Spinal Muscular Atrophy
Spinal Muscular Atrophy: Excerpt from The 5-Minute Pediatric Consult
Peter B. Kang, MD
Spinal Muscular Atrophy - BASICS
Spinal Muscular Atrophy - description
- Spinal muscular atrophy (SMA) is a progressive disorder of motor neurons in the spinal cord.
- Major symptom is weakness.
- Most common and severe form, type I, also known as Werdnig–Hoffman disease, begins before 6 months of age.
- Onset in type II is between 6 and 18 months of age.
- Onset in type III (Kugelberg–Welander disease) is after 18 months of age.
An apparently minor respiratory infection may carry a higher risk of respiratory failure in SMA I and later stages of SMA II and III. Depending on resuscitation status, consider admitting such a patient to the hospital for observation.
Spinal Muscular Atrophy - epidemiology
One of the most common inherited lethal diseases in humans
Spinal Muscular Atrophy - incidence
Incidence estimated at 1 in 6,000–24,000 live births; carrier frequency 1 in 40
Spinal Muscular Atrophy - risk factors
Spinal Muscular Atrophy - genetics
- Genetic testing should be performed in all cases, even when the diagnosis appears clear.
- Genetic counseling is critical for all families with children affected by SMA, as the chance of recurrence is 25%.
Spinal Muscular Atrophy - etiology
- The classic form (types I, II, and III) follows an autosomal recessive inheritance and is caused by mutations in the survival motor neuron (SMN) gene on 5q11.2 to 13.3.
- 2 copies of SMN on each chromosome. SMN1 (SMNt), the telomeric copy, produces stable SMN protein. Homozygous deletion of exon 7 in SMN1 is the most common cause of SMA type I. SMN2 (SMNc), the centromeric copy, produces an unstable, truncated protein product more abundantly than the stable, full-length protein product, but its presence ameliorates the severity of the condition. SMA types II and III often result from a conversion of SMN1 to SMN2.
- The SMN protein plays a role in RNA processing; it is unclear why motor neurons (anterior horn cells) are selectively vulnerable to this defect.
Spinal Muscular Atrophy - associated conditions
Other anterior horn cell diseases:
- SMA variants are associated with arthrogryposis, pontocerebellar hypoplasia, congenital fractures, and congenital heart disease. Few such cases have been shown to have SMN mutations.
- Fazio–Londe disease: Rare degeneration of anterior horn cells in the brain stem, childhood onset
- Kennedy disease: X-linked anterior horn cell disease with adult onset; affected men have gynecomastia, and reduced fertility
Spinal Muscular Atrophy - DIAGNOSIS
Spinal Muscular Atrophy - signs & symptoms
Spinal Muscular Atrophy - history
- Hypotonia and weakness are the primary features. Infants with SMA I will be floppy, less active, and have delayed motor milestones.
- Reduced vigor of prenatal movements
Spinal Muscular Atrophy - physical exam
- Weakness suggests a neuromuscular cause, whereas normal strength is more consistent with a central etiology. Absent or reduced reflexes also suggest a neuromuscular disorder. A proximal pattern of weakness is consistent with SMA, myopathies, and muscular dystrophies; a distal pattern suggests polyneuropathies.
- Weakness is almost universally symmetrical, but occasional cases of asymmetric weakness have been reported in SMA III.
- Extraocular movements and facial strength remain intact in SMA.
- Dysmorphic features, or involvement of other organs, may point to alternative diagnoses. Occasionally, SMA presents with contractures, (spectrum of arthrogryposis multiplex congenita).
- Tongue fasciculations strongly suggest SMA, but their absence does not exclude the diagnosis.
Spinal Muscular Atrophy - tests
Spinal Muscular Atrophy - lab
- Initial screening tests: Serum creatinine kinase may be mildly elevated.
- Genetic testing:
- Genetic testing of DNA extracted from blood (SMN deletions): Now the gold standard in diagnosis, may be done prenatally, >95% sensitive
- Genetic testing for Prader–Willi syndrome (fluorescence in situ hybridization and methylation) may be indicated if there is no SMN gene deletion and electromyography (EMG) is normal in an infant who appears to have SMA.
- Other testing:
- EMG may be helpful if the clinical presentation is atypical for SMA or if genetic testing is negative. EMG shows high-amplitude, long-duration motor units with a reduced recruitment pattern.
- With the advent of molecular testing, muscle biopsy is rarely performed. Use when genetic testing is unrevealing. The characteristic findings are fiber-type grouping with generalized atrophy of muscle fibers.
- If the entire evaluation is negative, MRI of the spine may be indicated to evaluate for an anomaly or mass lesion.
Spinal Muscular Atrophy - differencial diagnosis
- Other genetic neuromuscular disorders include congenital muscular dystrophy, congenital myopathy, glycogen storage disorders, myotonic dystrophy, mitochondrial disease, congenital myasthenia gravis, and Prader–Willi syndrome.
- More acute course may suggest infant botulism or Guillain–Barré syndrome, although the latter is rare in this age group.
- Systemic disorders: Sepsis, meningitis, acute bowel syndromes
- SMA II differential: Congenital muscular dystrophy, congenital myopathy, and congenital myasthenia gravis
- SMA III differential includes Duchenne, Becker, and the limb girdle muscular dystrophies.
- Spinal cord mass lesion may rarely resemble SMA.
Spinal Muscular Atrophy - TREATMENT
Spinal Muscular Atrophy - general measures
- Physical therapy is appropriate, although it may not affect the course of SMA I (most helpful in SMA types II and III).
- A wheelchair will maintain mobility in SMA type II. Adults with SMA III may require the use of a wheelchair later in their course.
- Spinal fusion surgery may preserve respiratory function.
- Low threshold for empiric antibiotics for respiratory infection is appropriate. Chest physiotherapy can help prevent pneumonia and atelectasis.
- Noninvasive positive-pressure ventilation ([BiPAP] and other regimens) may improve quality of life and life expectancy in patients with decreased respiratory function. More aggressive respiratory management is becoming more common and accepted among families and physicians, but the extent of interventions varies widely.
- Avoiding catabolic state with proactive nutritional support, including tube feeding.
Spinal Muscular Atrophy - FOLLOW UP
Spinal Muscular Atrophy - prognosis
- Most children with SMA type I die by 2 years without major pulmonary interventions. With ventilatory support, patients may survive several years longer; survival as long as two decades has been observed with tracheostomy and full mechanical ventilation.
- Children with SMA type II typically survive into late adolescence or early adulthood; this life expectancy is increasing with more aggressive pulmonary management.
- Individuals with SMA type III survive well into adulthood, and often have a normal life expectancy. In SMA type IIIa, ~2/3 of affected individuals cannot walk independently by age 40. In SMA type IIIb, only 1/3 of patients lose the ability to walk by age 40.
- Intelligence is generally preserved.
- Death typically ensues from respiratory complications. Discuss the level of respiratory interventions, including resuscitation, early in SMA I and in the advanced stages of SMA II and III.
Spinal Muscular Atrophy - complications
- Recurrent pneumonias, hypoventilation
- Swallowing difficulties may require tube feeding.
- Scoliosis may require surgery.
Spinal Muscular Atrophy - bibliography
- Hardart MKM, Truog RD. Spinal muscular atrophy—type I. Arch Dis Child. 2003;88:848–850.
- Hirtz D, Iannaccone S, Heemskerk J, et al. Challenges and opportunities in clinical trials for spinal muscular atrophy. Neurology. 2005;65:1352–1357.
- Iannaccone ST, Burghes A. Spinal muscular atrophies. Adv Neurol. 2002;88:83–98.
- Nicole S, Diaz CC, Frugier T, et al. Spinal muscular atrophy: Recent advances and future prospects. Muscle Nerve. 2002;26(1):4–13.
- Prasad AN, Prasad C. The floppy infant: Contribution of genetic and metabolic disorders. Brain Dev. 2003;25(7):457–476.
- Sumner CJ, Huynh TM, Markowitz JA, et al. Valproic acid increases SMN levels in spinal muscular atrophy patient cells. Ann Neurol. 2003;54:647–654.
- Zerres K, Rudnik-Schoneborn S. Natural history in proximal spinal muscular atrophy. Clinical analysis of 445 patients and suggestions for a modification of existing classifications. Arch Neurol. 1995;52(5):518–523.
Spinal Muscular Atrophy - CODES
Spinal Muscular Atrophy - icd9
335.10 Spinal muscular atrophy, unspecified
Spinal Muscular Atrophy - PATIENT TEACHING-MED
- Families of SMA: http://www.fsma.org
- Fight SMA: www.fightsma.org
- Muscular Dystrophy Association: http://www.mdausa.org
- Spinal Muscular Atrophy Foundation: www.smafoundation.org
Spinal Muscular Atrophy - FAQ
- Q: Can routine vaccinations be given to children with SMA?
- A: Yes. In addition to routine vaccinations, yearly influenza vaccinations are recommended for older children.
- Q: How much respiratory support should a child with SMA receive?
- A: Standards of care are evolving rapidly, and a consensus remains elusive. However, noninvasive respiratory interventions are becoming more widely accepted. Noninvasive respiratory options should be offered to all patients with SMA I and those in the later stages of SMA II. Tracheostomy is more controversial.
- Q: Are more effective therapies for SMA being developed?
- A: There are ongoing studies in animal models and proposed studies on humans, involving both pharmacologic and gene-based therapies. The Muscular Dystrophy Association and other groups are sources of information on such research.
Book Source Details
- Book Title: The 5-Minute Pediatric Consult
- Author(s): M. William Schwartz MD; et al.
- Year of Publication: 2008
- Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.
More About Congenital SMA with arthrogryposis
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: The 5-Minute Pediatric Consult
Authors: M. William Schwartz MD; et al.
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7577-9
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