Spinal Muscular Atrophy
Overview
Other Names & Coding
5q SMA
Kugelberg-Welander disease
SMA
Werdnig-Hoffman disease
G12.0, Spinal muscular atrophy, type I; Werdnig-Hoffman
G12.1, Other inherited spinal muscular atrophy
G12.9, Spinal muscular atrophy, unspecified
ICD-10 for Spinal Muscular Atrophy and Related Syndromes (icd10data.com) provides coding details.
Prevalence
SMA is one of the most common recessively inherited disorders (second only to cystic fibrosis) and occurs in about 1:10,000 births. [Verhaart: 2017] Approximately 1:40 people are genetic carriers for type I SMA. [Verhaart: 2017] Until treatment became available, SMA type I was the leading inherited cause of infant mortality.Genetics
SMA is an autosomal recessive condition caused by homozygous deletion or mutation involving exon 7 of survival motor neuron 1 gene (SMN1) on chromosome 5q13. Although not well understood, the SMN protein complex appears to be involved in the biogenesis of specific ribonucleoproteins that control regulation of gene transcription. [Kolb: 2007] [Sumner: 2007]The severity of SMA is dependent on a second gene, SMN2, also on 5q13. SMN2 is the result of an ancestral duplication and is identical to SMN1 except for the presence of a missense mutation on exon 7 that disrupts a splicing enhancer but does not change the predicted protein sequence. This mutation results in mis-splicing of exon 7 and an inactive transcript; however, at a low rate, normal splicing occurs, providing a small amount of normal transcript and normal SMN protein. Severity of clinical symptoms is correlated with the number of copies of SMN2 since patients with more copies of SMN2 produce more normal SMN protein. While not perfectly correlated, most SMA type I patients have 1 or 2 SNM2 copies, and most patients with SMA type III have 3 or more copies. Treatments targeting up-regulation of expression of normal transcript from SMN2 have proven successful clinically, resulting in approval of nusinersen in 2016 and risdiplam in 2020.
With the addition of SMA to the recommended uniform screening panel, newborn screening programs for SMA are rapidly coming online in many states. Early initiation of treatment leads to far better outcomes, especially if treatment is started before the onset of symptoms and before significant loss of motor neurons becomes permanent. In most cases, newborn screening will identify homozygous deletion of SMN1 and will not identify carrier status or SMN2 copy number. Confirmatory testing, including SMN2 copy number after a positive newborn screen, is essential. [Baker: 2019] [Ke: 2019]. As newborn screening only detects infants with SMN1 deletions, about 95% of all cases of SMA but will miss those infants with one SMN1 deletion and one point mutation on the second copy.
Prognosis
In the last few years, 3 FDA-approved treatments have been approved for use for individuals with SMA - nusinersen (Spinraza), risdiplam (Evrysdi), and onasemnogene abeparvovec-xioi (Zolgensma). Each has pros and cons; none has long-term data, so the decision of which to use, or which combination of medications, can be difficult. Before these treatments became available, prognosis was variable and depended on the SMA subtype. Most children with type I SMA died before their second birthday. [Cobben: 2008] [Bach: 2007] [Finkel: 2014]Individuals with type II and type III SMA can have a normal life span but experience significant disability and respiratory or other complications. Anticipatory care that includes careful attention to respiratory, nutritional, and orthopedic issues can significantly prolong survival.
The availability of treatments, such as nusinersen, risdiplam, and onasemnogene abeparvovec-xioi (detailed in the Management section, below), has greatly changed the natural history and progression of SMA, especially when treatment is initiated early. [Ross: 2019] Although long-term data over a decade or more are not yet available, in many cases, infants who would not have lived past 2 years old are surviving longer and maintaining relatively good health. [De: 2019]
Practice Guidelines
Kirschner J, Butoianu N, Goemans N, Haberlova J, Kostera-Pruszczyk A, Mercuri E, van der Pol WL, Quijano-Roy S, Sejersen T,
Tizzano EF, Ziegler A, Servais L, Muntoni F.
European ad-hoc consensus statement on gene replacement therapy for spinal muscular atrophy.
Eur J Paediatr Neurol.
2020;28:38-43.
PubMed abstract / Full Text
Mercuri E, Finkel RS, Muntoni F, Wirth B, Montes J, Main M, Mazzone ES, Vitale M, Snyder B, Quijano-Roy S, Bertini E, Davis
RH, Meyer OH, Simonds AK, Schroth MK, Graham RJ, Kirschner J, Iannaccone ST, Crawford TO, Woods S, Qian Y, Sejersen T.
Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and
nutritional care.
Neuromuscul Disord.
2018;28(2):103-115.
PubMed abstract
Finkel RS, Mercuri E, Meyer OH, Simonds AK, Schroth MK, Graham RJ, Kirschner J, Iannaccone ST, Crawford TO, Woods S, Muntoni
F, Wirth B, Montes J, Main M, Mazzone ES, Vitale M, Snyder B, Quijano-Roy S, Bertini E, Davis RH, Qian Y, Sejersen T.
Diagnosis and management of spinal muscular atrophy: Part 2: Pulmonary and acute care; medications, supplements and immunizations;
other organ systems; and ethics.
Neuromuscul Disord.
2018;28(3):197-207.
PubMed abstract
Michelson D, Ciafaloni E, Ashwal S, Lewis E, Narayanaswami P, Oskoui M, Armstrong MJ.
Evidence in focus: Nusinersen use in spinal muscular atrophy: Report of the Guideline Development, Dissemination, and Implementation
Subcommittee of the American Academy of Neurology.
Neurology.
2018;91(20):923-933.
PubMed abstract
Roles of the Medical Home
Optimally, care of children with SMA should take place in a multi-disciplinary clinic. If one is not available, it is essential that the medical home helps families organize specialty care, remains watchful for changes in function, understands current treatment for acute illnesses, and advocates throughout the life of the child. Children with SMA will need surveillance of respiratory adequacy (awake and asleep), GI/nutritional balance, musculoskeletal status, dental hygiene, and individual and family functioning.
Clinical Assessment
Overview
Clinicians should suspect SMA in infants and children with proximal muscle weakness (shoulder and hip girdles) and absent or reduced deep tendon reflexes. In young infants, respiratory difficulties (e.g., bell-shaped chest or weak cough or cry) and feeding problems may be present from very early in the course. Patients with SMA are rapidly losing motor neurons at onset, and they risk permanent disability if treatment is not started as soon as possible.Pearls & Alerts for Assessment
Urgent referral when positive newborn screen for SMAA positive newborn screen for SMA should prompt urgent referral to a neuromuscular center where treatments can be coordinated quickly, before onset of symptoms. Outcomes for pre-symptomatic treatment are far superior to treatment at later stages. In one study of 25 infants with 2 or 3 copies of SMN2, treated pre-symptomatically with nusinersen, 22 of 25 reached independent ambulation. [De: 2019] For pre-symptomatic infants with SMA, symptoms can arise in the first weeks of life and time is critical. Delay of treatment even for a few days can result in permanent disability. [Butterfield: 2021]
Newborn screening will not pick up all cases of SMAIf SMA is suspected even in a child with negative newborn screening, further testing (SMN1 sequencing) is needed as newborn screening only identifies SMN1 deletion and 5% of patients are expected to have other mutations in the SMN1 gene. Children with one SMN1 deletion and a one point mutation on the second copy of SMN1 would have a negative screen.
Address possibility of respiratory failureInfants with type I SMA are susceptible to respiratory failure due to infection or aspiration. Addressing this possibility early with the family and implementing proactive measures (e.g., non-invasive ventilation, cough assist, and G-tube placement) can prevent emergency situations. Frequent pneumonias or respiratory illnesses may signal impending respiratory failure or aspiration.
Screening
For the Condition
In July of 2018, SMA was added to the list of recommended screening for newborns in the US by the Department of Health and Human Services. Implementation of newborn screening for SMA is progressing at variable rates, depending on the state-specific criteria. As of June 2021, 38 states participate in this screening, including 85% of births in the US. For further details, see Newborn Screening For SMA (Cure SMA). A positive newborn screen for SMA should prompt urgent referral to a neuromuscular center where treatments can be coordinated quickly before onset of symptoms. See Missing link with id: 5.xml.Of Family Members
Siblings of an individual with SMA have a 1:4 chance of being born with the condition and a 2:3 chance of being a carrier if not affected. Carrier testing is available for adults and siblings over age 18. [Carré: 2016] Although testing at-risk younger siblings who are asymptomatic for SMA is controversial, early identification of children with SMA may improve clinical outcome. The American College of Medical Genetics endorses offering SMN1 gene testing for early in pregnancy and all couples considering pregnancy. [Prior: 2008]Presentations
Presentations and clinical characteristics vary by SMA subtypes which are defined by maximal motor milestones attained. SMA type 1 individuals never reach independent sitting, type 2 individuals sit but never walk, and type 3 walk independently, even if only briefly. Early initiation of treatment has led to dramatic changes in natural history, challenging these traditional subtype distinctions. Regardless, treatment strategies remain based on current motor function as defined by groups of non-sitters, sitters, and walkers. Some families will choose not to treat/be unable to treat, and those children will present with the typical symptoms as noted below.- Type I SMA (Werdnig-Hoffman) presents in the first few weeks of life. Children never learn to sit or walk and have severe respiratory and swallowing problems, including difficulty handling oral secretions and a significantly shortened life span. Other features include poor head control, a bell-shaped chest, weak cry and cough, tongue atrophy and fasciculation, and paradoxical breathing.
- Type II SMA presents later in the first year of life or up to about 2 years of age. Children usually learn to sit but do not walk. Fine tremor-like movements in the hands and fingers may be noted from early in the course. As weakness progresses, children often have respiratory and swallowing problems, including difficulty gaining weight due to bulbar muscle weakness, weak cough, and nighttime hypoventilation. Swallowing problems and difficulties opening the jaw widely have been shown to contribute to malnutrition. [Messina: 2008] Joint contractures and scoliosis develop over time in nearly all affected children and warrant proactive intervention.
- Type III SMA (Kugelberg-Welander) is much more variable in onset than types I and II, but it usually presents in childhood or early adolescence. Children can sit and walk (although some may lose this ability over time). As with type II SMA, children with type III SMA may have fine tremor-like movements in the hands and fingers. Quadriceps atrophy may be pronounced. Children with type III SMA may have fewer problems with respiratory function and swallowing than children with type I or II SMA. Scoliosis, contractures, and joint pain are often noted in older children.
- Type 0 SMA presents before birth with decreased fetal movement noted around 30 weeks of gestation. Newborns are severely hypotonic at birth with congenital contractures, swallowing problems, and respiratory failure.
- Type IV SMA presents in adults and will not be discussed further here.
Diagnostic Criteria
Diagnosis is made by genetic testing for the common deletion of exon 7 of the SMN1 gene in children with appropriate clinical features. This testing is inexpensive and readily available; laboratories offering testing can be found at Testing for SMA (Genetic Testing Registry). Free testing programs are available, minimizing cost to patients and families. In states where newborn screening for SMA is available, diagnosis may come from the newborn screening program at just a few days of age, before clinical symptoms have emerged. A positive newborn screen should prompt urgent neuromuscular referral as symptoms can arise within the first weeks of life and treatment initiated before symptoms arise is the most effective.Identification of the copy number of the SMN2 gene assists in prognosis and is a standard feature of genetic testing for SMA. While most patients will have the common deletion of exon 7, about 5% of children who present with SMA have negative genetic testing due to presence of a deletion on 1 allele and a point mutation on the other. Clinical suspicion, more detailed gene testing, and electromyography (EMG) play important roles in diagnosis in these cases.
Clinical Classification
Classical clinical classifications are based on the maximal motor function achieved.- Children with type I SMA, which is the most common form, present before 6 months of age with generalized muscle weakness and progressive respiratory compromise. These children never achieve independent sitting.
- Children with type II SMA present between 6 months and 1 year of age with weakness and motor regression. Children with type II SMA sit independently but do not walk.
- Onset for type III SMA is variable from early childhood to adolescence. Children with type III SMA achieve independent ambulation, although they do not necessarily retain ambulation throughout life.
Differential Diagnosis
SMA is usually readily identified by clinical features and confirmed by genetic testing and, in many states, can now be identified by newborn screening. Differential diagnoses for a child with newly presenting progressive muscle weakness are described below.Infant botulism occurs in children up to 12 months of age. Symptoms start with constipation in a previously normal baby and are followed by decreased facial expression, poor swallowing, a weak cry, and decreased movement. Over time, the course is more acute than SMA. Diagnosis is made by recognition of clinical features and demonstration of botulinum toxin in the infant's stool. EMG can help to exclude other diagnoses.
Neuropathies are a wide spectrum of syndromes with various time courses. Sensory nerves are usually involved. Family history is often positive (e.g., Charcot-Marie-Tooth disease or hereditary motor sensory neuropathy). Acquired polyneuropathies, such as Guillain-Barre syndrome, have a rapid onset over a few days to a week. These are exceedingly rare in children under 2 years old. Diagnosis is confirmed by EMG and/or tests showing elevated cerebrospinal fluid (CSF) protein.
Metabolic myopathy (e.g., mitochondrial myopathy, Pompe disease) is much less common than SMA, but early features can be clinically similar. Infants with Pompe disease have severe progressive cardiac dysfunction not seen in SMA.
Duchenne muscular dystrophy occurs in boys only. In this condition, calves are large, creatine kinase (CK) is extremely high, and developmental delay is often present. It is diagnosed by genetic testing for mutations in the DMD gene.
X-linked SMA and SMA with respiratory distress (SMARD) may appear clinically similar to SMA, but they have different genetic etiologies and are therefore not currently amenable to treatment. SMARD1 presents as distal (not proximal) muscle weakness, with foot deformities as well as respiratory failure that often occurs suddenly. This condition is due to mutations in the IGHMBP2 gene on chromosome 11q13.3, which encodes the immunoglobulin micro-binding protein 2. [Kaindl: 2008] Infants with X-linked SMA may have a family history showing X-linked inheritance and will have negative SMN1 testing. An increasing number of new genes are being associated with these phenotypes and suspicion should prompt referral to a sub-specialty clinic for assessment.
Congenital myopathy presents with non-progressive weakness and is diagnosed by genetic testing and/or muscle biopsy.
History & Examination
Early recognition of weakness is critical to the initial evaluation. Assessment of weakness can be difficult in young children, but close attention to functional ability allows a good assessment of strength. Videos of children with and without weakness are available at the Child Muscle Weakness Organization and can be helpful in identifying subtle weakness.
Current & Past Medical History
Nutrition/GI: Has weight gain been adequate? Note that target weights for patients with muscle atrophy are lower than typical growing children. Ask about GI issues such as reflux, stomach pain, and constipation. Children with any neuromuscular disorder, including SMA, are osteopenic. Is Calcium and Vitamin D intake adequate? Any fractures? [Khatri: 2008] See Osteoporosis and Pathologic Fractures.Respiratory: Ask about breathing problems while awake, including while eating, for infants. Ask about history of pneumonia, strength of cough, reactive airway disease, recent pulmonary testing (oximetry), use of respiratory support (noninvasive respiratory support such as CPAP and BiPAP and nighttime or continuous ventilation), and use of a cough assist machine. Ask also about sleep, results of previous sleep studies, snoring as evidence of obstructive sleep apnea and hypoventilation, frequency of night waking, daytime sleepiness, and morning headaches. Check immunization history, including pneumococcal and flu vaccines.
Swallowing problems: Ask about coughing or choking while eating and drinking (especially thin fluids) and strength of cough. Ask if the family has a suction machine at home.
Musculoskeletal: Ask about any recent changes in muscle strength, fatigability, and functional abilities. Ask about fit and maintenance of the wheelchair, stander, or other equipment. Ask if the family has a license plate or placard for individuals with disabilities.
Orthopedic: Ask about orthotics use, joint pain, range of motion, and history of fractures.
HEENT: Ask about chronic ear infections.
Dental: Ask about dental history and the ability to open and close jaw.
Family History
SMA is an autosomal recessive disorder usually occurring with no family history; yet, providers should ask about infant and childhood deaths and consanguinity.Pregnancy/Perinatal History
Although there is no specific pregnancy history, sometimes mothers of children with type I SMA will report decreased fetal movement in late pregnancy. Children with type 0 and type I SMA may also have arthrogryposis at birth, difficulties with early feeding, and bell-shaped chests.Developmental & Educational Progress
Early motor milestones, such as the development of head control, will often be delayed. Babies may lie in the classic frog position when supine. Speech and language skills will not be delayed. Developmental testing will show profound delays in gross motor abilities, but cognitive abilities are spared. Measures of daily functioning, such as the Pediatric Evaluation of Disability Inventory (PEDI) (available for a fee), can help evaluate the child's functional abilities over time and are often available from the child's therapists. Ideally, these assessments should be part of the medical home record. Families should sign releases of information to obtain these records or bring copies of them to their appointments. A quick look at changes in the functional abilities of the child will help guide assessment of progression.Social & Family Functioning
Ask about family and community supports, access to resources, and any social issues for the child and family. Are necessary accommodations being made at school? Do the parents have anyone to stay with their child while they take a break? If the child with SMA is having difficulty with breathing, whether unaided or using BiPAP, how is that impacting the family, and what are their feelings concerning the next step? Is there a plan for an acute respiratory illness?Physical Exam
General
Babies with SMA are often alert and interactive, and children with SMA are often bright and quite social.Growth Parameters
Wt | Ht | BMI: Due to feeding problems, infants with SMA may be underweight or overweight (particularly when using a G-tube to augment feedings). Careful attention to feeding and growth patterns is important. With decreased muscle mass, a relatively low weight for length may be ideal. Standard growth charts for children may be inappropriate.Skin
Is there evidence of breakdown, cool extremities, mottling of skin, or yeast infection (tongue, body creases)?HEENT/Oral
Check ability to open jaw and the size of tonsils. Check for bad breath, dental caries, and drooling that may be caused by swallowing problems.Chest
The chest wall may appear bell-shaped. Listen to the lungs and observe for evidence of breathing difficulties. Check respiratory rate and look for paradoxical abdominal/chest wall movements. Observe cough or cry if possible. Consider spot oximetry, peak flow, and forced vital capacity measures. Measure chest circumference at the nipple line and follow growth. Chest and head circumference should be fairly equal in the first year. If the chest is not growing, the child is at a higher risk of respiratory compromise.Testing
Laboratory Testing
No routine testing is needed. Consider labs to evaluate for nutritional inadequacies, carnitine deficiency, hypercalcemia, and iron deficiency anemia. A urinalysis will detect urinary tract infection, etc. In the setting of illness, check for acidosis or electrolyte disturbances. Creatinine levels are normally low. Elevated CK levels are usually considered in those with muscle disorders such as Duchenne muscular dystrophy; however, CK levels can be elevated in patients with SMA undergoing active denervation.Imaging
Consider a video swallow study to look for aspiration or for children who take a long time to eat, have poor weight gain, or swallowing problems. Since the study is performed with a speech therapist present, strategies for safer feeding (e.g., thickening fluids) may be explored. A chest X-ray will help diagnose chronic aspiration or acute pneumonia; spine and hip X-rays will help diagnose scoliosis or hip dislocation.Genetic Testing
Genetic testing for SMA by detection of the common SMN1 deletion is readily available, and in many cases, can be obtained for free through various genetic testing programs. With urgency to treat quickly, many labs can provide results within a few days. Most children with SMA will have 2 copies of the common SMN1 deletion (1 from each parent). In some cases, the child has a single copy of the common SMN1 deletion and a second rare mutation on the other copy of SMN1. In this case, genetic testing requires sequencing of the SMN1 gene to identify missense, nonsense, or frameshift mutations. A small percentage of children with SMA will be negative for the common exon 7 deletion, but when more detailed testing is performed, the child may have a mutation on SMN1 not included in the routine genetic testing.Although the number of SMN2 copies is not needed to diagnose SMA, guidelines recommend that this be obtained to allow assessment of the predicted SMA phenotype. In most cases, those with type I SMA have 2 copies, type II SMA have 3 copies, and type III SMA have 4 copies of SMN2. In addition, eligibility for medication trials for SMA may depend on SMN2 copy number. [Mercuri: 2018] See Testing for SMA (Genetic Testing Registry).
Other Testing
Other possible testing:- Electromyography (EMG) can indicate probable SMA, in which case, genetic testing should follow.
- Pulmonary function tests and sleep studies are used to evaluate respiratory status as needed.
- Nutritional assessments are helpful for evaluation of children who are underweight or overweight.
- DEXA scans are performed if the child has a history of fractures or, as a baseline if the child has been immobile and confined to a wheelchair for an extended period, especially if the child is on valproic acid or proton pump inhibitors.
Specialty Collaborations & Other Services
When available, an SMA-specific clinic for children is preferred for evaluation and management. Depending on the location, additional involvement of sub-specialists, such as those in physical medicine & rehabilitation and pulmonology, can be helpful.
Neuromuscular Clinics (see MT providers [4])
Multidisciplinary care for children with SMA and other neuromuscular disorders is often available through clinics sponsored by the Muscular Dystrophy Association. In partnership with the primary care team, these clinics can coordinate anticipatory care, subspecialty referrals, and treatment with newly approved therapies.
Medical Genetics (see MT providers [8])
Genetics and genetic counseling may be available in an SMA-specific or neuromuscular clinic. If not, an initial visit for genetic testing and discussion of test results, and periodic visits to address new issues, may be helpful.
Pediatric Pulmonology (see MT providers [7])
Referral is particularly important for children with type 0 and type I SMA because of the risk for respiratory compromise. Nighttime ventilation is often affected first; deterioration may be subtle. Early pulmonology consultation is recommended, even for children with SMA that are doing well.
Pediatric Gastroenterology (see MT providers [15])
Nutrition support is available in most subspecialty clinics with expertise in SMA. Referral may be helpful for evaluation and management of eating and nutrition problems. Swallowing difficulty, reflux, constipation, or failure to gain weight appropriately should also prompt consideration of referral.
Pediatric Orthopedics (see MT providers [18])
Most children with SMA of any type will benefit from periodic referrals for evaluation and management of musculoskeletal complications. If the child with SMA has been born with arthrogryposis, early involvement is critical.
Pediatric Physical Medicine & Rehabilitation (see MT providers [6])
Referral can help optimize mobility and the activities of daily living, and it usually includes physical, occupational, and speech therapy.
Pediatric Otolaryngology (see MT providers [5])
Consider a referral if obstructive sleep apnea is a concern.
Treatment & Management
Pearls & Alerts for Treatment & Management
New specific treatments are available for SMA
Nusinersen (Spinraza) is now approved by the FDA for
individuals with all types of SMA. There is emerging data supporting
dramatic benefits even in severely affected patients, but long-term outcomes
are not known. Nusinersen has generally been well-tolerated. There is Class
III evidence that infants with homozygous mutations/deletions of
SMN1 have improved, ventilation-free survival at
age 24 months. Finally, there is evidence that in children aged 2-12
diagnosed after 6 months of age (SMA type II patients) nusinersen results in
greater improvement in motor function after 15 months of treatment.
Nusinersen is extremely expensive, and there are
many inequalities between children without insurance and children with
various types of insurance. It needs to be given by lumbar puncture and a
controlled environment and sedation are needed. Nusinersen is given by 4
loading doses (the first 3 at 14-day intervals and the 4th 30 days after the
third dose) and then 1 dose every 4 months indefinitely. Administration of
nusinersen may be particularly difficult in children who develop scoliosis
and in the setting of spine surgery. In addition to the price of nusinersen,
administration costs also need to be considered.
Onasemnogene abeparvovec-xioi
(Zolgensma) was approved by the FDA in2019 for children
under 2 years of age with SMA. Onasemnogene abeparvovec-xioi is administered
by IV as a one-time dose as soon as possible after diagnosis. To qualify
currently, children must be under 2 with bi-allelic mutations in the
survival motor neuron 1 (SMN1) gene and absent
antibody to the vector, AAV9. Children are treated with steroids one day
prior to dosing with Zolgensma and for about 60 days thereafter to mitigate
the chance for liver inflammation and other adverse effects. Liver function,
platelet count, and troponin-I are monitored after Zolgensma infusion. See
Zolgensma Package Insert (
210 KB). Current pricing
is >$2 million for this 1-time dose.
Risdiplam (Evrysdi) is an
oral medication given daily that works similarly to nusinersen. It was
approved by the FDA in August 2020 for children 2 months of age and older,
including adults with SMA. It should be avoided in pregnancy and may cause
problems with male fertility. Price is about $300,000 to $400,000 annually
and is given indefinitely. See EVRYSDI Prescribing Information ( 514 KB).
Which
treatment to pick is a complex question and should be discussed carefully
with the neuromuscular specialist. Data are evolving rapidly and treatment
should be tailored to the specific risks/benefits of the child. Outcome with
any of the 3 medications is better if given/started younger than 3 months of
age and with good baseline motor function. [Ramdas: 2020] Zolgensma is only available for children younger than
2, and those children must not have antibodies to the AAV9 vector. Both
risdiplam and nusinersen are approved for use in types 1, 2, and 3, although
risdiplam cannot be given to infants younger than 2 months of age.
Nusinersen must be given by lumbar puncture and risdiplam may cause birth
defects and male infertility. These factors and others must be weighed by
the family in consultation with the Neuromuscular specialist. Additionally,
families may wish to try a second medication based on outcome of the first
medication tried. [Ramdas: 2020]
Expectant management includes increased nutritional management and attention to respiratory status before and after surgery and during acute hospital visits. Temporary supplementation with nasogastric tubes or nasojejunal tubes, or peripheral or total parental nutrition, may be helpful.
Written care plans facilitate emergency careEmergency room visits for families of children with SMA are challenging because of the need for families to detail their histories and preferences, as well as the reason for their visit. Plans for what to do in case of respiratory failure should be made and revised at non-acute medical home visits. Provide families with documentation so their resuscitation desires can be shared with other clinicians.
Early postoperative ambulation helps maintain strengthRequired inactivity following major surgery (e.g., for scoliosis or hip dislocation) may precipitate the loss of ambulation. Early re-institution of ambulation in these settings can help significantly in maintaining strength.
How should common problems be managed differently in children with Spinal Muscular Atrophy?
Growth or Weight Gain
Standard growth charts often are not appropriate for children with SMA. Children who are following “normal” growth curves may be functionally obese and at risk for insulin resistance and complications of a metabolic syndrome. Muscle atrophy complicates management of nutritional issues; close monitoring is essential. Children with type I SMA have early dysphagia; early placement of G-tube with Nissen fundoplication is often necessary to prevent aspiration and pneumonia.Development (Cognitive, Motor, Language, Social-Emotional)
Cognitive and emotional development is normal in children with SMA. While language is normal from a neurologic perspective, communication, especially with type I SMA, can be difficult due to weakness. Children may need adaptive devices to assist communication.Viral Infections
Due to weakness of respiratory muscles and poor cough, children with SMA are at risk for significant upper respiratory infections. Families should be encouraged to take appropriate precautions (e.g., handwashing and limiting exposure to sick individuals). Patients should receive annual flu vaccine; RSV prophylaxis is appropriate in infants with type I SMA.Bacterial Infections
Children with SMA are at risk for bacterial pneumonia as a primary feature or as a complication of viral upper respiratory infection or aspiration. Age-appropriate pneumococcal vaccination is recommended. Early use of non-invasive ventilation and Cough Assist are appropriate preventive measures.Systems
Neurology
Specialty Collaborations & Other Services
Neuromuscular Clinics (see MT providers [4])
Multidisciplinary care for children with SMA and other neuromuscular disorders is recommended. In partnership with the primary care team, these clinics can coordinate treatment, anticipatory care, and subspecialty referrals.
Pediatric Neurology (see MT providers [15])
In areas without specialty clinics, pediatric neurologists with expertise in neuromuscular disorders should be involved in the management of children with SMA.
Respiratory
Consider a sleep study for identification of obstructive sleep apnea and central hypoventilation. These problems may occur before the child has obvious daytime problems. Nighttime BiPAP is usually necessary when the vital capacity is less than 40% of the predicted value. BiPAP can also be used in daytime during periods of increased need, such as with a respiratory illness or following surgery. The Medical Home Portal's CPAP & BIPAP Therapy for Children topic provides more information about indications for use and follow-up care.
Optimal preventive treatment includes nutritional optimization, especially with surgeries and illnesses. For some children, breath stacking methods and incentive spirometry can be taught, usually by staff at the pulmonology clinic. Breath stacking involves repetitions of taking a breath and holding it. Daily practice can be helpful for children who are losing lung capacity, but adherence is difficult.
If the child has a weak cough, percussion and postural drainage should be initiated; management of secretions is further improved by use of a cough-assist device. [Fauroux: 2008] Respiratory secretions should be managed with the help of an ENT if necessary. Consider medications to reduce secretions, botulinum toxin injections, and salivary gland ligation for children who cannot manage secretions. Swallowing problems should be managed optimally, for example, with thickened liquids and G-tube feeds; Nissen fundoplication may be helpful when reflux is present.
Ensure that immunizations, especially pneumococcal and yearly flu vaccines, are up to date. RSV prophylaxis should be given to non-sitters and most sitters. Respiratory infections and symptoms of reactive airway disease should be treated early and aggressively. If hospitalization is necessary for acute, severe respiratory illness, consider the use of non-invasive ventilation; children with SMA often have difficulty weaning from a ventilator. Supplemental oxygen without mechanical ventilation should be used with care as it may decrease respiratory drive, leading to hypercarbia and atelectasis.
Specialty Collaborations & Other Services
Pediatric Pulmonology (see MT providers [7])
Pulmonology should manage most children with SMA concurrently with the medical home. Children should be referred at diagnosis and periodically for management.
Pediatric Sleep Medicine (see MT providers [4])
Children with SMA may need breathing assistance during sleep before they demonstrate problems while awake; refer for sleep evaluations and management as needed.
Pediatric Otolaryngology (see MT providers [5])
Consider referral for drooling, swallowing problems, or sleep apnea.
Nutrition/Growth/Bone
Poor weight gain is common and often attributed to the decreased intake of food and the increased energy demands required for the work of breathing. Registered dieticians should be involved when infants are grossly underweight. Increasing calories may involve Power Packing, pureeing foods, or gastrostomy feeds (either exclusively or in addition to oral feeding). Although the decision to proceed with G-tube placement can be difficult, prolonged feeding time may make the logistics of caring for non-sitters with SMA very difficult. Families may prefer to start with a nasogastric tube before proceeding with G-tube placement. For an introduction to various kinds of feeding tubes and an overview of the role of the medical home in feeding tube care, see Feeding Tubes & Gastrostomies in Children.
Excessive weight gain can also occur in sitters and walkers and can make mobility even more difficult; preventing excessive weight gain is easier than losing weight. Nutrition experts should be involved when a trend toward becoming overweight is first noted.
Specialty Collaborations & Other Services
Nutrition Assessment Services (see MT providers [1])
Referral may be helpful in underweight and overweight children with SMA.
Pediatric Endocrinology (see MT providers [14])
Consider referral for children who have low bone mineral density on DEXA scans and history of fractures.
Musculoskeletal
Devices for upright positioning are prescribed for non-sitters to help with lung function, gastrointestinal function, and developmental goals. For sitters and non-sitters, standing equipment should be prescribed and used for a goal of 1 to 2 hours a day. This can help with lung and gastrointestinal function, decrease fracture risk, and delay scoliosis and contracture development. Orthotics and walking equipment should be provided, even if functional walking for all activities is not a practical goal. Prescribe scooters, wheelchairs (manual and/or powered), or other equipment, as necessary, for all children with SMA to allow participation in age-appropriate community activities. To avoid progression of contractures, implement daily range of motion exercises and early return to weight-bearing activities after surgeries.
Hip subluxation and dislocation are common problems for non-sitters, sitters, and, occasionally, walkers. Imaging of the hip should be performed bi-annually or annually. Hip dislocation can make sitting balance difficult, interfere with already compromised respiratory function, and lead to chronic pain. The risks and benefits of surgery for hip subluxation should be weighed by the family who is consulting with an experienced orthopedic surgeon. When surgery is being considered for walkers, be aware that the period of inactivity may lead to contractures or changes in functional walking patterns.
Specialty Collaborations & Other Services
Pediatric Orthopedics (see MT providers [18])
Refer early for evaluation and management of hip dislocation, scoliosis, and joint contractures; ideally, the sub-specialist will have experience treating children with SMA.
Hospitals (see MT providers [26])
Shriners Hospitals offer orthopedic care to children with SMA. For a map of locations, see Shriners Hospitals for Children.
Pediatric Physical Medicine & Rehabilitation (see MT providers [6])
Refer to optimize functional abilities, including activities of daily living and mobility.
Physical Therapy (see MT providers [46])
Consider early referral to assist with range of motion, strengthening, mobility equipment, and prevention of contractures.
Early Intervention for Children with Disabilities/Delays (see MT providers [27])
Young children are usually eligible for different types of therapies (physical, occupational, speech, etc.) through Early Intervention or programs administered at the local community level.
Nose/Throat/Mouth/Swallowing
Specialty Collaborations & Other Services
Pediatric Gastroenterology (see MT providers [15])
Referral may be helpful for children who are underweight, aspirating, or who are having difficulty swallowing. Placement of a G-tube may be beneficial.
General Pediatric Surgery (see MT providers [2])
Referral may be helpful for G-tube insertion, especially if a fundoplication is also being considered.
Gastro-Intestinal & Bowel Function
Specialty Collaborations & Other Services
Pediatric Gastroenterology (see MT providers [15])
Consider referral for children who do not respond to typical management.
General Pediatric Surgery (see MT providers [2])
Depending on local expertise, children requiring G-tube placement may be referred.
Developmental - Behavioral Pediatrics (see MT providers [8])
Depending on local expertise, behavioral and medical management of constipation may benefit from referral.
Dental
Specialty Collaborations & Other Services
Pediatric Dentistry (see MT providers [53])
Children with SMA should be referred early and visit at least every 6 months for ongoing care.
General Dentistry (see MT providers [257])
The dentists in this list have expressed interest and experience in treating children and youth with special health care needs.
Recreation & Leisure
Specialty Collaborations & Other Services
Adaptive Sports and Recreation (see MT providers [14])
Encourage families to seek out recreational outlets for their child.
Funding & Access to Care
Specialty Collaborations & Other Services
Neuromuscular Clinics (see MT providers [4])
Clinics that provide care for a variety of conditions, including muscular dystrophy and spinal muscular atrophy.
Family
Appropriate care for children with SMA encompasses many options, and open discussion of alternatives are very helpful for families. Some families will choose to forego diagnostic and therapeutic interventions that they feel are invasive, whereas others will choose to proceed aggressively with interventions that might prolong life. All caregivers need to understand the family’s preferences. Discussions are best accomplished over time and in non-acute settings, rather than in the midst of an emergency room visit for pneumonia requiring intubation, for example. Preventive management, such as early implementation of non-invasive ventilation, will help avoid crises. The decision to aggressively manage SMA is a dynamic one that can be reconsidered whenever appropriate. Offer pediatric hospice in situations where aggressive intervention is not chosen.
Specialty Collaborations & Other Services
Hospice & Palliative Care (see MT providers [6])
Hospice services that have expertise in the care of children should be involved when necessary.
Wish Foundations (see MT providers [18])
Refer, as appropriate, when children are between 2 1/2 and 18 years of age.
Medical Genetics (see MT providers [8])
Families can benefit from periodic visits to review issues and address new questions (e.g., progress in genetic studies, options for prenatal and preimplantation diagnosis to help with reproductive planning or risks for siblings of a child with SMA). In many cases, a genetic counselor with expertise in neuromuscular disorders is available through Neuromuscular Clinics and Muscular Dystrophy Association clinics.
Ask the Specialist
What are the earliest signs of SMA?
Signs and symptoms depend on a patient’s age and SMA subtype. Classically, children present with hypotonia, proximal weakness (shoulders and hips), feeding difficulties, and/or complications of respiratory insufficiency. Early signs of weakness include:
- Abdominal breathing or accessory muscle use
- A feeling of “slipping through hands” when held suspended by examiner under armpits
- Inability to voluntarily flex neck when supine or has head lag when pulled to sit
- In older children, difficulty rising from floor (including Gowers maneuver, full or modified)
What are the most pertinent issues to focus on during a routine well-child visit for a patient with SMA?
Ongoing and proactive assessment of sitting status, joint range of motion, feeding ability, weight, and respiratory status can enhance the quality of life and life span for children with SMA. Asking about family and community supports and access to resources that may affect the care of a child with SMA is also critical.
How does SMA affect growth and development?
Children with SMA are at risk for nutritional deficiencies and being underweight. Non-sitters, in particular, are commonly underweight secondary to decreased intake and the increased energy expenditure for the work of breathing. Standard weight charts are not applicable due to reduced muscle mass despite caloric supplementation. Children with SMA that are following the “normal” growth curves may be functionally obese and at risk for complications of metabolic syndrome.
Resources for Clinicians
On the Web
Clinical guidelines for SMA (Cure SMA)
A collection of clinical guidelines on various aspects of SMA compiled by CureSMA.
Respiratory Guidelines (Cure SMA) ( 32 KB)
Respiratory guidelines including ongoing management and equipment
Nutritional Care Guidelines (Cure SMA) ( 68 KB)
Proactive nutritional management tips for children with SMA.
Musculoskeletal issues in SMA (Cure SMA)
Compiled information about musculoskeletal issues including treatment and equipment that might be needed
Child Muscle Weakness Organization
Information and videos to help increase clinicians’ awareness of peripheral neuromuscular disease as a cause of developmental
delay in young children and the early symptoms of neuromuscular disorders; National Task Force for the Early Identification
of Childhood Neuromuscular Disorders.
Spinal Muscular Atrophy (GeneReviews)
An expert-authored, peer-reviewed, current disease description that applies genetic testing to diagnosis and management information;
U.S. National Library of Medicine.
Spinal Muscular Atrophy Type I (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance
in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine
Spinal Muscular Atrophy Type II (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance
in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine
Spinal Muscular Atrophy Type III (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance
in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine
Helpful Articles
PubMed search for spinal muscular atrophy in children, last 2 years.
Butterfield RJ.
Spinal Muscular Atrophy Treatments, Newborn Screening, and the Creation of a Neurogenetics Urgency.
Semin Pediatr Neurol.
2021;38:100899.
PubMed abstract / Full Text
Clinical Tools
Assessment Tools/Scales
Pediatric Evaluation of Disability Inventory (PEDI)
Helps evaluate functional disabilities of children ages 6 months to 7 years old; completion time of 45-60 minutes; manual
scoring; purchase required.
Patient Education & Instructions
Living with SMA (Cure SMA)
Excellent resource for families dealing with the day-to-day issues related to SMA. Contains information about standards of
care, school, home, equipment needs, and community resources.
Resources for Patients & Families
Information on the Web
SMA Foundation
The mission of the SMA Foundation is to accelerate treatment for children with SMA. Families will find detailed information
about SMA, up-to-date information about drugs in development, and support.
Spinal Muscular Atrophy (MedlinePlus)
A brief description of SMA, along with numerous links to further information; sponsored by the National Library of Medicine.
Genetic Conditions: Spinal Muscular Atrophy (MedlinePlus)
Excellent, detailed review of condition for patients and families; National Library of Medicine and National Institutes of
Health.
National & Local Support
Cure SMA
Offers information about research in SMA, access to support and local chapters, and opportunities for fundraising.
Children's Hospice International
An organization that supports the idea that critically ill children should have access to hospice/palliative care along with
curative care from the time their life-threatening illness has been diagnosed.
Never Give Up
Nonprofit organization that engages in leading scientists and policymakers to create treatments and a cure for SMA.
SMA Coalition
A coalition of SMA-focused nonprofits working toward increased awareness and help for those with SMA.
Studies/Registries
Spinal Muscular Atrophy (clinicaltrials.gov)
Studies looking at better understanding, diagnosing, and treating this condition; from the National Library of Medicine.
Services for Patients & Families in Montana (MT)
| Service Categories | # of providers* in: | MT | NW | Other states (5) (show) | | NM | NV | OH | RI | UT |
|---|---|---|---|---|---|---|---|---|---|---|
| Adaptive Sports and Recreation | 14 | 9 | 26 | 20 | 9 | 27 | 68 | |||
| Assistive Technology Equipment | 42 | 34 | 47 | 43 | 34 | 40 | 54 | |||
| Camps for Children with Special Needs | 36 | 20 | 23 | 25 | 20 | 52 | 39 | |||
| Developmental - Behavioral Pediatrics | 8 | 1 | 1 | 2 | 1 | 12 | 9 | |||
| Early Intervention for Children with Disabilities/Delays | 27 | 3 | 36 | 31 | 3 | 14 | 55 | |||
| General Dentistry | 257 | 1 | 7 | 16 | 1 | 34 | 136 | |||
| General Pediatric Surgery | 2 | 5 | 4 | 2 | ||||||
| Hospice & Palliative Care | 6 | 3 | 4 | 22 | 3 | 4 | 52 | |||
| Hospitals | 26 | 3 | 3 | 22 | 3 | 14 | 63 | |||
| Medical Genetics | 8 | 1 | 2 | 5 | 1 | 4 | 6 | |||
| Neuromuscular Clinics | 4 | 1 | 1 | 2 | 1 | 3 | 5 | |||
| Nutrition Assessment Services | 1 | 3 | 2 | 7 | ||||||
| Occupational Therapy | 44 | 1 | 23 | 27 | 1 | 18 | 38 | |||
| Pediatric Dentistry | 53 | 2 | 4 | 30 | 2 | 41 | 62 | |||
| Pediatric Endocrinology | 14 | 1 | 1 | 6 | 1 | 13 | 3 | |||
| Pediatric Gastroenterology | 15 | 1 | 1 | 6 | 1 | 19 | 4 | |||
| Pediatric Neurology | 15 | 5 | 17 | 5 | ||||||
| Pediatric Orthopedics | 18 | 4 | 4 | 8 | 4 | 16 | 20 | |||
| Pediatric Otolaryngology | 5 | 1 | 1 | 5 | 1 | 7 | 9 | |||
| Pediatric Physical Medicine & Rehabilitation | 6 | 3 | 3 | 3 | 3 | 6 | 15 | |||
| Pediatric Pulmonology | 7 | 4 | 8 | 4 | ||||||
| Pediatric Sleep Medicine | 4 | 2 | 3 | |||||||
| Physical Therapy | 46 | 17 | 11 | 5 | 50 | |||||
| Recreational Facilities | 16 | 3 | 10 | 87 | 3 | 21 | 83 | |||
| Social & Recreational Opportunities | 6 | 1 | 5 | 3 | 1 | 10 | 7 | |||
| Speech - Language Pathologists | 55 | 4 | 19 | 13 | 4 | 30 | 71 | |||
| Swallow Studies | 1 | 1 | ||||||||
| Wish Foundations | 18 | 15 | 15 | 17 | 15 | 18 | 21 | |||
For services not listed above, browse our Services categories or search our database.
* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.
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