High Yield Overview

SKELETAL DYSPLASIAS

Over 400 Genetic Bone Disorders | Pattern Recognition | Radiographic Diagnosis

1:5000Collective incidence of skeletal dysplasias

400+Recognized skeletal dysplasia types

1:25000Achondroplasia - most common viable dysplasia

1:15000Osteogenesis imperfecta incidence

RADIOGRAPHIC CLASSIFICATION

Osteopenic

PatternDecreased bone density (OI, hypophosphatasia)

TreatmentBisphosphonates, fracture prevention

Sclerosing

PatternIncreased bone density (osteopetrosis, pyknodysostosis)

TreatmentBMT for severe osteopetrosis

Short-limbed

PatternRhizomelic/mesomelic/acromelic (achondroplasia)

TreatmentLimb lengthening, spinal surgery

Short-trunk

PatternVertebral involvement (SED, Morquio)

TreatmentSpinal stabilization, ERT for MPS

Critical Must-Knows

Achondroplasia - FGFR3 mutation, rhizomelic shortening, champagne-glass pelvis, spinal stenosis
Osteogenesis imperfecta - collagen type I defect, blue sclerae, fractures, bisphosphonate treatment
Pattern recognition - look at bone density (decreased/increased) and shape (epiphyseal/metaphyseal/diaphyseal)
Spinal complications - cervical instability, kyphosis, stenosis are major surgical considerations
New treatments - vosoritide for achondroplasia, bisphosphonates for OI, enzyme replacement for MPS

Examiner's Pearls

"
Achondroplasia: FGFR3 mutation, autosomal dominant, normal intelligence, spinal stenosis risk
"
OI Type I: blue sclerae, hearing loss - Type II is lethal
"
Mucopolysaccharidoses show dysostosis multiplex on X-ray
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Osteopetrosis: dense but brittle bones - osteoclast dysfunction

Clinical Imaging

Imaging Gallery

Comparative Mouse Radiographs. Comparative radiographs of cn/+ and cn/cn mice at 5 weeks from the same litter are shown. Pairs of mice were radiographed together for size comparison. a: Entire skeleto — Comparative Mouse Radiographs. Comparative radiographs of cn/+ and cn/cn mice at 5 weeks from the same litter are shown. Pairs of mice were radiographCredit: Shapiro F et al. via BMC Musculoskelet Disord via Open-i (NIH) (Open Access (CC BY))

Clinical features.(a) Clinical features include hypertelorism, malar flattening, downslanting palpebral fissures (3-II-2/3/4, 3-III-1/2 and 4-II-1), proptosis (3-III-1/2), joint hypermobility (4-II-1) — Clinical features.(a) Clinical features include hypertelorism, malar flattening, downslanting palpebral fissures (3-II-2/3/4, 3-III-1/2 and 4-II-1), pCredit: Open-i / NIH via Open-i (NIH) (Open Access (CC BY))

Radiographs of case 4 (A) and case 5 (B) show generalized undermineralization, short-limb dwarfism, rhizomelic limb shortening, small chest, and platyspondyly. Periosteal new bone in multiple healing — Radiographs of case 4 (A) and case 5 (B) show generalized undermineralization, short-limb dwarfism, rhizomelic limb shortening, small chest, and platyCredit: Open-i / NIH via Open-i (NIH) (Open Access (CC BY))

Skeletal defects associated with SHOX deficiency. A, Madelung deformity in a patient with LWD. The 19-year-old female with a 46,XX karyotype harbors a paternally inherited heterozygous microdeletion i — Skeletal defects associated with SHOX deficiency. A, Madelung deformity in a patient with LWD. The 19-year-old female with a 46,XX karyotype harbors aCredit: Marchini A et al. via Endocr. Rev. via Open-i (NIH) (Open Access (CC BY))

Critical Skeletal Dysplasia Exam Points

Achondroplasia

FGFR3 mutation causing decreased endochondral ossification. Rhizomelic shortening (proximal limbs), champagne-glass pelvis, frontal bossing, trident hand. Major orthopaedic issues: foramen magnum stenosis, spinal stenosis, genu varum.

Osteogenesis Imperfecta

Collagen type I defect (COL1A1/COL1A2). Blue sclerae, fragile bones, hearing loss. Type I (mild, blue sclerae) to Type II (lethal). Treatment: bisphosphonates, rodding procedures. Beware NAI misdiagnosis.

Mucopolysaccharidoses

Lysosomal storage disorders - enzyme deficiency leads to GAG accumulation. Dysostosis multiplex on X-ray. Hurler (MPS I) most severe, Morquio (MPS IV) has unique skeletal features. Enzyme replacement available for some.

Sclerosing Dysplasias

Osteopetrosis - osteoclast dysfunction causing dense but brittle bones. Erlenmeyer flask deformity, sandwich vertebrae. Severe form needs BMT. Pyknodysostosis - dense bones + acroosteolysis (Toulouse-Lautrec had this).

At a Glance

Skeletal dysplasias encompass 400+ genetic bone disorders (collective incidence ~1:5,000) classified by radiographic pattern: osteopenic (OI), sclerosing (osteopetrosis), short-limbed (achondroplasia), or short-trunk (SED, Morquio). Achondroplasia (most common viable dysplasia, 1:25,000) results from FGFR3 gain-of-function mutation causing rhizomelic shortening, champagne-glass pelvis, trident hand, and progressive spinal stenosis. Osteogenesis imperfecta (COL1A1/COL1A2 collagen type I defects) presents with blue sclerae, fractures, hearing loss, and dentinogenesis imperfecta—treated with bisphosphonates and rodding procedures. Mucopolysaccharidoses (lysosomal storage disorders) show dysostosis multiplex on X-ray (J-shaped sella, hook vertebrae, paddle ribs). Spinal complications (cervical instability, stenosis, kyphosis) are major surgical considerations across dysplasia types. Newer treatments include vosoritide for achondroplasia and enzyme replacement for MPS.

Mnemonic

Achondroplasia Features - STAMP

Spinal stenosis

Narrow canal, short pedicles - major long-term issue

Trident hand

Persistent space between 3rd and 4th fingers

Autosomal dominant, FGFR3

Gain-of-function mutation, 80% new mutations

Macrocephaly and frontal bossing

Large head, prominent forehead, midface hypoplasia

Pelvis champagne-glass

Horizontal acetabular roofs, narrow sacrosciatic notch

Memory Hook:STAMP the diagnosis - achondroplasia leaves its STAMP on the skeleton

Mnemonic

Osteogenesis Imperfecta Features - BONED

Blue sclerae

Thin sclerae show underlying choroidal vessels

Osteopenia and fractures

Multiple fractures, especially long bones

Normal intelligence

Cognition unaffected, distinguish from NAI

Ear - hearing loss

Conductive then sensorineural (otosclerosis)

Dentinogenesis imperfecta

Opalescent teeth, Type I collagen in dentin

Memory Hook:BONED - brittle bones need this easy mnemonic

Mnemonic

Dysostosis Multiplex Features - JDHIP

J-shaped sella

Anterior extension of sella turcica

Diaphyseal widening

Expanded medullary canals in long bones

Hook vertebrae

Anteroinferior beaking of vertebral bodies

Inferior beaking of L1/L2

Hypoplastic vertebra at thoracolumbar junction

Paddle ribs

Widened, oar-shaped ribs

Memory Hook:JDHIP - J-shaped sella, Dysostosis, Hook vertebrae = MPS storage diseases

Overview and Epidemiology

Skeletal dysplasias are a heterogeneous group of over 400 genetic disorders affecting bone and cartilage development. While individually rare, they collectively represent a significant burden of genetic skeletal disease with an overall incidence of approximately 1 in 5000 live births. [1,2]

Nosology and Classification: The Nosology and Classification of Genetic Skeletal Disorders (revised periodically by the International Skeletal Dysplasia Society) currently recognizes 461 different conditions organized into 42 groups based on clinical, radiographic, and molecular criteria.

Major Categories by Affected Structure:

Disorders of cartilage growth (achondroplasia group)
Disorders of collagen synthesis (osteogenesis imperfecta)
Lysosomal storage disorders (mucopolysaccharidoses)
Disorders of mineral homeostasis (rickets, hypophosphatasia)
Disorders of bone resorption (osteopetrosis)

Pattern Recognition

Radiographic diagnosis of skeletal dysplasias primarily relies on pattern recognition. Key features to assess: (1) Bone density - decreased (osteopenic) or increased (sclerosing); (2) Which part of the bone is affected - epiphyseal, metaphyseal, or diaphyseal; (3) Limb proportions - rhizomelic (proximal), mesomelic (middle), or acromelic (distal); (4) Spine involvement - platyspondyly, vertebral beaking.

Common Viable Skeletal Dysplasias:

Achondroplasia (1:25,000) - most common
Osteogenesis imperfecta (1:15,000)
Spondyloepiphyseal dysplasia (1:100,000)
Multiple epiphyseal dysplasia (1:100,000)
Cleidocranial dysplasia (1:1,000,000)

Pathophysiology

Molecular Basis

Skeletal dysplasias result from mutations affecting various pathways:

Molecular Pathways in Skeletal Dysplasias

Pathway/Gene	Dysplasia	Effect
FGFR3	Achondroplasia, thanatophoric dysplasia	Gain-of-function inhibits chondrocyte proliferation
COL1A1/COL1A2	Osteogenesis imperfecta	Abnormal type I collagen synthesis
COL2A1	SED congenita, Stickler syndrome	Abnormal type II collagen in cartilage
Lysosomal enzymes	Mucopolysaccharidoses	GAG accumulation in tissues
TCIRG1/CLCN7	Osteopetrosis	Osteoclast dysfunction - no resorption
RUNX2	Cleidocranial dysplasia	Defective intramembranous ossification

Bone Formation Affected

Endochondral Ossification Disorders:

Achondroplasia group - growth plate dysfunction
Epiphyseal dysplasias - cartilage model affected
Most short-limbed dwarfism

Intramembranous Ossification Disorders:

Cleidocranial dysplasia - clavicle, skull
Affects flat bones

Combined Disorders:

Osteogenesis imperfecta - affects all type I collagen-containing tissues
Osteopetrosis - affects bone remodeling throughout skeleton

Classification

Radiographic Classification Approach

Osteopenic Dysplasias (Decreased Density):

Osteogenesis imperfecta - fragile bones, multiple fractures
Hypophosphatasia - rickets-like changes, deficient alkaline phosphatase
Idiopathic juvenile osteoporosis

Sclerosing Dysplasias (Increased Density):

Osteopetrosis - diffuse sclerosis, Erlenmeyer flask
Pyknodysostosis - sclerosis + acroosteolysis
Osteopoikilosis - spotty sclerosis (benign)
Melorheostosis - flowing candle wax appearance

Density assessment on radiograph is the first step in classifying an unknown skeletal dysplasia. This immediately narrows the differential diagnosis.

Clinical Presentation

Skeletal dysplasias present with characteristic clinical features that guide initial diagnosis:

General Presentation Patterns

Short Stature:

Proportionate vs disproportionate (most skeletal dysplasias)
Short limb vs short trunk patterns
Measure arm span, sitting height, upper/lower segment ratio

Disproportionate Short Stature Patterns:

Rhizomelic: Proximal segment shortened (achondroplasia)
Mesomelic: Middle segment shortened (Langer mesomelic)
Acromelic: Distal segment shortened (acromicric dysplasia)
Short trunk: Spine predominantly affected (SED, Morquio)

Specific Clinical Signs

Key Clinical Signs by Dysplasia

Sign	Dysplasia	Significance
Blue sclerae	Osteogenesis imperfecta Type I	Thin sclerae showing choroid vessels
Frontal bossing	Achondroplasia	Large head with prominent forehead
Trident hand	Achondroplasia	Gap between 3rd and 4th fingers
Approximate shoulders	Cleidocranial dysplasia	Absent/hypoplastic clavicles
Coarse facies	MPS (Hurler, Hunter)	GAG accumulation in soft tissues
Corneal clouding	MPS I (Hurler/Scheie)	NOT in Hunter syndrome

History Taking

Family History:

Pattern of inheritance (AD, AR, X-linked)
80% of achondroplasia cases are new mutations
Parental age (increased paternal age associated with new dominant mutations)

Developmental History:

Motor milestones - often delayed in severe forms
Cognitive development - normal in most (except MPS types I-III)
Growth velocity and pattern

Associated Symptoms:

Respiratory issues (thoracic involvement, obstructive sleep apnoea)
Hearing loss (OI, MPS)
Visual problems (corneal clouding in MPS)
Joint pain/stiffness

Investigations

Radiographic Assessment

The skeletal survey is the cornerstone of diagnosis in skeletal dysplasias:

Standard Skeletal Survey:

Skull (AP, lateral)
Spine (AP, lateral)
Chest (AP)
Pelvis (AP)
Long bones (humerus, radius/ulna, femur, tibia/fibula)
Hand (AP)

Systematic Radiographic Evaluation:

Bone Density Assessment
- Decreased: OI, hypophosphatasia
- Increased: osteopetrosis, pyknodysostosis
Location of Involvement
- Epiphyseal: MED, SED, chondrodysplasia punctata
- Metaphyseal: achondroplasia, rickets, metaphyseal chondrodysplasia
- Diaphyseal: progressive diaphyseal dysplasia, melorheostosis
Limb Proportions
- Measure humerus and femur lengths
- Calculate rhizomelic ratio
Spine Evaluation
- Vertebral height and shape
- Interpedicular distance
- Platyspondyly, beaking, stenosis

Genetic Testing

Indications:

Confirm clinical/radiographic diagnosis
Genetic counselling
Prenatal diagnosis in subsequent pregnancies
Access to specific treatments

Methods:

Single gene testing (when diagnosis clear)
Skeletal dysplasia gene panels (50-500 genes)
Exome/genome sequencing (atypical presentations)

Laboratory Tests

Osteogenesis Imperfecta:

Bone markers, vitamin D, calcium
Collagen analysis (skin biopsy, historical)
Genetic testing (COL1A1/COL1A2)

Mucopolysaccharidoses:

Urine GAG screening (dermatan sulfate, heparan sulfate)
Enzyme assay in leukocytes (specific enzyme for each MPS type)
Genetic confirmation

Metabolic Bone Disease:

Alkaline phosphatase (low in hypophosphatasia)
Calcium, phosphate, vitamin D
PTH levels

Additional Imaging

MRI:

Foramen magnum stenosis assessment (achondroplasia)
Spinal stenosis evaluation
Cervical cord compression
Brain MRI if developmental concerns

CT:

3D reconstruction for surgical planning
Cervical spine assessment

Echocardiography:

Cardiac involvement in MPS
Aortic root in Marfan syndrome (connective tissue, not dysplasia)

Achondroplasia

Achondroplasia is the most common viable skeletal dysplasia, caused by gain-of-function mutations in the FGFR3 gene. [3,4]

Genetics and Pathophysiology

Gene: FGFR3 (fibroblast growth factor receptor 3) on chromosome 4p16.3
Mutation: G380R (glycine to arginine) in 97% of cases
Inheritance: Autosomal dominant, but 80% are new mutations
Mechanism: Constitutive activation of FGFR3 inhibits chondrocyte proliferation in growth plates

FGFR3 Mutation Spectrum

FGFR3 mutations cause a spectrum of severity: Thanatophoric dysplasia (most severe, lethal) through SADDAN syndrome to Achondroplasia to Hypochondroplasia (mildest). All are gain-of-function mutations with varying degrees of receptor activation.

Clinical Features

Craniofacial:

Macrocephaly with frontal bossing
Midface hypoplasia
Depressed nasal bridge
Normal intelligence

Skeletal:

Rhizomelic shortening (proximal limbs most affected)
Trident hand configuration
Genu varum (tibial bowing)
Thoracolumbar kyphosis (in infancy)
Exaggerated lumbar lordosis (develops later)

Radiographic Features

Radiographic Features of Achondroplasia

Region	Finding	Clinical Significance
Skull	Enlarged calvarium, small skull base, foramen magnum stenosis	Risk of cervicomedullary compression
Spine	Narrow interpedicular distance caudally, short pedicles, small canal	Spinal stenosis - major cause of morbidity
Pelvis	Champagne-glass shape, horizontal acetabular roofs, narrow sciatic notch	Characteristic diagnostic feature
Long bones	Rhizomelic shortening, metaphyseal flaring, chevron deformity of femur	Affects endochondral ossification
Hand	Trident configuration, short tubular bones	Persistent gap between 3rd and 4th fingers

Orthopaedic Management

Spinal Issues:

Foramen magnum stenosis - monitor in infancy, decompression if symptomatic
Thoracolumbar kyphosis - bracing, fusion if progressive
Spinal stenosis - develops in adults, may need multilevel decompression

Lower Limb:

Genu varum - guided growth or osteotomy
Limb lengthening - controversial, significant complications
Avoid obesity to reduce mechanical stress

New Treatments:

Vosoritide (C-natriuretic peptide analogue) - FDA approved 2021
Works by antagonizing FGFR3 signaling
Shown to increase growth velocity in clinical trials

Osteogenesis Imperfecta

Osteogenesis imperfecta (OI) is a group of genetic disorders affecting type I collagen, resulting in bone fragility and other connective tissue manifestations. [5,6]

Genetics

Genes: Primarily COL1A1 and COL1A2 (encode type I collagen)
Inheritance: Mostly autosomal dominant (Types I-IV)
Newer genes: CRTAP, LEPRE1, PPIB (recessive forms)

Sillence Classification

Sillence Classification of Osteogenesis Imperfecta

Type	Severity	Sclerae	Key Features
Type I	Mild	Blue	Fractures after walking, normal stature, hearing loss common
Type II	Lethal	Dark blue	Multiple intrauterine fractures, beaded ribs, perinatal death
Type III	Severe	Variable	Progressive deformity, short stature, wheelchair by teens
Type IV	Moderate	White/blue	Moderate fragility, normal sclerae in adults, dentinogenesis imperfecta

Clinical Features

Classic Triad:

Blue sclerae (thin sclerae showing choroidal vessels)
Bone fragility (multiple fractures)
Hearing loss (conductive then sensorineural)

Other Features:

Dentinogenesis imperfecta (opalescent teeth)
Joint hypermobility
Easy bruising
Short stature (severe forms)
Basilar invagination (Type III)

NAI Misdiagnosis

OI can be mistaken for non-accidental injury (NAI) due to multiple unexplained fractures. Key differentiators: blue sclerae, family history, Wormian bones on skull X-ray, osteopenia, and genetic testing. Always consider OI before diagnosing NAI in an infant with fractures.

Radiographic Features

Generalized osteopenia
Multiple fractures at various stages of healing
Wormian bones (multiple small bones in skull sutures)
Codfish vertebrae (biconcave)
Gracile long bones
Popcorn calcification in epiphyses (severe forms)

Management

Medical:

Bisphosphonates (pamidronate, zoledronic acid) - increase BMD, reduce fractures
Calcium and vitamin D supplementation
Physical therapy - strengthen muscles, prevent falls

Surgical:

Intramedullary rodding - stabilize long bones, prevent deformity
Telescoping rods (Bailey-Dubow, Fassier-Duval) - grow with child
Spinal fusion for scoliosis
Basilar impression decompression if needed

Rodding Principles

Intramedullary rodding in OI uses telescoping designs that elongate with growth. Key principles: rod both femurs and tibias for walking patients, use solid rods for non-ambulatory patients, fixation should span entire bone, and augment with bisphosphonates pre- and post-operatively.

Mucopolysaccharidoses

The mucopolysaccharidoses (MPS) are lysosomal storage disorders caused by deficiency of enzymes that degrade glycosaminoglycans (GAGs). The accumulation of GAGs in tissues causes progressive multisystem disease. [7]

Classification

Mucopolysaccharidoses Types

Type	Name	Enzyme Deficiency	Key Features
MPS I	Hurler/Scheie	Alpha-L-iduronidase	Most severe, cognitive decline, corneal clouding
MPS II	Hunter	Iduronate sulfatase	X-linked, no corneal clouding, variable severity
MPS III	Sanfilippo	Various heparan sulfate enzymes	Behavioral issues, mild skeletal involvement
MPS IV	Morquio	Galactose-6-sulfatase (A) or B-galactosidase (B)	Normal intelligence, severe skeletal involvement, odontoid hypoplasia
MPS VI	Maroteaux-Lamy	Arylsulfatase B	Normal intelligence, severe skeletal involvement

Dysostosis Multiplex

The radiographic constellation of findings in MPS is termed "dysostosis multiplex":

J-shaped sella turcica
Paddle-shaped (oar-shaped) ribs
Hook-shaped vertebrae with anteroinferior beaking
Diaphyseal widening of long bones
Bullet-shaped metacarpals with proximal pointing
Hypoplastic L1/L2 vertebra causing kyphosis

Orthopaedic Considerations

Cervical Spine:

Odontoid hypoplasia (especially Morquio)
Atlantoaxial instability
Cervical stenosis
May need occipitocervical fusion

Thoracolumbar Spine:

Gibbus deformity at thoracolumbar junction
Progressive kyphosis
May need spinal fusion

Lower Limb:

Genu valgum (especially Morquio)
Hip dysplasia
Guided growth or osteotomy

Treatment

Medical:

Enzyme replacement therapy (ERT) - available for MPS I, II, IVA, VI
Hematopoietic stem cell transplant - best if early, for MPS I
Gene therapy - under investigation

Surgical:

Address spinal instability early
Joint procedures as needed
Cardiac valve surgery in some types

Morquio Syndrome

Morquio syndrome (MPS IVA) has unique features: normal intelligence, severe skeletal involvement, odontoid hypoplasia with atlantoaxial instability. These patients need cervical spine precautions for any anaesthesia. Always obtain flexion-extension cervical spine imaging before surgery.

Other Important Dysplasias

Osteopetrosis ("Marble Bone Disease"):

Osteoclast dysfunction - failure of bone resorption
Diffuse sclerosis but paradoxically brittle bones
Erlenmeyer flask deformity (failure of metaphyseal remodeling)
Sandwich vertebrae, bone-within-bone appearance
Severe form: pancytopenia, cranial nerve compression
Treatment: BMT for severe infantile form

Pyknodysostosis:

Cathepsin K deficiency
Dense bones + acroosteolysis (terminal phalangeal resorption)
Open fontanelles, micrognathia
Toulouse-Lautrec reportedly had this condition
Fractures common despite dense appearance

Sclerosing dysplasias paradoxically have fragile bones despite increased radiographic density due to abnormal bone remodeling.

Management

Management of skeletal dysplasias requires a multidisciplinary approach addressing both medical and orthopaedic needs.

Targeted Drug Therapies:

Vosoritide (achondroplasia) - C-natriuretic peptide analogue, FDA approved 2021
Bisphosphonates (OI) - pamidronate, zoledronic acid to increase BMD
Enzyme replacement (MPS) - laronidase (MPS I), idursulfase (MPS II), elosulfase (MPS IVA)
HSCT (MPS I severe) - best outcomes if performed early

Supportive Medical Care:

Growth hormone - not effective in most true skeletal dysplasias
Vitamin D and calcium supplementation
Respiratory support - CPAP for obstructive sleep apnoea
Pain management - multimodal approach

Monitoring:

Regular growth measurements
Sleep studies for at-risk patients
Cardiac echo for MPS patients
Hearing and vision screening

The medical management aims to optimize quality of life and address systemic manifestations.

Surgical Technique

Intramedullary Rodding in OI

Indications:

Recurrent fractures (greater than 2 per year in same bone)
Progressive bowing deformity
Anticipated fracture through osteopenic segment
Femur and tibia most commonly rodded

Principles:

Correct angular deformity with osteotomies if needed
Rod should span entire bone length
Avoid stress risers at rod ends
Combine with bisphosphonate therapy

Rod Types:

Rod Type	Mechanism	Best For	Consideration
Solid rod (Rush, Steinmann)	Fixed length	Non-ambulatory patients	Needs replacement with growth
Bailey-Dubow	Telescopes at metaphysis	Growing children	Complex, can malfunction
Fassier-Duval	Telescopes at diaphysis	Growing children	Newer design, better function

Deformity Correction Osteotomies

Technique:

Multiple osteotomies through apex of deformity
"Shish-kebab" technique - threading fragments on rod
Minimal periosteal stripping to preserve blood supply

Complications

Orthopaedic Complications

Spinal Complications:

Foramen magnum stenosis (achondroplasia) - brainstem compression
Spinal stenosis - progressive neurological deficit
Atlantoaxial instability (MPS, SED) - risk of cord injury
Cervical kyphosis (diastrophic dysplasia) - may need early fusion
Basilar invagination (OI) - cranial settling
Progressive scoliosis - respiratory compromise

Lower Limb Complications:

Angular deformity progression - genu varum/valgum
Premature osteoarthritis (MED, SED)
Pathological fractures (OI, osteopetrosis paradoxically)
Hip dysplasia and dislocation (MPS, congenital dysplasias)
Growth plate injury from recurrent fractures

Joint Complications:

Early-onset degenerative disease
Joint contractures (MPS)
Ligamentous laxity (OI, Ehlers-Danlos overlap)

Medical Complications

Medical Complications by Dysplasia Type

Condition	Complication	Management
Achondroplasia	Obstructive sleep apnoea, obesity	Sleep study, CPAP, weight management
OI	Hearing loss, respiratory failure (severe)	Audiology, pulmonology input
MPS	Cardiac valve disease, cognitive decline	Echo surveillance, HSCT if eligible
Osteopetrosis (severe)	Pancytopenia, blindness, deafness	BMT, supportive care
Thanatophoric dysplasia	Respiratory failure (lethal)	Perinatal palliative care

Surgical Complications

Fracture Fixation in Abnormal Bone:

OI: Implant cutout, refracture at implant ends
Osteopetrosis: Difficult drilling, delayed healing
Solution: Telescoping rods in OI, staged treatment

Spinal Surgery:

Dural ectasia (some syndromes)
Abnormal anatomy
Difficult intubation (short neck, atlantoaxial instability)
Increased bleeding risk

Anaesthetic Considerations

Cervical spine instability: Morquio, SED, Down syndrome - fibreoptic intubation may be needed. Difficult airway: short neck, large tongue, restricted mouth opening (MPS). Always have experienced anaesthesia team for skeletal dysplasia patients.

Postoperative Care

General Postoperative Principles

Immediate Postoperative:

Close neurological monitoring after spinal procedures
Pain management - multimodal approach
Early mobilization when safe
DVT prophylaxis (mechanical, consider chemical in adults)

Fracture/Rodding Postoperative:

Protected weight bearing initially
Serial radiographs to confirm healing
Monitor for implant complications
Resume bisphosphonates when appropriate

Rehabilitation

Procedure	Mobilization	Weight Bearing	Return to Activity
IM rodding femur	Day 1-2	PWB 6 weeks, WBAT 12 weeks	4-6 months
IM rodding tibia	Day 1-2	PWB 6 weeks, WBAT 12 weeks	4-6 months
Cervical fusion	Collar 6-12 weeks	N/A	3-6 months
Spinal decompression	Day 1	Full	6-12 weeks

Outcomes

Outcomes by Condition

Achondroplasia:

Life expectancy near normal with appropriate management
Foramen magnum decompression highly effective when needed
Spinal stenosis surgery improves quality of life
Vosoritide showing promise for improved height outcomes

Osteogenesis Imperfecta:

Bisphosphonates: 30-50% reduction in fracture rate
Rodding: 90%+ reduction in fractures in rodded bones
Quality of life significantly improved with modern management
Type II remains uniformly lethal

Surgical Outcomes Summary

Procedure	Success Rate	Complications	Revision Rate
IM rodding (OI)	85-95%	Rod migration, refracture	20-30% (growth)
Foramen magnum decompression	90%+	CSF leak, infection	5-10%
Cervical fusion (MPS)	80-90%	Nonunion, progression	10-15%
Spinal stenosis decompression	70-80%	Instability, recurrence	15-20%

Evidence Base

Level II

📚 Savarirayan R et al. Vosoritide in children with achondroplasia (2020)

Key Findings:

First targeted therapy for achondroplasia
1.57 cm/year increase in growth velocity
FDA approved 2021 for children 5+ years

Clinical Implication: Vosoritide represents a paradigm shift from symptomatic to disease-modifying treatment in achondroplasia. Long-term outcomes and final height impact still being studied.

Level I

📚 Dwan K et al. Bisphosphonates for osteogenesis imperfecta (Cochrane 2016)

Key Findings:

Bisphosphonates increase BMD in OI
Fracture reduction evidence limited
Benefits must be weighed against long-term unknowns

Clinical Implication: Bisphosphonates are standard of care for moderate-severe OI to increase BMD, though definitive fracture prevention data remains limited.

Level II

📚 Wraith JE et al. Enzyme replacement therapy for MPS I (2004)

Key Findings:

ERT improves soft tissue manifestations
No reversal of skeletal changes
Earlier treatment likely more beneficial

Clinical Implication: ERT in MPS should be started early before irreversible skeletal changes occur. Skeletal surgery still needed for established deformity.

Level III

📚 Cheung MS et al. Osteogenesis imperfecta incidence and outcomes (2007)

Key Findings:

Type I OI most common and mildest
Type II (lethal) underrepresented in live births
Improved survival with modern management

Clinical Implication: Type I OI is most common in clinical practice. Patients benefit from multidisciplinary care including orthopaedics, endocrinology, and genetics.

Exam Viva Scenarios

Practice these scenarios to excel in your viva examination

VIVA SCENARIOStandard

EXAMINER

"Classic presentation of achondroplasia or related FGFR3 disorder. The examiner wants systematic evaluation."

EXCEPTIONAL ANSWER

This presentation suggests achondroplasia or a related short-limbed skeletal dysplasia. Key history includes prenatal diagnosis, family history, developmental milestones, and any neurological symptoms suggesting foramen magnum compression. Examination should assess limb proportions - achondroplasia causes rhizomelic (proximal) shortening, measure arm span to height ratio, look for trident hand, genu varum, and thoracolumbar kyphosis. Radiographic evaluation includes skeletal survey looking for champagne-glass pelvis, narrow spinal canal with decreasing interpedicular distance, and metaphyseal flaring. Genetic testing for FGFR3 mutation confirms diagnosis. I would also assess for foramen magnum stenosis with MRI if any neurological concerns.

KEY POINTS TO SCORE

Achondroplasia - FGFR3 mutation, autosomal dominant

Rhizomelic shortening - measure limb segments

Champagne-glass pelvis on X-ray is pathognomonic

Foramen magnum stenosis needs assessment in infancy

Vosoritide now available as targeted treatment

COMMON TRAPS

✗Forgetting foramen magnum stenosis - can be lethal

✗Not distinguishing from thanatophoric dysplasia (lethal)

✗Missing spinal stenosis risk in adults

VIVA SCENARIOStandard

EXAMINER

"Important scenario - need to distinguish OI from NAI while ensuring child safety."

EXCEPTIONAL ANSWER

This requires careful evaluation to distinguish OI from non-accidental injury while not missing either diagnosis. I would take detailed family history looking for OI features in parents or relatives, and birth history for intrauterine fractures. Clinical examination looks for blue sclerae, dentinogenesis imperfecta, joint hypermobility, and hearing abnormalities. Radiographic findings supporting OI include generalized osteopenia, Wormian bones in skull, gracile bones, and codfish vertebrae. If OI is suspected, genetic testing for COL1A1/COL1A2 mutations should be performed. However, I would involve a multidisciplinary team including paediatricians and child protection services to ensure thorough evaluation of both possibilities. The diagnosis is not mutually exclusive - children with OI can also be abused.

KEY POINTS TO SCORE

Blue sclerae, Wormian bones, osteopenia support OI

Family history crucial - but 35% are new mutations

Genetic testing confirms diagnosis

OI and NAI can coexist - always ensure child safety

MDT approach essential

COMMON TRAPS

✗Assuming OI excludes NAI - both can occur

✗Not involving child protection appropriately

✗Missing Type IV OI which has normal sclerae

VIVA SCENARIOChallenging

EXAMINER

"Tests knowledge of MPS complications and perioperative considerations."

EXCEPTIONAL ANSWER

Morquio syndrome (MPS IVA) has several critical anaesthetic and surgical considerations. The most important is cervical spine instability due to odontoid hypoplasia - I would obtain flexion-extension cervical X-rays and possibly MRI before any surgery. Intubation should be performed with cervical spine precautions. Other concerns include restrictive lung disease from thoracic cage abnormalities, cardiac valve disease requiring echo assessment, and difficult airway due to short neck and GAG deposition. From an orthopaedic perspective, bone quality may be compromised, and wound healing can be affected by connective tissue abnormalities. I would also consider that Morquio patients have normal intelligence and should be appropriately counselled about the procedure.

KEY POINTS TO SCORE

Cervical spine instability - odontoid hypoplasia

Flexion-extension X-rays and MRI before surgery

Cardiac echo - valve disease common

Difficult airway anticipated

Normal intelligence - appropriate consent discussion

COMMON TRAPS

✗Forgetting cervical spine assessment

✗Not checking cardiac status

✗Assuming cognitive impairment (Morquio has normal intelligence)

VIVA SCENARIOStandard

EXAMINER

"Tests systematic approach to pattern recognition in skeletal dysplasias."

EXCEPTIONAL ANSWER

The radiographic approach to skeletal dysplasias follows a systematic pattern recognition method. First, assess bone density - is it decreased (osteopenic dysplasias like OI) or increased (sclerosing dysplasias like osteopetrosis)? Second, identify which part of the bone is affected - epiphyseal (MED, SED), metaphyseal (achondroplasia, rickets), or diaphyseal (progressive diaphyseal dysplasia). Third, assess limb proportions - rhizomelic, mesomelic, or acromelic shortening. Fourth, evaluate the spine for platyspondyly, vertebral beaking, or interpedicular distance abnormalities. Fifth, look for pathognomonic features like champagne-glass pelvis (achondroplasia), Wormian bones (OI, cleidocranial), or dysostosis multiplex (MPS). The combination of these features usually narrows the differential significantly, and genetic testing confirms the diagnosis.

KEY POINTS TO SCORE

Bone density first - osteopenic vs sclerosing

Location - epiphyseal, metaphyseal, or diaphyseal

Limb proportions - rhizomelic, mesomelic, acromelic

Spine involvement - platyspondyly, beaking

Pathognomonic features clinch diagnosis

COMMON TRAPS

✗Not being systematic in approach

✗Forgetting to assess the spine

✗Missing subtle density changes

VIVA SCENARIOChallenging

EXAMINER

"Tests knowledge of evidence-based management in skeletal dysplasia."

EXCEPTIONAL ANSWER

Bisphosphonates are the mainstay of medical management for moderate to severe osteogenesis imperfecta. The Cochrane review by Dwan et al. analyzed 14 RCTs and found that bisphosphonates consistently increase bone mineral density in children with OI. However, the evidence for fracture reduction is more limited and less consistent. Both IV (pamidronate, zoledronic acid) and oral (alendronate, risedronate) bisphosphonates are effective for increasing BMD. Cyclical IV pamidronate is commonly used in severe OI - typically 3 days every 3-4 months. Benefits must be weighed against theoretical concerns including atypical fractures, osteonecrosis of jaw, and effects on growing skeleton. Current practice is to use bisphosphonates in moderate-severe OI (Types III, IV) but not necessarily in mild Type I unless frequent fractures occur.

KEY POINTS TO SCORE

Bisphosphonates increase BMD consistently

Fracture reduction evidence is limited

IV pamidronate common for severe OI

Type I may not need treatment if fractures rare

Long-term effects in children still being studied

COMMON TRAPS

✗Claiming bisphosphonates definitively reduce fractures

✗Not knowing the Cochrane evidence

✗Treating all OI types the same way

MCQ Practice Points

Exam Pearl

Q: What is the most common skeletal dysplasia and its genetic basis? A: Achondroplasia, caused by gain-of-function mutation in FGFR3 (fibroblast growth factor receptor 3). This mutation inhibits chondrocyte proliferation in the growth plate, causing rhizomelic (proximal) limb shortening with normal trunk length.

Exam Pearl

Q: What is the life-threatening complication of achondroplasia in infancy? A: Foramen magnum stenosis causing cervicomedullary compression. The small foramen magnum combined with atlantoaxial instability can cause brainstem compression, central apnea, and sudden death. MRI screening is recommended in the first 2 years.

Exam Pearl

Q: How do you distinguish spondyloepiphyseal dysplasia (SED) from multiple epiphyseal dysplasia (MED)? A: SED has short trunk with vertebral involvement (platyspondyly) plus epiphyseal abnormalities. MED has normal trunk height with only epiphyseal involvement. Both cause premature osteoarthritis, but SED patients are shorter and have spinal deformity.

Exam Pearl

Q: What orthopaedic complications are common in achondroplasia? A: Spinal stenosis (lumbar, may need multilevel decompression), foramen magnum stenosis (cervical), thoracolumbar kyphosis (often self-corrects), genu varum (tibial bowing), and atlantoaxial instability. Hip and knee arthroplasty may be challenging due to anatomic variants.

Australian Context

Australian Referral Centres

Tertiary Paediatric Hospitals:

Royal Children's Hospital Melbourne - Skeletal Dysplasia Clinic
The Children's Hospital Westmead - Bone and Mineral Service
Queensland Children's Hospital
Perth Children's Hospital

Adult Transition:

Transition to adult metabolic bone services
Continuity of genetic and orthopaedic care
Multidisciplinary approach maintained

PBS and Access

Bisphosphonates (OI):

Pamidronate and zoledronic acid PBS listed for OI
Authority required prescription
Specialist initiated

Enzyme Replacement (MPS):

Life Saving Drugs Program (LSDP) for eligible MPS patients
Laronidase, idursulfase, elosulfase alfa available
Strict eligibility and monitoring criteria

Vosoritide:

TGA approved for achondroplasia (2022)
Currently not PBS listed
Access through patient access programs

Exam Relevance

For the Australian orthopaedic exam, you must be able to recognize common skeletal dysplasias radiographically, understand the orthopaedic complications of achondroplasia and OI, know the principles of rodding in OI, and recognize cervical instability risks in MPS/SED. Classification by bone density and location is a common viva framework.