Spinal Muscular Atrophy

Question 1

SMA is a ___ condition

Answer 1

rare genetic

Question 2

SMA is caused by:

Answer 2

mutations or deletions in the SMN1 gene

Question 3

Around 1 in ___ births

Answer 3

14,700

Question 4

SMA characterized by:

Answer 4

Motoneuronal death
Progressive muscle denervation
Skeletal muscular atrophy
Overall weakness
Loss of motor function

Question 5

___ muscles are usually more affected in SMA

Answer 5

Proximal

Question 6

Inheritance Type:

Answer 6

Autosomal Recessive

A child must inherit two copies of the mutated SMN1 gene (one from each parent) to be affected.

Carriers (one mutated SMN1 + one functional) do not show symptoms, but can pass the mutation on.

Question 7

From Carrier Parents: Risk Breakdown per Child

Each child of two carriers has:

Answer 7

25% chance of being affected (SMA)

50% chance of being a carrier

25% chance of being unaffected (no mutation)

Question 8

SMN1 vs SMN2

Answer 8

While SMN1 deletion causes SMA, the number of SMN2 “backup” genes influences severity:

Fewer SMN2 copies → more severe SMA (e.g., Type 1)

More SMN2 copies → milder SMA (e.g., Type 3)

Question 9

Motoneuron Death =

Answer 9

Degeneration of anterior horn cells in the spinal cord (LMN lesion)

Question 10

Progressive Muscle Denervation =

Answer 10

Leads to fasciculations, hypotonia, and progressive atrophy

Especially noticeable in proximal muscle groups

Expect atrophy, fasciculations, ↓ reflexes

Question 11

Proximal > Distal Weakness

Answer 11

Shoulder girdle (deltoids, biceps, triceps)

Trunk muscles (erector spinae, abdominals)

Pelvic girdle and thigh muscles (glutes, hip flexors/extensors)

📌 Distal muscles (hands, feet) are typically spared until later stages, especially in Types 2 and 3.

Question 11

Functional Consequences =

Answer 11

Poor head/trunk control in infants

Difficulty with antigravity movements (rolling, sitting, walking)

Progressive scoliosis or contractures

High fall risk in ambulatory individuals (Type 3)

Respiratory muscle involvement in severe forms (Type 1)

Question 12

LMN signs =

Answer 12

No spasticity or clonus; instead flaccid tone

Question 13

System-by-System Breakdown of SMA Signs & Symptoms:

Answer 13

Nervous system
**Lungs
Gastrointestinal
**Skeleton and muscle
Heart

Question 14

Nervous System Signs & Symptoms:

Answer 14

Impaired motor function

⬅️ Due to anterior horn cell degeneration

Presents as hypotonia, weakness, poor postural control

Question 15

Lungs Signs & Symptoms:

Answer 15

Breathing difficulties
Respiratory infections
Chest infections
Respiratory failure (especially in Type 1)

PT Implications:
Monitor respiratory rate, chest expansion
Train caregivers in airway clearance, postural drainage
Assist with secretion management (e.g. cough assist, percussion)

Question 16

Gastrointestinal Signs & Symptoms:

Answer 16

Dysphagia

📌 Often seen in Type 1 SMA

Risk for aspiration

Work alongside SLPs for safe feeding strategies

Question 17

Skeleton and muscle Signs & Symptoms:

Answer 17

Muscle weakness
Fatigue
Spasticity (rare in SMA, possibly a mislabel; usually LMN = hypotonia)
Bone fractures (due to decreased loading)
Contractures
Hip dislocation
Scoliosis
Kyphosis

📌 PT Role:

ROM programs, orthotics, serial casting

Seating and positioning to prevent spine deformities

Weight-bearing activities to support bone health

Question 18

Heart Signs & Symptoms:

Answer 18

Cardiomyopathy

⬅️ Especially in rare subtypes or severe cases

📌 PT Consideration:
Monitor vitals during activity, especially if cardiac symptoms are present

Question 19

historical classification of Spinal Muscular Atrophy (SMA)

Answer 19

age of onset, motor milestones, and life expectancy

Question 20

Instead of classifying by number (Type I, II, etc.), we’re starting to group patients more by functional phenotype, such as:

Answer 20

Non-sitters

Sitters

Walkers

Why? Because therapeutic interventions (like Spinraza or Zolgensma) can dramatically alter the disease trajectory.

Some infants with early-onset SMA are now gaining milestones once thought impossible.

Question 21

SMA type 0:

Answer 21

congenital

age of onset: in utero

motor ability: arthrogryposis multiplex congenita, severe respiratory insufficiency

survival: death within weeks

Question 22

SMA type I:

Answer 22

Infantile
(Werdig-Hoffman disease)

age of onset: < 6 months

motor ability: severe hypotonia, never able to sit

survival: death/ventilation by 2 years

Question 23

SMA type II:

Answer 23

Intermediate
(Dubowitz disease)

age of onset: >6 months to <18 months

motor ability: proximal weakness, able to sit, never able to walk

survival: survival into adulthood, albeit with substantial disability

Question 24

SMA type III:

Answer 24

Juvenile (Kugelberg-Welander disease) age of onset: > 18 months motor ability: proximal weakness, able to walk, may lose ability survival: normal

Question 25

SMA type IV:

Answer 25

Adult age of onset: >30 years motor ability: mild motor impairment survival: normal

Question 26

of SMN2 Copies & severity: 1-2

Answer 26

Severe (Type 1 or 0)

Question 27

of SMN2 Copies & severity: 3

Answer 27

Moderate (Type 2)

Question 28

of SMN2 Copies & severity: 4+

Answer 28

Milder (Type 3 or 4)

Question 29

📌 SMN2 = "Backup" gene:

Answer 29

The more copies, the more SMN protein produced, and the milder the phenotype

Question 30

First Period: 1891–1995 (104 years) Key event:

Answer 30

1891: First clinical case report by Werdnig Characterized by clinical diagnosis and classification only No known cause or treatment — care was palliative

Question 31

Second Period: 1995–2016 (21 years) Key event:

Answer 31

1995: Discovery of SMN1 and SMN2 genes Launched a wave of drug discovery and repurposing research Foundations laid for gene-targeted therapy development

Question 32

Third Period: 2016–Present (7+ years) Key event:

Answer 32

2016: FDA approval of Nusinersen (Spinraza) — first disease-modifying therapy for SMA Now includes: Gene therapy (Zolgensma) Oral SMN2 upregulators (Risdiplam) Newborn screening in most U.S. states 2018: States began to screen for SMA at birth

Question 33

three major FDA-approved treatments:

Answer 33

Antisense oligonucleotides (ASOs) Gene Therapy Small Molecule Drug

Question 34

Spinraza (Nusinersen) =

Answer 34

Antisense oligonucleotide (ASO) Increases SMN protein production by modifying SMN2 mRNA splicing Eligibility: Prenatal 25 weeks to adulthood = all ages Delivery: Intrathecal injection (via lumbar puncture) every 4 months Common in Type 1 and 2 SMA patients

Question 35

Zolgensma (Onasemnogene abeparvovec) =

Answer 35

Gene therapy Delivers a functional SMN1 gene via AAV9 viral vector (permanent) Eligibility: Prenatal 35 weeks to 2 years old = ≤2 years Delivery: Single IV infusion ideal for early intervention (esp. pre-symptomatic Type 1 infants)

Question 36

Evrysdi (Risdiplam) =

Answer 36

Small molecule drug Boosts SMN2 gene expression by enhancing splicing Eligibility: 2 months to adulthood = ≥2 months Delivery: Daily oral liquid Suitable for non-ambulatory older children or adults with SMA Type 2 or 3

Question 37

Non-Sitters Clinical Course:

Answer 37

(Typically SMA Type 1 or severe Type 2) Clinical Features: Postural instability (especially head/neck) Limb, neck, jaw contractures Chest wall deformities → impaired breathing Plagiocephaly (due to positioning) Pain Hip dislocation Skin breakdown Poor endurance & mobility High fracture risk Impaired pulmonary function = most critical risk

Question 38

Non-Sitters PT Focus:

Answer 38

Positioning, respiratory support, adaptive seating PROM, orthotic support, pain prevention Maximize comfort & pulmonary care Resp failure, skin, posture

Question 39

Sitters Clinical Course:

Answer 39

(Typically SMA Type 2) Clinical Features: Postural instability (especially head/neck) Limb, neck, jaw contractures Chest wall deformities → impaired breathing Impaired mobility Impaired pulmonary function Scoliosis and pelvic obliquity Deformed feet Hand tremors Fractures due to lack of WB and osteopenia

Question 40

Sitters PT Focus:

Answer 40

Maintain sitting posture, manage scoliosis Standing frames, supported standing for bone health Adaptive equipment for ADLs

Question 41

Walkers Clinical Course:

Answer 41

(Typically SMA Type 3 and mild Type 2 with treatment) Clinical Features: Asymmetric muscle weakness Impaired mobility Poor muscle endurance Falls, balance issues Contractures, stiffness Hand tremors (fine motor difficulty) Still at risk for fractures

Question 42

Walkers PT Focus:

Answer 42

Strength/endurance training Fall prevention, mobility aids as needed Monitor for regression or need for bracing Preserve ambulation & strength

Question 43

Tests and Measures Non-Sitters =

Answer 43

Strength: MMT, HHD ROM: To track/prevent contractures Pulmonary: FVC, MIP/MEP → baseline & respiratory decline CHOP INTEND HINE-2

Question 44

Tests and Measures Sitters =

Answer 44

Strength & pulmonary testing continues Assess upper limb and trunk function HINE-2 (early tracking) RHS (Revised Hammersmith Scale) MFM-20 (Motor Function Measure) RULM (Revised Upper Limb Module)

Question 45

Tests and Measures Walkers =

Answer 45

Timed Function Tests: 6MWT: Endurance 10mWT: Speed TUG: Functional mobility & balance RHS MFM-20 RULM

Question 46

CHOP INTEND

Answer 46

(Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders) Population: Infants with severe weakness (Type 1 SMA) Focus: Head/trunk control, spontaneous movement, antigravity movement Used to evaluate potential for new SMA treatments PT Tip: Improves with early treatment; sensitive to subtle changes 16 items scored from 0-4 with a maximum of 64 points

Question 47

HINE-2

Answer 47

(Hammersmith Infant Neurological Exam Section 2) Population: Infants <24 months with neuromuscular disorders Items: 8 motor milestones (head control, sitting, standing, etc.) Use: Tracks developmental progression over time PT Tip: Often used alongside CHOP INTEND in infants post-therapy

Question 48

RHS

Answer 48

(Revised Hammersmith Scale) Developed for very weak SMA type 2 to very strong SMA type 3 33 items with grades of 0, 1 and 2 (transfers, sitting balance, antigravity leg control) Assesses gross motor skills like sitting, standing, transfers, and walking. PT Tip: Sensitive to loss of function and improvement

Question 49

MFM-20

Answer 49

(Motor Function Measure) MFM-20 for kids <7 or non-ambulatory MFM-32 for older ambulatory kids/adults tems: 20 or 32 tasks, across 3 domains: D1: Standing/transfers D2: Axial/proximal motor D3: Distal motor PT Tip: Great for longitudinal tracking of function loss/gain

Question 50

RULM

Answer 50

(Revised Upper Limb Module) Developed for very weak SMA type 2 to very strong SMA type 3 Assesses motor performance in the upper limbs Items: 20 items – reach, grip, lift, stabilize PT Tip: Important in school-aged kids who use arms for mobility aids or transfers

Question 51

Gold standard for tracking motor function in non-sitters, especially those receiving Zolgensma or Spinraza

Answer 51

CHOP INTEND

Question 52

Tracks developmental progression over time

Answer 52

HINE-2

Question 53

Global assessment of functional mobility across disease spectrum

Answer 53

MFM-20 / MFM-32

Question 54

Specifically captures UE function, helpful when LE is more affected

Answer 54

RULM

Question 55

Tracks motor function changes in sitters, especially on Spinraza/Evrysdi

Answer 55

RHS

Question 56

Timed Function Tests (Walkers only):

Answer 56

6MWT (6-Min Walk Test): Endurance 10mWT: Walking speed TUG: Balance, functional mobility

Question 57

Functional assessment of strength designed for infants with neuromuscular disorders.

Answer 57

CHOP INTEND

Question 58

CHOP INTEND Items include:

Answer 58

Spontaneous movement of UEs/LEs Hand grip Head control Shoulder and hip movement Rolling and leg flexion Focuses on antigravity movement, midline control, and basic motor responses Baseline assessment Tracking disease progression or treatment response (Spinraza, Zolgensma, Evrysdi) Paired with HINE-2 for more detailed neuro screen

Question 59

Revised Hammersmith Scale (RHS) is a revision of:

Answer 59

Revision of the Hammersmith Functional Motor Scale Expanded (HFMSE)

Question 60

Revised Hammersmith Scale (RHS) Items Include:

Answer 60

Sitting unsupported Hands to head while sitting Sitting to lying (controlled) Hip adduction in crook-lying Hip flexion in supine Lifting head from supine Includes gross motor, postural, and anti-gravity tasks — from sitting to more advanced supine/standing transitions

Question 61

Used for longitudinal tracking, especially to measure change in response to treatments like Spinraza or Evrysdi.

Answer 61

RHS

Question 62

Revised Upper Limb Module (RULM) Items Include:

Answer 62

B. Bring hands from lap to table C. Trace path with pencil D. Pick up tokens E. Place token into cup Shoulder-level task performance (like token in vertical cup) reflects higher motor function demand and is often the most challenging. 0 = No/minimal function 1 = Partial function 2 = Full/Functional performance

Question 63

Interdisciplinary SMA Care Model:

Answer 63

Pulmonary Acute Care Other Organ Involvement Medication Nutrition/GI/Bone Health Orthopedic Neuromuscular/Rehabilitation

Question 64

Pulmonary:

Answer 64

Respiratory support, non-invasive ventilation, suctioning, infection prevention

Question 65

Acute Care:

Answer 65

Monitoring during illness or surgeries, emergency care planning

Question 66

Other Organ Involvement:

Answer 66

Monitoring for rare complications in renal, hepatic, etc.

Question 67

Medication:

Answer 67

Access to disease-modifying therapies (e.g., Spinraza, Zolgensma, Evrysdi)

Question 68

Nutrition/GI/Bone Health:

Answer 68

Managing dysphagia, GI motility, and bone density (vitamin D, calcium)

Question 69

Orthopedic:

Answer 69

Managing scoliosis, hip dislocation, and contractures

Question 70

Neuromuscular/Rehabilitation:

Answer 70

PT/OT for motor function, endurance, posture, equipment fitting

Question 71

landmark 2018 publication on SMA diagnosis and management Key takeaways from this paper include:

Answer 71

Importance of early diagnosis (preferably via newborn screening) A strong recommendation for rehabilitation-centered care to preserve function Regular assessments of ROM, strength, pulmonary capacity, and nutrition Guidance for intervention timing, including bracing, therapy, and drug therapy alignment The need for standardized outcome tools by phenotype (CHOP-INTEND, HINE-2, RHS, MFM-20, RULM)

Question 72

PT Management for Non-Sitters:

Answer 72

Tummy Time Early WB in stander Contracture prevention Positioning and bracing Tummy time - Promotes head control, cervical extension, and weight-bearing through upper extremities Early WB in stander - Encourages bone density, supports hip joint development, and improves cardiopulmonary function Contracture prevention - Uses passive range of motion (PROM), stretching, and orthotics (e.g. AFOs or hand splints) to prevent joint stiffness and improve alignment Positioning and bracing - Supports posture, delays progression of scoliosis and hip dislocation, and facilitates safe and functional positioning in seating/lying systems

Question 73

PT Management for Sitters:

Answer 73

Strengthening Transitional Movements Contracture Prevention Strengthening - Focus on antigravity trunk and upper extremity muscles to maintain postural control, functional reach, and independence in ADLs Transitional Movements - Encourage bed mobility, transfers, sit-to-supine, and controlled movement transitions to support independence and prevent deconditioning Contracture Prevention - Regular PROM, stretching, and splinting/bracing to prevent hip/knee/elbow contractures and improve long-term seating tolerance and posture

Question 74

PT Management for Walkers:

Answer 74

Strength and endurance training Transitional movements Fall recovery activities Strength and endurance training - Submaximal, low-resistance activities (e.g., aquatic therapy, biking, walking) to promote cardiopulmonary endurance and maintain lower extremity strength without inducing fatigue Transitional movements - Practice movements like floor to stand, sit to stand, and transfers to promote independence and reduce fall risk Fall recovery activities - Train safe falling techniques, floor mobility, and strategies for rising from the floor independently or with minimal assist

Question 75

SMA is caused by a ___ gene mutation or deletion and results in ___ with ___ muscles being more affected than ___ muscles

Answer 75

SMN1 muscle atrophy proximal distal

Question 76

___ difficulties and ___ infections are common with this diagnosis

Answer 76

Breathing respiratory

Question 77

SMA classification is currently being re-written due to ____

Answer 77

all of the recent drug therapy advances

Question 78

The PTs primary role is to work on:

Answer 78

positioning transitional movements strengthening contracture prevention weight bearing activities

Question 79

Due to weakened ___ and ___, ___is a hallmark—especially in severe types.

Answer 79

intercostals diaphragm respiratory compromise