Spinal Muscular Atrophy
Progressive Motor Neuron Disease
SMA Classification
Critical Must-Knows
- SMN1 Gene: Survival motor neuron gene mutation.
- Four Types: Based on age of onset and motor milestones.
- Scoliosis: Universal in Type I/II, common in Type III.
- New Therapies: Gene therapy and antisense oligonucleotides.
- Respiratory Care: Primary cause of mortality.
Examiner's Pearls
- "Know the SMA types and motor milestones
- "Scoliosis is nearly universal
- "Gene therapy has changed prognosis
- "Respiratory failure is the main cause of death
Gene Therapy Era
New disease-modifying therapies have dramatically changed the prognosis for SMA.
- Nusinersen (Spinraza): Antisense oligonucleotide. Intrathecal. Increases SMN2 expression.
- Onasemnogene (Zolgensma): Gene therapy. Single IV dose. Replaces SMN1.
- Early treatment (before symptom onset) leads to best outcomes.
- Orthopaedic manifestations may still occur but are less severe with early treatment.
SMA Types
| Type | Onset | Motor Milestones | Prognosis |
|---|---|---|---|
| Less than 6 months | Never sits | Death by 2 years without treatment | |
| 6-18 months | Sits, never walks | Survives to adulthood with support | |
| Greater than 18 months | Walks (may lose ability) | Normal or near-normal lifespan | |
| Adult onset | Walks | Mild, slowly progressive |
SMA Types
Memory Hook:I-II-III-IV: Infant, Intermediate, Late, Adult.
Orthopaedic Issues
Memory Hook:SHC - Scoliosis, Hips, Contractures.
Treatment Principles
Memory Hook:RSG - Respiratory, Scoliosis, Gene therapy.
Overview/Epidemiology
Spinal Muscular Atrophy (SMA) is a progressive neuromuscular disorder.
- Genetics: Autosomal recessive. Mutation/deletion in SMN1 (Survival Motor Neuron 1) gene on chromosome 5q.
- Incidence: 1 in 10,000 live births. Carrier frequency 1 in 50.
- Pathophysiology: Degeneration of anterior horn cells in the spinal cord leads to progressive weakness.
- Historical Significance: Leading genetic cause of infant death (prior to gene therapy).
Pathophysiology
Spinal Cord Pathology
- Anterior horn cells (lower motor neurons) degenerate.
- Results in denervation of skeletal muscles.
- Proximal muscles affected more than distal.
- Lower limbs typically weaker than upper limbs.
Why Scoliosis Develops
- Trunk muscle weakness leads to spinal collapse.
- Gravity + asymmetric weakness = progressive curve.
- Usually thoracolumbar, long sweeping C-curve.
- Pelvic obliquity is common.
Classification Systems
SMA Type I (Werdnig-Hoffmann Disease)
- Onset: Birth to 6 months.
- Motor Milestones: Never achieves sitting.
- Features: Severe hypotonia, frog-leg posture, paradoxical breathing.
- Prognosis: Without treatment, death by age 2 (respiratory failure).
- With Gene Therapy: Dramatically improved survival.
Clinical Assessment
History:
- Age of symptom onset.
- Motor milestones achieved and lost.
- Family history.
- Respiratory status.
Physical Exam:
- Hypotonia: Floppy infant (Type I).
- Weakness: Proximal greater than distal. Symmetric.
- Reflexes: Absent or diminished.
- Fasciculations: Tongue fasciculations are characteristic.
- Spine: Assess for scoliosis.
- Hips: Assess for dysplasia, contractures.
Investigations
Genetic Testing:
- SMN1 gene deletion/mutation: Confirmatory.
- SMN2 copy number: Prognostic (more copies = milder phenotype).
EMG/Nerve Conduction:
- Denervation pattern (rarely needed now with genetic testing).
Pulmonary Function:
- FVC (forced vital capacity) monitoring.
Imaging:
- Spine X-ray: Scoliosis assessment.
- Hip X-ray: Dysplasia, subluxation.
Management Algorithm
Medical Management
- Gene Therapy (Onasemnogene/Zolgensma): Single IV dose in infants.
- Nusinersen (Spinraza): Intrathecal injections every 4 months.
- Risdiplam (Evrysdi): Oral SMN2 splicing modifier.
- Respiratory Support: BiPAP, cough assist, suctioning.
- Nutritional Support: Gastrostomy if swallowing impaired.
Surgical Techniques
Posterior Spinal Fusion
Indications: Progressive scoliosis greater than 40-50 degrees with adequate pulmonary function.
Technique: Posterior approach. Long fusion from upper thoracic to pelvis (typically T2-pelvis). Pelvic fixation (iliac screws or S2-alar-iliac screws) is essential due to pelvic obliquity. Use of hybrid constructs or all-screw constructs.
Considerations: High perioperative risk due to respiratory compromise. Anesthesia team experienced in neuromuscular scoliosis is essential.
Complications
| Complication | Context | Management |
|---|---|---|
| Respiratory Failure | Primary cause of death | BiPAP, ventilation, cough assist |
| Progressive Scoliosis | Universal in Type I/II | Bracing, surgery |
| Hip Dysplasia | Common in Type I/II | Usually observation |
| Contractures | Hips, knees, feet | Stretching, splinting, releases |
| Perioperative Complications | High risk for scoliosis surgery | Experienced team, ICU care |
Postoperative Care
- ICU Admission: For scoliosis surgery.
- Respiratory: May require prolonged ventilation.
- Mobilization: Early sitting in wheelchair.
- Pain Management: Multimodal.
- Long-Term: Bracing discontinued after fusion. Ongoing respiratory and nutritional support.
Outcomes/Prognosis
- Type I (Untreated): Death by 2 years.
- Type I (Gene Therapy): Many achieving motor milestones, survival dramatically improved.
- Type II: Survive to adulthood with respiratory support.
- Type III/IV: Normal or near-normal lifespan.
- Scoliosis Surgery: Improves sitting balance, quality of life, may improve respiratory function.
Evidence Base
- Onasemnogene (gene therapy) trial
- Dramatic improvement in survival and motor function
- Best outcomes with early treatment
- Nusinersen in infantile-onset SMA
- Improved motor function and survival
- Intrathecal administration effective
- Natural history of SMA
- SMN2 copy number correlates with severity
- Baseline for new therapies
- Scoliosis in SMA Type II
- 100% develop scoliosis
- Posterior spinal fusion improves sitting
- Perioperative complications in neuromuscular scoliosis
- High complication rate in SMA
- Experienced team essential
Viva Scenarios
Practice these scenarios to excel in your viva examination
The Infant with SMA Type I and Scoliosis
"8-month-old with confirmed SMA Type I. Has received gene therapy. Now developing thoracolumbar scoliosis of 30 degrees."
This child has benefited from gene therapy but is still at risk for orthopaedic complications. At 30 degrees, I would observe closely. Bracing (TLSO) can be considered for positioning but is unlikely to prevent progression. Given the young age, if the curve progresses rapidly, **growing rod constructs (e.g., MAGEC)** may be considered to allow continued growth. However, any surgery has high perioperative risk. Close collaboration with neurology and respiratory teams is essential. I would monitor closely with serial X-rays every 4-6 months.
The Adolescent with SMA Type II and Severe Scoliosis
"14-year-old with SMA Type II. Wheelchair-dependent. Thoracolumbar scoliosis of 80 degrees with pelvic obliquity. FVC 35%."
This is a challenging case. The scoliosis is severe and the pulmonary function is significantly impaired. However, surgery may still be beneficial. I would assess sitting balance and quality of life. Preoperative optimization with the respiratory team (BiPAP optimization, cough assist) is critical. Surgery: **Posterior spinal fusion from T2 to pelvis** with pelvic fixation (S2-alar-iliac or iliac screws). Expect prolonged ICU stay and potential need for postoperative ventilation. The goal is improved sitting balance and halting curve progression. I would ensure informed consent reflects the high perioperative risk.
Hip Dysplasia in SMA
"Same patient also has bilateral hip subluxation on X-ray. Is this an indication for surgery?"
In SMA, **hip dysplasia is common but surgery is rarely indicated**. The hips are often asymptomatic even when subluxated. Surgery (reconstruction) has high failure rates in this population and the functional gains are minimal since the patient is not walking. I would observe and manage with seating adaptations if there is discomfort. Pain is rare but if present, salvage options like proximal femoral resection may be considered. I would not pursue reconstructive surgery.
MCQ Practice Points
Genetics MCQ
Q: What gene is mutated in SMA? A: SMN1 (Survival Motor Neuron 1) on chromosome 5q.
Classification MCQ
Q: A child who can sit but never walks has which SMA type? A: Type II.
Prognosis MCQ
Q: What correlates with disease severity? A: SMN2 copy number - more copies = milder phenotype.
Treatment MCQ
Q: What is the mechanism of nusinersen (Spinraza)? A: Antisense oligonucleotide that increases SMN2 expression.
Scoliosis Surgery
Q: What is the extent of fusion in SMA scoliosis surgery? A: T2 to pelvis with pelvic fixation (S2-alar-iliac or iliac screws).
Hip Management
Q: How should hip dysplasia in SMA be managed? A: Observation - surgery rarely indicated due to high failure rate and minimal functional benefit.
Australian Context
- Newborn Screening: SMA is now included in newborn screening in some Australian states.
- PBS Access: Gene therapy (Zolgensma) and nusinersen (Spinraza) are PBS-listed with criteria.
- Multidisciplinary Care: Managed in specialized neuromuscular clinics (e.g., Royal Children's Hospital, Westmead).
- Scoliosis Surgery: Performed at tertiary pediatric spine centers.
SPINAL MUSCULAR ATROPHY
High-Yield Exam Summary
GENETICS
- •SMN1 Mutation
- •Autosomal Recessive
- •SMN2 Copies = Prognosis
- •Chromosome 5q
TYPES
- •I: Never sits
- •II: Sits, never walks
- •III: Walks
- •IV: Adult onset
ORTHO ISSUES
- •Scoliosis (universal)
- •Hip Dysplasia
- •Contractures
- •Pelvic Obliquity
SCOLIOSIS SURGERY
- •T2 to Pelvis Fusion
- •Pelvic Fixation Essential
- •High Perioperative Risk
- •ICU Postop Care
MEDICAL THERAPY
- •Onasemnogene (Gene Therapy)
- •Nusinersen (Intrathecal)
- •Risdiplam (Oral)
- •Early Treatment Best
EXAM PEARLS
- •Tongue Fasciculations
- •100% Scoliosis in Type I/II
- •Hip Surgery Rarely Indicated
- •FVC Monitoring Critical
Self-Assessment Quiz
Differential Diagnosis
Similar Neuromuscular Conditions:
- Duchenne Muscular Dystrophy: X-linked, CK elevated, dystrophin gene mutation.
- Congenital Myopathies: Various types, muscle biopsy diagnostic.
- Spinal Cord Lesions: MRI differentiates.
- Metabolic Myopathies: Specific enzyme deficiencies.
Key Differentiators for SMA:
- Genetic testing (SMN1 mutation) is confirmatory.
- Tongue fasciculations are characteristic.
- Normal CK (or mildly elevated).
- Reflexes absent/diminished.