensma®), previously known as AVXS-101, was approved by the FDA in May 2019. Clinical trials were performed in SMA type 1 infants with biallelic mutations of the SMN1 gene and one or two SMN2 gene copies. Treatment reduced pulmonary and nutritional support requirements, improved motor function, and decreased hospitalization rate.It was studied in pre-symptomatic patients with SMA type 1. Patients showed achievement of age-appropriate motor milestones up to 14 months. STR1VE-US and STRIVE-EU trials enrolled infantile onset SMA with mean age 3.7 months who did not require noninvasive ventilation. After 12 months, many did not require permanent ventilation. This treatment may be ineffective in patients with antibodies to AAV9.
  • Recommended age group: children <2 yrs old
  • Administration is a one-time intravenous infusion
  • Potential risks are liver toxicity with cases of acute liver failure and fatality, thrombocytopenia, and elevated troponin-I. Liver function tests should be checked at baseline and for at least three months post infusion. Systemic corticosteroid should be administered before and after treatment to prevent liver inflammation. The most common adverse effects are elevated transaminases and vomiting.⁴¹
  • Mechanism of action: Gene therapy. It uses a viral vector, adeno-associated virus (AAVP-9) to deliver a functional copy of the SMN1 gene, replacing the defective gene in the patient’s cells.^{27, 28, 29,}
• Risdiplam (Evrysdi®) was approved by the FDA in 2020 for patients with SMA who are 2 months old or older. Clinical trials included the FIREFISH trial which enrolled infants with SMA1 who were 1-7 months and followed for 12 months. The FIREFISH part 2 trial used a higher dose of medication and followed the patients up to 24 months after treatment. Patients with treatment had a better survival rate without permanent ventilation than in the natural course of SMA, and better motor milestones including ability to sit unsupported for longer period. Risdiplam was studied in presymptomatic SMA (genetically diagnosed with two or more copies of SMN2) in the RAINBOWFISH trial. Motor outcomes were better than in the natural course of the disease, suggesting benefit from early treatment before symptom development. SMA 2 and nonambulatory SMA3 patients aged 2-25 years were enrolled in the SUNFISH trial and showed better motor function scores in the treatment group.⁴³
  • Recommended age group: adults or children (any age)
  • Administration is daily, given orally via a syringe
  • Potential risks are harm to fetal development in patients who are pregnant, and adverse effects on fertility in male patients. These conclusions were based on animal studies. Most common adverse effects are fever, diarrhea, and rash. In infantile-onset SMA, adverse effects also include constipation, vomiting and respiratory infections.⁴²
  • Mechanism of action: Gene modification (modifies the SMN2 gene product). Risdiplam is part of a category of medications called small molecules. It modifies pre-mRNA splicing from the SMN2 gene, thus increasing production of SMN protein. ^{27, 33}
• Combination treatments
  • Add on therapy – a second disease modifying agent can be added after incomplete or unsatisfactory response to the first agent. The JEWELFISH trial assessed Evrysdi® after treatment with another agent. Safety profile was similar to treatment in naïve patients. Motor scores showed stabilization. The RESPOND trial studied Spinraza® after Zolgensma® and initial results show improved motor function scores and reduced neurofilament light chain levels (biomarker for neurodegeneration).⁴⁴
  • Bridge therapy –patients can be treated with nusinersen or risidplam to stabilize them while waiting for eligibility for gene therapy (onasemnogene abeparvovec). Infants with increased AAV9 antibody titers can’t be treated with gene therapy until titers fall, since the treatment could be ineffective.
  • Switch therapy – this involves discontinuing long term nusinersen or risidiplam treatment and starting a different agent if a patient is not responding adequately, or experiencing side effects.³²

Pulmonary Management

• Restrictive lung disease is the most common cause of mortality for children with SMA. All children with SMA 1 and about 1/3^rd of those with SMA-2 will develop respiratory insufficiency or failure during childhood. Therefore, establishment with a pulmonary specialist is important early on during the time of initial diagnosis. Management options include noninvasive ventilatory support (such as noninvasive nasal ventilation) as well as invasive support with tracheostomy and a ventilator.
• Immunization against influenza, pneumococcus and respiratory syncytial virus is recommended as a preventative strategy.
• Parents should be educated about various care options and the role of invasive ventilation as well as related complications. They should also be educated about use of cough-assist devices, oral secretion management, chest physiotherapy and postural drainage.

Gastro-intestinal (GI) & Nutrition Management

• Dysphagia due to bulbar dysfunction can occur. Possible options for management include modification of diet consistencies to compensate for poor swallowing and protect against aspiration.
• For malnutrition due to poor oral intake, potential use of a gastrostomy tube can be considered.
• Constipation is a common complication due to immobility and can be managed by placement on a bowel program and encouraging mobility. Additional GI concerns include reflux and delayed gastric emptying and vomiting.¹⁴

Musculoskeletal Management

• In non-ambulatory patients, contracture prevention and management is important. This can be treated with regular stretching, bracing, serial casting, physical and occupational therapy. Adaptive equipment for mobility and ADL needs may include medical strollers, manual or power wheelchairs and any other related home medical equipment.
• Non-ambulatory patients will benefit from referral to a physical and occupational therapist for evaluation of adaptive equipment for mobility and ADLs, which may include an adaptive stroller, manual wheelchair or bath equipment. Some young children may use a supine standing frame if they have adequate trunk control, although tolerating this frame is difficult for older children who have developed lower extremity contractures.
• Physical exercise and therapy can optimize both endurance and strength. Patients should be encouraged to continue being as physically active as possible and encouraged to be involved in aqua-therapy and adaptive sports.
• Scoliosis, a likely complication in non-ambulatory patients, should be monitored regularly and treated as indicated with bracing for early stages or spinal fusion surgery for more severe cases. Scoliosis occurs in patients with SMA-2 and can contribute to restrictive lung disease in these patients. Spinal fusion surgery is the most effective and definitive treatment option.
• Hip instability including subluxation and dislocation is also common in SMA. Patients should be evaluated and managed according to pain level and ambulatory status.¹⁴
• Chronic pain is common in patients with SMA, with studies reporting approximately half of all adults and children with SMA reporting chronic pain (>3 months duration), with legs, back and hips as most common locations.^38,39

Accommodations

Communities and home set-ups that are wheelchair accessible are important for individuals with SMA 1 and SMA 2. Additionally, it is recommended that individuals with SMA 1 and SMA 2 have a back-up electric generator in the event of a power outage to allow functioning of respiratory support equipment.

Coordination of care

Multidisciplinary care is recommended. It is typically performed in a clinic setting with a neurologist, physiatrist, pulmonologist and orthopedist available. Patients benefit from early referral to physical and occupational therapists.

Patient & family education

Patient/family education and anticipatory guidance is critical due to the serious implications of a diagnosis of SMA. Counseling about the expected functional needs, goals and disease process itself is essential in order for the family to make decisions regarding care options.

Outcome measures

Physiologic measures such as motor unit number estimation, compound motor action potentials and MRI have been used. Functional outcome scales that have been used include the Alberta Infant Motor Scale, Wee Functional Independence Measure (WeeFIM), the Hammersmith scale and CHOP INTEND. These can be used to identify features requiring intervention and monitor progress in response to treatments. The Hammersmith scale was designed in 2003 for children with SMA type 2 and 3, with expanded versions for people with SMA 3 who are ambulatory.¹⁴

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Cognition is not affected in SMA, but children with SMA may be placed in inappropriate, cognitively unchallenging class settings due to the severity of their motor impairments. It is important to advocate for testing so that they are placed in the least restrictive setting to achieve optimal academic achievement.

Emerging/unique interventions

Combination of agents with different mechanisms of action, long term data is lacking.

Cutting Edge/Emerging and Unique Concepts and Practice

• Advances in our understanding of the genetics of SMA have led to an improved understanding of the pathophysiology of the various forms of SMA.
• The need for pre-symptomatic genetic testing is now a pressing issue in light of the development of effective therapies that are now in clinical use.
• Recent studies have shown dysfunction of the neuromuscular junction in SMA which may contribute to weakness and fatigability in these patients. Arnold WD, Severyn S, Zhao S, et al 2021 published adults with SMA had significant neuromuscular junction transmission defects that were not corrected with 14 months of nusinersen treatment.²⁶
• The effect of pyridostigmine (anti-cholinesterase) and impact on motor performance and fatigue in spinal muscular atrophy type 2-4 was recently published, indicating that the use of pyridostigmine may be beneficial as an additional therapy to current disease modifying agents.³⁴
• Oral reldesemtiv, a fast skeletal muscle troponin activator has been studied in patients with SMA types 2-4 for its effect on measures of skeletal muscle function or fatigability. Reldesemtiv is an investigational drug intended to slow the rate of calcium release from the regulatory troponin complex of fast skeletal muscle fibers. Results suggest that it is well tolerated and may be clinically beneficial.³⁵
• Myostatin is a protein that negatively regulates muscle growth. Anti-myostatin medications could increase muscle strength. There are clinical trials studying if the combination of risdiplam and anti-myostatin antibody in ambulatory children with SMA has the potential to improve motor function. ClinicalTrials.gov identifier: NCT05115110.³² An anti-myostatin monoclonal antibody known as Myostatin Inhibitor Apitegromab (SRK-015) is being investigated to improve motor function in SMA type 2 and 3. Phase 2 testing has shown improved motor function. Phase 3 trials are necessary.³⁶
• Future targets for SMA therapies include epigenetic regulation, including mechanisms to potentially increase expression of the SMN2 gene and functional SMN protein.³²

Gaps in the Evidence-Based Knowledge

• It’s not completely certain why low levels of SMN protein affect motor neuron functioning, however two possible reasons have been theorized. SMN aids in assembly of small nuclear ribonucleoproteins (snRNP’s) which are involved in pre-mRNA splicing. This may change splicing of particular genes that affect neuronal function. Another possibility is that SMN is necessary for transport of mRNA in neurons, and that this interference is what causes SMA.⁴⁵
• Larger studies are needed to establish the role of nusinersen and risdiplam in adults with SMA. However, limited studies show there is clinical meaningful improvement in adults with nusinersen.³⁰
• As the best outcomes have been observed the earlier the treatment is started, in utero therapy is an idea that’s been proposed. Finkel et. al presented a case report of a patient who was at risk for SMA 1 (amniocentesis confirmed absence of SMN1 and two copies of SMN2). Risdiplam was prescribed daily to the mother for approximately 6 weeks in her third trimester, and then to the infant on a daily basis after birth. The patient has had no phenotypical features of SMA including weakness or hypotonia, and has normal motor function.⁴⁶
• There isn’t current data comparing the different FDA approved disease modifying treatments to each other
• Combination treatments are being utilized in clinical practice, but current studies have been small with limited data, and without comparison to monotherapy.

References

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Original Version of the Topic

Suzanne Woodbury, MD. Spinal Muscular Atrophy (SMA). 11/14/2011

Previous Revision(s) of the Topic

William Arnold, MD, Monal Desai, MD. Spinal Muscular Atrophy (SMA). 11/28/2017.

Edwardo Ramos, MD, Laura M Serrano-Ortiz, MD. Spinal Muscular Atrophy (SMA). 6/16/2022

Author Disclosures

Sara Salim, MD
Nothing to Disclose