Clinical presentation for spinal muscular atrophy includes a wide range of phenotypes which are classified into groups based on age of onset and maximum level of motor function achieved, but hypotonia and/or muscle weakness and atrophy are common signs and symptoms. 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 (age at onset)

0-6 MONTHS (infantile-onset) 

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

Highest motor milestone achieved

UNABLE TO SIT
(“nonsitters”)

Life expectancy
(untreated SMA)

≤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 (later-onset) 

7-18 MONTHS (later-onset)2,4,6-9

Highest motor milestone achieved

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

Life expectancy
(untreated SMA)

>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+ (late-onset) 

18 MONTHS+ (late-onset)1,2,5,8,10

Highest motor milestone achieved

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

Life expectancy
(untreated SMA)

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
(untreated SMA)

NORMAL

Phenotype

Type IV

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

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.

Disease progression in SMA may be divided into 3 conceptual phases:
preclinical, subacute, and chronic12

Acquisition of gross motor milestones in typically developing children
compared with individuals with SMA12

Adapted from Swoboda et al, 2007.12

Preclinical phase:

individuals with SMA may appear to develop normally12

  • 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 threshold12

  • 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 plateau12

  • 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

Functional decline in later-onset SMA may be associated with the maximal function achieved

In a study of patients (n=159) with later-onset (Type II and Type III) SMA, maximum level of function achieved was assessed relative to the age at onset of symptoms.13

Median age at which patients lost the ability to walk independently based on age of onset13

Percentage of patients

Age at onset

Median age at loss of ability to walk independently (n=59)

Percentage of patients

50%

Age at onset

< 2 years

Median age at loss of ability to walk independently (n=59)

12 years of age

Percentage of patients

50%

Age at onset

> 2 years

Median age at loss of ability to walk independently (n=59)

44 years of age (P=0.001)

  • 50% of patients whose best function was walking with assistance lost this ability by age 7 (median)13
    • 0% of these patients could walk after age 14
    • As walking was lost, the ability to raise their hands above their heads was also lost
  • Patients whose highest level of function was sitting independently maintained the ability until age 14 (median)13

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)14:

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%

Stabilization 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 stabilize. These included14:

  • 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 stabilize.

97% of the respondents with later-onset (Types II and III) SMA reported that stabilization of the level of function would represent progress14

Learn more about measures of motor function in SMA.

REFERENCES 

1. Prior TW, Finanger E. Spinal muscular atrophy. NCBI Bookshelf website.. Updated December 22, 2016. Accessed September 12, 2018. 2. Mercuri E, Finkel RS, Muntoni F, et al; SMA Care Group. Diagnosis and management of spinal muscular atrophy: part 1: recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscul Disord. 2018;28(2):103-115. 3. MedlinePlus. Medical Encyclopedia. https://medlineplus.gov/encyclopedia.html. Updated April 12, 2017. Accessed April 12, 2017. 4. Markowitz JA, Singh P, Darras BT. Spinal muscular atrophy: a clinical and research update. Pediatr Neurol. 2012;46(1):1-12. 5. Muscular Dystrophy Association. Spinal muscular atrophy. Types of SMA. https://www.mda.org/disease/spinal-muscular-atrophy/types. Accessed March 15, 2017. 6. 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. 7. Lunn MR, Wang CH. Spinal muscular atrophy. Lancet. 2008;371(9630):2120-2133. 8. Moosa A, Dubowitz V. Motor nerve conduction velocity in spinal muscular atrophy of childhood. Arch Dis Child. 1976;51(12):974-977. 9. 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. Updated September 26, 2016. Accessed March 28, 2017. 10. 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. 11. 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. 12. Swoboda KJ, Kissel JT, Crawford TO, et al. Perspectives on clinical trials in spinal muscular atrophy. J Child Neurol. 2007;22(8):957-966. 13. Russman BS, Buncher CR, White M, Samaha FJ, Iannaccone ST; the DCN/SMA Group. Function changes in spinal muscular atrophy II and III. Neurology. 1996;47(4):973-976. 14. Rouault F, Christie-Brown V, Broekgaarden R, et al. Disease impact on general well-being and therapeutic expectations of European type II and type III spinal muscular atrophy patients. Neuromuscul Disord. 2017;pii:S0960-8966(16)31129-4. doi:10.1016/j.nmd.2017.01.018.

How might the basic function and progression of an individual with SMA determine daily activities and lifestyle?

Learn more