Clinical presentation for SMA 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 symptoms:2

  • 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 (age at onset)

Type I (also known as Werdnig-Hoffmann disease) 

Age of onset

0-6 MONTHS
(infantile-onset)1,2,4,5

Highest motor milestone achieved

UNABLE TO SIT
(“non-sitters”)

Life expectancy

2 YEARS

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

 

 

 

 

Type II (also known as Dubowitz disease) 

Age of onset

7-18 MONTHS
(later-onset)2-5

Highest motor milestone achieved

ABLE TO SIT INDEPENDENTLY
(“sitters”, although they may lose this ability by the mid-teenage years)

Life expectancy

>2 YEARS
70% still living
at age 25

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

 

 

 

 

 

Type III (also known as Kugelberg-Welander disease) 

Age of onset

18+ MONTHS
(late-onset)1,2

Highest motor milestone achieved

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

Life expectancy

NORMAL

Clinical characteristics

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

 

 

 

 

 

 

 

Type IV 

Age of onset

LATE ADOLESCENCE/
ADULTHOOD

(adult-onset)1,2

Highest motor milestone achieved

ALL

Life expectancy

NORMAL

Clinical characteristics

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

 

 

 

 

 

 

 

 

 

Time to diagnosis is critical – earlier diagnosis and intervention may help improve the outcomes for individuals with SMA.6

If you see symptoms of SMA in your patient, refer immediately for an urgent appointment with a paediatric neurologist.

Disease progression in SMA may be divided into 3 conceptual phases:
preclinical, subacute, and chronic7

Acquisition of gross motor milestones in typically developing children compared with individuals with SMA7

Adapted from Swoboda et al, 2007.7

Preclinical phase:

individuals with SMA may appear to develop normally7

  • Motor unit loss progresses, but collateral reinnervation may mask symptoms
  • May be rapid in infantile-onset (Type I) SMA
    • Severe denervation may occur by 6 months of age
  • In later-onset (Type II and Type III) SMA, the preclinical phase may last for months or years in mildly affected individuals

Subacute phase:

motor unit loss may reach a critical threshold7

  • Rapid motor-unit loss associated with significant reductions to the maximum compound muscle action potential (CMAP) amplitudes over a period of weeks to months
  • May be exacerbated by illness, nutritional compromise, or growth
  • Clinical symptoms may evolve:
    • Weakness and progressive paralysis in infantile-onset SMA
    • Loss of the ability to sit or roll may be seen in severe later-onset (Type II) SMA
    • Slowing of acquisition of expected gross motor milestones in less affected individuals with Types II or III SMA

Chronic phase:

motor unit loss may appear to plateau7

  • Functional motor abilities may remain stable for months or years
  • Motor skills that were previously lost, such as rolling, may return or the individual may slowly acquire some additional gross motor skills
  • Denervation progresses with age

Loss of function in later-onset SMA may have a major impact on quality of life

In a European survey of 822 individuals (8-73 years of age) with later-onset (Type II and Type III) SMA, a subgroup of patients identified their current functional abilities that if lost would affect their quality of life (QoL):8

Loss of functional ability
that would affect QoL

Patients currently able
to perform function

Using restroom alone

72%

Washing oneself

64%

Performing transfers on his/her own

61%

Feeding self

60%

Dressing self

56%

Stabilisation of functional abilities may be important to individuals with later-onset SMA

In the same survey, individuals with later-onset SMA identified those functional abilities that they have retained and would most want to stabilise. These included:8

  • Feeding him/herself
  • Washing independently 
  • Using restroom independently 
  • Performing transfers independently
  • Using a keyboard
  • Turning in bed
  • Writing with a pen
  • Brushing his/her teeth
  • Dressing by him/herself
  • Brushing his/her hair

Participants were asked to choose the 3 functions, ranked 1 through 3, in decreasing order of priority they would most like to stabilise.

REFERENCES 

1. Prior TW, Finanger E. Spinal muscular atrophy. NCBI Bookshelf Web site. http://www.ncbi.nlm.nih.gov/books/NBK1352/report =printable. Updated December 22, 2016. Accessed October 2017. 2. Wang CH, et al. J Child Neurol. 2007;22:1027–49. 3. Darras BT, et al. Neuromuscular Disorders of Infancy, Childhood, and Adolescence: A Clinician’s Approach. 2nd ed. London, UK: Elsevier; 2015. 4. Lunn MR and Wang CH. Lancet. 2008;371:2120–33. 5. NIH National Center for Advancing Translational Sciences. Genetic and Rare Diseases Information Center. Spinal muscular atrophy type 2. https://rarediseases.info.nih.gov/diseases/4945/spinal-muscular-atrophy-type-2.  Accessed October 2017. 6. Rothwell E, et al. Am J Med Genet A. 2013;161A:679–86. 7. Swoboda KJ, et al. J Child Neurol. 2007;22:957–66. 8. Rouault F, et al. Neuromuscul Disord. 2017;27:428–38.