Achondroplasia
FGFR3 Mutation and Short Stature
Key Orthopaedic Issues
Critical Must-Knows
- FGFR3: Gain-of-function mutation.
- Foramen Magnum: Stenosis can cause sudden death in infancy.
- Spinal Stenosis: Symptomatic in 20-30% of adults.
- Genu Varum: Common, may need correction.
- Thoracolumbar Kyphosis: Resolves in most.
Examiner's Pearls
- "FGFR3 gain-of-function
- "Foramen magnum stenosis in infancy
- "Spinal stenosis in adults
- "Rhizomelic shortening
Clinical Imaging
Imaging Gallery
Critical Infant Warning
Sudden Death Risk
Foramen Magnum Stenosis causes cervicomedullary compression. Can lead to central apnea and sudden infant death. Mortality is significantly higher in infancy.
Screening Protocol
Mandatory Screening: Monitor for apnea, hypotonia, feeding issues. MRI Craniocervical Junction at birth/neonatal period is essential.
Achondroplasia Features
| Feature | Description | Management |
|---|---|---|
| Infancy - apnea, sudden death | MRI, decompression if symptomatic | |
| Adults - claudication, neurological | Wide laminectomy | |
| Bowed legs | Osteotomy if symptomatic | |
| Infancy - usually resolves | Most observation |
Achondroplasia Features
Memory Hook:FFRS - FGFR3, Foramen, Rhizomelic, Stenosis.
Clinical Appearance
Memory Hook:MFTL - Macro, Frontal, Trident, Lordosis.
Spinal Issues by Age
Memory Hook:ICA - Infancy (foramen), Childhood (kyphosis), Adult (lumbar).
WIDESurgical Decompression
Memory Hook:Go WIDE or go home - inadequate decompression is the main surgical pitfall!
Overview/Epidemiology
Achondroplasia is the most common skeletal dysplasia.
- Genetics: Autosomal dominant. FGFR3 (Fibroblast Growth Factor Receptor 3) mutation.
- Incidence: 1 in 20,000.
- New Mutations: 80% are new mutations (unaffected parents).
- Pathophysiology: FGFR3 is a negative regulator of bone growth. Gain-of-function mutation → reduced endochondral ossification.
Pathophysiology and Mechanisms
Endochondral Ossification Defect
- FGFR3 normally inhibits bone growth at the growth plate.
- Gain-of-function → excessive inhibition → short bones.
- Affects endochondral bones (limbs, skull base) more than intramembranous.
Why Spinal Stenosis Occurs
- Short pedicles → narrow spinal canal.
- Progressive symptoms in adulthood.
Classification Systems
Clinical Features
- Short Stature: Adult height 120-130cm.
- Rhizomelic Shortening: Proximal limbs (humeri, femora) shorter than distal.
- Macrocephaly: Large head with frontal bossing.
- Midface Hypoplasia: Flat nasal bridge.
- Trident Hands: Short fingers, can't approximate in extension.
- Lumbar Lordosis: Hyperlordosis.
Clinical Assessment
History:
- Developmental milestones.
- Apnea, breathing issues (foramen magnum).
- Back pain, leg pain, claudication (stenosis).
- Leg deformity concerns.
Physical Exam:
- General: Short stature, rhizomelic limbs.
- Head: Macrocephaly, frontal bossing, midface hypoplasia.
- Spine: Lordosis, kyphosis assessment.
- Legs: Genu varum, mechanical axis.
- Neurological: Lower limb reflexes, power (stenosis symptoms).
Investigations
Imaging:
- MRI Craniocervical Junction: At birth/infancy for foramen magnum.
- Spine X-ray: Stenosis assessment.
- MRI Lumbar Spine: If symptomatic.
- Lower Limb X-rays: Mechanical axis.
Genetic:
- FGFR3 mutation testing (usually clinical diagnosis).
Management Algorithm
Foramen Magnum Stenosis
- Screening: MRI of craniocervical junction at birth.
- Symptomatic (apnea, neurological): Neurosurgical decompression.
- Asymptomatic with severe stenosis: Consider prophylactic decompression.
Surgical Techniques
Wide Laminectomy
Indications: Symptomatic spinal stenosis.
Technique: Wide decompression - need to go lateral to pedicles. Multi-level often needed. Avoid fusion if possible to preserve motion.
Considerations: Short pedicles make surgery challenging.
Complications
Neurological Complications
| Complication | Incidence | Risk Factors | Management |
|---|---|---|---|
| Foramen Magnum Stenosis | 5-10% symptomatic | Small foramen magnum | MRI screening, early decompression |
| Sudden Infant Death | 2-5% | Severe stenosis, sleep apnoea | Polysomnography, decompression |
| Myelopathy | Variable | Progressive compression | Cervical or thoracolumbar decompression |
| Cauda Equina Syndrome | Rare | Acute disc herniation | Emergency decompression |
| Radiculopathy | 20-30% adults | Lateral recess stenosis | Conservative or surgical decompression |
Orthopaedic Complications
| Complication | Prevalence | Prevention | Treatment |
|---|---|---|---|
| Progressive Genu Varum | 30-40% | Monitor with growth | Guided growth or osteotomy |
| Thoracolumbar Kyphosis | 90% infants | Avoid early sitting | Bracing, surgery if progressive |
| Hip Flexion Contracture | Common | Physiotherapy | Stretching, rarely surgical release |
| Recurrent Stenosis | 10-20% | Wide decompression | Revision surgery |
Anaesthetic and Perioperative Risks
Critical considerations for surgery in achondroplasia:
- Difficult Airway: Short neck, large head, narrow nasopharynx. Plan for difficult intubation.
- Atlantoaxial Instability: Screen with flexion-extension radiographs. Avoid neck hyperextension.
- Restrictive Lung Disease: Small thorax. Optimise respiratory function preoperatively.
- Spinal Anaesthesia: Technically difficult due to narrow canal. Consider GA instead.
- Positioning: Careful positioning to avoid pressure points and cervical injury.
Postoperative Care
Spinal Decompression Rehabilitation
- Day 1-2: Pain control, mobilisation with supervision
- Week 1-2: Walking program, stair climbing
- Week 2-6: Core strengthening, avoid heavy lifting
- Week 6+: Progressive return to activities
Lower Limb Osteotomy Recovery
- Weight Bearing: Protected weight bearing for 6-8 weeks
- Physiotherapy: Range of motion, strengthening as tolerated
- Hardware Removal: Consider after union confirmed (6-12 months)
- Long-term: Monitor for recurrence during remaining growth
Monitoring and Follow-up
- Neurological: Annual neurological examination
- Spinal: Regular MRI surveillance for stenosis progression
- Lower Limb: Monitor alignment during growth spurts
- Growth: Height velocity charts, orthopaedic review every 6-12 months
Outcomes/Prognosis
Overall Outcomes
- Life Expectancy: Near-normal with appropriate surveillance and intervention
- Functional Independence: Most patients lead independent productive lives
- Cognitive Function: Normal intelligence, no cognitive impairment
Surgical Outcomes
| Procedure | Success Rate | Complications | Long-term Result |
|---|---|---|---|
| Foramen Magnum Decompression | 90% symptom relief | CSF leak 5%, infection 2% | Excellent if done early |
| Lumbar Decompression | 80% improvement | Dural tear 5%, recurrence 15% | Good to excellent |
| Tibial Osteotomy | 85% alignment correction | Delayed union 10% | Generally durable |
| Limb Lengthening | 10-15cm gain possible | Pin site infection 30%, nerve injury 5% | Improves function |
Quality of Life Considerations
- Physical Function: May have limitations but adapt well
- Social Integration: Generally good with supportive environment
- Employment: Wide range of careers possible
- Psychological: Higher rates of depression - screen and support
Evidence Base
- AAP guidelines for achondroplasia
- Foramen magnum screening
- Multidisciplinary care
- Natural history of achondroplasia
- Spinal stenosis in adults
- Foramen magnum in infancy
- Lumbar stenosis surgery outcomes
- Wide decompression needed
- Good symptom relief
- Vosoritide (C-natriuretic peptide analog)
- Increases growth velocity
- New targeted therapy
- Health supervision guidelines
- Developmental screening
- Anticipatory guidance for achondroplasia
Viva Scenarios
Practice these scenarios to excel in your viva examination
Infant with Achondroplasia
"Newborn diagnosed with achondroplasia. What screening do you recommend?"
This infant needs **foramen magnum assessment** because stenosis at the craniocervical junction can cause apnea and sudden death. I would order an **MRI of the craniocervical junction** at birth or early infancy. If significant stenosis is present or the infant has symptoms (apnea, hypotonia, poor feeding), neurosurgical decompression is needed. I would also monitor for **thoracolumbar kyphosis** (common but usually resolves) and avoid unsupported sitting until spine matures.
Adult with Back Pain
"35-year-old with achondroplasia. Presents with neurogenic claudication, bilateral leg weakness."
This patient has **lumbar spinal stenosis**, which is very common in achondroplasia. The short pedicles lead to a narrow canal. Management: **MRI lumbar spine** to confirm. If significant stenosis with neurological symptoms, surgery is indicated. I would perform **wide laminectomy** - decompression must extend lateral to the pedicles. Multi-level decompression is often needed. Avoid fusion if possible.
Genu Varum
"10-year-old with achondroplasia has progressive genu varum. How do you manage?"
Genu varum is common in achondroplasia. If **symptomatic** (pain, instability) or **progressive**, I would offer **corrective osteotomy**. This typically involves a **proximal tibial osteotomy** and possibly distal femoral osteotomy to correct mechanical axis. I would discuss with the family if they are interested in **limb lengthening** (can be combined) but counsel about high complication rates and lengthy treatment.
MCQ Practice Points
Genetics MCQ
Q: What gene is mutated in achondroplasia? A: FGFR3 (gain-of-function mutation).
Stenosis MCQ
Q: What is the major orthopaedic issue in adults? A: Lumbar spinal stenosis.
Infant MCQ
Q: What is the dangerous issue in infancy? A: Foramen magnum stenosis (can cause sudden death).
Limbs MCQ
Q: What is the pattern of limb shortening? A: Rhizomelic (proximal limbs shorter than distal).
Surgery Pearl
Q: What is key to successful lumbar decompression in achondroplasia? A: Wide decompression extending lateral to the pedicles. Multi-level often needed. Short pedicles cause narrow canal.
New Therapy Pearl
Q: What new medical therapy is available for achondroplasia? A: Vosoritide - a C-natriuretic peptide analog that increases growth velocity by counteracting FGFR3.
Australian Context
- Screening: MRI at birth/infancy for foramen magnum.
- Genetic Counseling: Important for family planning.
- Little People of Australia: Support group.
- New Therapies: Vosoritide (TGA approval pending).
ACHONDROPLASIA
High-Yield Exam Summary
GENETICS
- •FGFR3 Mutation
- •Gain-of-function
- •Autosomal Dominant
- •80% new mutations
CLINICAL
- •Rhizomelic short stature
- •Macrocephaly
- •Trident hands
- •Lumbar lordosis
SPINE
- •Foramen magnum (infant)
- •Lumbar stenosis (adult)
- •Thoracolumbar kyphosis
- •Short pedicles
LIMBS
- •Genu varum
- •Osteotomy if symptomatic
- •Limb lengthening (controversial)
- •High complication rate
FORAMEN MAGNUM
- •Screen at birth (MRI)
- •Apnea, sudden death risk
- •Decompression if symptomatic
- •Neurosurgery referral
NEW THERAPIES
- •Vosoritide
- •C-natriuretic peptide analog
- •Increases growth velocity
- •TGA approval pending
Self-Assessment Quiz
Differential Diagnosis
Skeletal Dysplasias:
| Condition | Gene | Key Differentiator |
|---|---|---|
| Achondroplasia | FGFR3 | Most common, rhizomelic, foramen magnum |
| Hypochondroplasia | FGFR3 | Milder form, less obvious features |
| Thanatophoric Dysplasia | FGFR3 | Lethal, very short limbs |
| Pseudoachondroplasia | COMP | Normal face, short trunk + limbs |
| Spondyloepiphyseal Dysplasia | COL2A1 | Short trunk, normal face |
| Diastrophic Dysplasia | SLC26A2 | Hitchhiker thumb, cauliflower ear |
Key Distinguishing Points:
- Achondroplasia: Characteristic face (frontal bossing, midface hypoplasia)
- Pseudoachondroplasia: Normal face (distinguishes from achondroplasia)
- Thanatophoric: Lethal, telephone receiver femur
- Diastrophic: Hitchhiker thumb is pathognomonic