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Signs and symptoms of spinal muscular atrophy (SMA)

Spinal muscular atrophy is a single-gene disease with a spectrum of clinical presentation1,2

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Clinical presentation for spinal muscular atrophy may differ according to the age of onset and severity, but hypotonia (floppy baby syndrome) and/or muscle weakness and atrophy are common signs or symptoms2,3:

  • Weakness is usually symmetrical
  • Weakness is more proximal than distal
  • Sensation is preserved
  • Tendon reflexes are absent or diminished
  • Weakness is greater in the legs than the arms
  • Severity of weakness generally correlates with the age of onset

Characteristics of spinal muscular atrophy

0-6 MONTHS (infant-onset) 

0-6 MONTHS (infant-onset)1,2,4

Highest motor milestone achieved

UNABLE TO SIT
(“nonsitters”)

Life expectancy

≤2 YEARS

Phenotype

TYPE I
(also known as Werdnig-Hoffmann disease)

Clinical characteristics

  • Hypotonia and impaired head control
  • “Frog leg” presentation
  • Weak cry
  • Weak cough
  • Swallowing, feeding, and handling of oral secretion are affected before 1 year of age
  • Atrophy and fasciculation of the tongue
  • Weakness and hypotonia in the limbs and trunk
  • Intercostal muscle weakness (note, the diaphragm is initially spared)
  • Paradoxical breathing
  • Bell-shaped trunk with chest wall collapse and abdominal protrusion

To learn how different aspects of care may relate
to the signs and symptoms of SMA, click here.

7-18 MONTHS (intermediate) 

7-18 MONTHS (intermediate)2,4-6

Highest motor milestone achieved

ABLE TO SIT INDEPENDENTLY (“sitters”)

Life expectancy

>2 YEARS
70% STILL LIVING AT AGE 25

Phenotype

TYPE II
(also known as Dubowitz disease)

Clinical characteristics

  • Bulbar weakness with swallowing difficulties that may lead to poor weight gain
  • Weak intercostal muscles
  • Diaphragmatic breathing
  • Difficulty coughing and clearing tracheal secretion
  • Fine tremors with extended fingers or when attempting hand grips
  • Kyphoscoliosis, or scoliosis requiring bracing or spinal surgery
  • Joint contractures

To learn how different aspects of care may relate
to the signs and symptoms of SMA, click here.

18 MONTHS+ (juvenile-onset) 

18 MONTHS+ (juvenile-onset)1,2,7

Highest motor milestone achieved

ABLE TO WALK INDEPENDENTLY (“walkers”, although they may progressively lose this ability)

Life expectancy

NORMAL

Phenotype

TYPE III
(also known as Kugelberg-Welander disease)

Clinical characteristics

  • Scoliosis
  • Swallowing difficulty
  • Cough, and nocturnal hypoventilation
  • Muscle aching
  • Joint overuse symptoms

To learn how different aspects of care may relate
to the signs and symptoms of SMA, click here.

LATE ADOLESCENCE/ ADULTHOOD (adult-onset) 

LATE ADOLESCENCE/ADULTHOOD (adult-onset)1,2,4

Highest motor milestone achieved

ALL

Life expectancy

NORMAL

Phenotype

TYPE IV

Clinical characteristics

  • Physical symptoms are similar to juvenile-onset SMA, with the gradual onset of weakness, tremor, and muscle twitching first noted in late teens or adulthood

To learn how different aspects of care may relate
to the signs and symptoms of SMA, click here.

DHMN* (adolescent-onset) 

DHMN* (adolescent-onset)8-10

Highest motor milestone achieved

ALL

Life expectancy

NORMAL

Phenotype

TYPE V

Clinical characteristics

  • Muscular weakness and wasting is first seen in the upper limbs
  • Eventually, half of patients develop weakness in the lower limbs
*Although the literature often groups this condition with spinal muscular atrophy, it does not share the same genetic cause as spinal muscular atrophy.9

To learn how different aspects of care may relate
to the signs and symptoms of SMA, click here.

DHMN=distal hereditary motor neuropathy.

Note: You may see these characteristics of spinal muscular atrophy more commonly grouped by “Type” (I-V) in internet articles or clinical research.

The natural course of spinal muscular atrophy is characterised by progressive muscle atrophy and loss of motor function5,6,8

A number of motor function scales have been developed that are useful for quantifying the natural history of spinal muscular atrophy, as well as response to investigational therapeutic agents in clinical trials.11-13

Examples include†:

The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) is used to evaluate the motor skills of infants with spinal muscular atrophy11,14:

  • Includes contains 16 items used to assess motor skills
  • Each item is graded on a scale of 0-4, where 0 represents no response to a particular test, and 4 represents a complete response
  • Total score ranges from 0-64
symptoms-spinal-muscular-atrophy symptoms-spinal-muscular-atrophy

The Hammersmith Infant Neurological Examination (HINE) is a motor function assessment tool designed to be a simple method for evaluating motor skills in infants from 2 months to 2 years of age12,15:

  • Exam includes 26 items that provide a comprehensive assessment of an infant’s neuromuscular development
    —Each item is scored from 0 to 3, with a total possible score of 78
  • The motor milestones portion of the HINE includes 8 items
Spinal Muscular Atrophy Symptoms Spinal Muscular Atrophy Symptoms

The Hammersmith Functional Motor Scale—Expanded (HFMSE) is a validated measure that has been used in several clinical trials to evaluate the motor function of children with spinal muscular atrophy. The HFMSE adds 13 clinically relevant items from the Gross Motor Function Measure (GMFM) related to lying/rolling, crawling, crawling/kneeling, standing, and walking/running/jumping13,16:

  • Exam has 33 items that are scored on a scale of 0-2
  • Total score ranges from 0 to 66, with lower scores indicating poorer motor function
Hammersmith Functional Motor Scale Hammersmith Functional Motor Scale

Child depicted in graphic above is ≥2 years of age.

†This is not a comprehensive list of motor function scales.



In spinal muscular atrophy, electrophysiologic measurements may be used to assess the health of motor neurons17

  • Compound muscle action potential (CMAP) response is a measure of the electrophysiologic output from a specific muscle or muscle group following stimulation of a peripheral nerve18
  • Motor unit number estimation (MUNE) is a method that estimates the number of motor units supplying a specific muscle. MUNE values are calculated from the ratio of the maximal CMAP to the average single motor neuron potential (SMUP)
    • SMUP is measured by moving a stimulating electrode along a motor nerve at multiple points19

CMAP may decrease rapidly in some individuals with spinal muscular atrophy17

Reductions in CMAP are associated with the onset of symptoms in individuals with infantile-onset (Type I) spinal muscular atrophy17

Early diagnosis may be an important consideration in the treatment of spinal muscular atrophy20

The pattern of motor neuron loss seen in SMA suggests that a treatment for infantile-onset (Type I) SMA should be administered as early as possible, including the presymptomatic period before significant loss of motor neurons.20

REFERENCES 

1. Prior TW, Russman BS. Spinal muscular atrophy. NCBI Bookshelf Web site. http://www.ncbi.nlm.nih.gov/books/NBK1352/?report=printable. Updated November 14, 2013. Accessed April 15, 2016. 2. Wang CH, Finkel RS, Bertini ES, et al; and Participants of the International Conference on SMA Standard of Care. Consensus statement for standard of care in spinal muscular atrophy. J Child Neurol. 2007;22(8):1027-1049. 3. MedlinePlus. Medical Encyclopedia. https://www.nlm.nih.gov/medlineplus/encyclopedia.html. Updated April 21, 2016. Accessed April 25, 2016. 4. Markowitz JA, Singh P, Darras BT. Spinal muscular atrophy: a clinical and research update. Pediatr Neurol. 2012;46(1):1-12. 5. Darras BT, Royden Jones H Jr, Ryan MM, De Vivo DC, eds. Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician’s Approach. 2nd ed. London, UK: Elsevier; 2015. 6. Lunn MR, Wang CH. Spinal muscular atrophy. Lancet. 2008;371(9630):2120-2133. 7. Online Mendelian Inheritance in Man. Spinal muscular atrophy, Type III; SMA3. http://www.omim.org/entry/253400. Updated February 7, 2013. Accessed April 26, 2016. 8. Genetics Home Reference. SMN1. https://ghr.nlm.nih.gov/gene/SMN1. Published April 20, 2016. Accessed April 25, 2016. 9. Online Mendelian Inheritance in Man. Neuronopathy, distal hereditary motor, type VA; HMN5A. http://www.omim.org/entry/600794. Edited January 2, 2014. Accessed April 22, 2016. 10. Irobi J, Dierick I, Jordanova A, Claeys KG, De Jonghe P, Timmerman V. Unraveling the genetics of distal hereditary motor neuropathies. Neuromolecular Med. 2006;8(1-2):131-146. 11. Glanzman AM, Mazzone E, Main M, et al. The Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND): test development and reliability. Neuromuscul Disord. 2010;20(3):155-161. 12. Romeo DM, Ricci D, Brogna C, Mercuri E. Use of the Hammersmith Infant Neurological Examination in infants with cerebral palsy: a critical review of the literature. Dev Med Child Neurol. 2016;58(3):240-245. 13. Mercuri E, Finkel R, Montes J, et al. Patterns of disease progression in type 2 and 3 SMA: implications for clinical trials. Neuromuscul Disord. 2016;26(2):123-131. 14. Spinal Muscular Atrophy Clinical Research Center. CHOP INTEND for SMA Type I score sheet. http://columbiasma.org/links.html. Updated March 14, 2013. Accessed April 26, 2016. 15. Data on file. Biogen Inc, Cambridge, MA. 16. The Pediatric Neuromuscular Clinical Research Network for SMA. Expanded Hammersmith Functional Motor Scale for SMA (HFMSE). http://columbiasma.org/links.html. March 7, 2009. Accessed April 25, 2016. 17. Swoboda KJ, Prior TW, Scott CB, et al. Natural history of denervation in SMA: relation to age, SMN2 copy number, and function. Ann Neurol. 2005;57(5):704-712. 18. Arnold WD, Sheth KA, Wier CG, et al. Electrophysiological motor unit number estimation (MUNE) measuring compound muscle action potential (CMAP) in mouse hindlimb muscles. J Vis Exp. 2015;103:1-8. 19. Bromberg MB, Swoboda KJ. Motor unit number estimation in infants and children with spinal muscular atrophy. Muscle Nerve. 2002;25(3):445-447. 20. Finkel RS. Electrophysiological and motor function scale association in a pre-symptomatic infant with spinal muscular atrophy type I. Neuromuscul Disord. 2013;23(2):112-115.

How does the basic function and progression of a child with SMA determine daily activities and lifestyle?

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