2. Dr.Virinderpal Singh Chauhan
Scope
• Definition + Terminology
• Pathogenesis
• Classification
• Some dysplasias in Detail
– Achondroplasia
– Hypochondroplasia
– Thanatotrophic dysplasia
– Kniest Dysplasia
– SED
– MED
– Cleidocranial Dysplasia
– Osteogenesis Imperfecta
3. Dr.Virinderpal Singh Chauhan
Definition + Terminology
• A.k.a Osteochondrodysplasias
• “Dys” – Disordered “Plassein” – To form
• Disorders of growth and development that affect bone and
Cartilage.
• Rare – 1:4000/5000 births
• Most result in short stature …….”??Dwarfism”
– Proportionate
– Disproportionate
• Short Limbed
• Short Trunk
5. Dr.Virinderpal Singh Chauhan
Pathogenesis
• Usually categorised into 3
……> ½ of cases
– Genetically Inherited
• Dorminant / Recessive / X-linked
– Spontaneous Mutations
– Secondary to exposure to toxic substances or
infectious agents resulting in disruption of normal
skeletal dvt
• Mechanisms
– Alteration in transcription of or intra or Extracelluar
processing of structural molecules of skeleton
– Defects in receptor/ Signal transduction pathways of
skeletal differentiation + Proliferation
6. Dr.Virinderpal Singh Chauhan
Classification
• Initially based on clinical manifestation /
radiological findings
• Rubin et al
– Acc. To anatomical distribution of bone changes
– Most of mutated genes encode proteins involved in
growth plate
• 1997
– International Nomenclature & Classification of
Osteochondrodysplasia (OCD)
• Gene + Protein defects included
• Modified in 2012 into 33 groups (OCD) & 3 groups dystocias
8. Dr.Virinderpal Singh Chauhan
Examples of Mutations
• Resting Zone
– Sox 9 mutation = camptomelic dysplasia….short
curved bone ass with sex reverse (female genetalia
not like male)
• Prolif. Zone
– FGFR3 mutation…….achondroplasia /
Hypochondroplasia / Thanatophoric dysplasia
• Hypertrophic Zone
– PTHR 1……….MED
10. Dr.Virinderpal Singh Chauhan
Prenatal Diagnosis
• Currently popular, usually 2nd Trimester
• U/s Shows shortening of skeleton
– Femur length used………..Most Common
– Other – Skull, Spine
• Additional testing can be done by Chorionic Villous Sampling +
Mutation Analysis
• Problems
– Skeletal Dysplasias Rare (Similar xtics but diff. molecularly)
– Some not apparent during 2nd trimester (only evident in 3rd or after birth)
– U/s is a limited tool (Sensitivity 40-60%, experience)
12. Dr.Virinderpal Singh Chauhan
• Commonest form of Dwarfism…….approx 1.5 : 10000 live births
• Genetics
– Autosomal Dorminant. 80-90% due to spontaneous mutation
– Risk increases with increasing paternal age (>36 yrs)
– Mutations in the gene for FGFR3. (gly for arg)
– FGFR overexpression also inhibits PTHrP causing abnormal apoptosis of chondrocytes
– The common mutations cause a gain of function of the FGFR3 gene, resulting in :
↓ Endochondral ossification.
↓ Proliferation of chondrocytes in growth plate cartilage.
↓ Cellular hypertrophy.
↓ Cartilage matrix production.
Achondroplasia
13. Dr.Virinderpal Singh Chauhan
• Short Stature………Seen at Birth
– Truncal Height Normal, Arm Span + Standing height reduced
– Rhizomelic Micromelia
– Fingertips reach Greater Trochs (normal – Mid thigh)
– Height approx 4 ft 3” males, 4ft 1” females
• Arms & Legs
– Trident Hand – Inability to approx extended middle + ring finger
– Star fish Hand – All digits of equal length
– Radial Head subluxations………..may lead to elbow contractures
– Bowed Legs (Genu varum)………Occasionally
– Relative shortening of tibia compared to fibula
– Coxa Breva like appearance due to shortening of femoral neck
• Face
– Enlarged Head with frontal bossing and mandibular protrusion
– Mid face hypoplasia ( Dental crowding / Otitis Media / Flat nose bridge / Obst. Apnea)
Clinical Features - Achondroplasia
14. Dr.Virinderpal Singh Chauhan
• Spine
– Kyphosis at Thoracolumbar jxn
• Usually corrects within a few months of ambulation
– Excessive Lordosis
• Growth & Development
– Intelligence Normal, Delayed Motor Dvt due to combo
of
• Hypotonia
• Hyper-extensible joints esp of lower limb
• Mechanical difficulty balancing large heads
• Foramen Magnum stenosis with brain stem
compression……..can be fatal
Clinical Features - Achondroplasia
15. Short Stature, Fingertips
reaching to the level of
hips
Frontal bossing,
enlargement of head
Star fish hand, Trident
hand
Dr.Virinderpal Singh Chauhan
16. Radiographic Features
, small sciatic notches,
width of pelvic inlet is
• Short tubul e in bony diameter &
density.
• Metaphyse nvolved.
• Growth plat tal femur).
• Metacarpal, hort & thick.
• Pelvis - bro
horizontal &
• Shape of p
greater tha
ar long bones, with a relative increas
s - widened & flared, epiphyses - uni
es - U or V shaped (best seen at dis
metatarsal, & phalangeal bones - s
ad & flat, squared iliac wings
notched acetabulum.
elvis - champagne glass – as
n its depth.
Dr.Virinderpal Singh Chauhan
17. Radiographic Features
• Widened proxim oral necks
are short - abno
• Ossification of p ed to more
than 1 year of ag
• Greater trochan
ossification - d
periosteal
nce.
r trochanter
• True coxa vara i
- appearance of
al femoral metaphyses, short fem
rmalities in longitudinal growth.
roximal femoral epiphysis is delay
e.
ter is normal in size as formed by
ecrease in articulotrochanteric dista
s absent, but overgrowth of greate
varus.
•
Dr.Virinderpal Singh Chauhan
18. Radiographic Features
nce from L1-L5 (Normally
40% thicker than normal
pearance
ral segment
• Spine
– Narrowing of intrapedicular dista
this increases)
– Pedicles in achondroplasia 30 –
– Vertebral Bodies – Scalloped ap
sis seen up to sac
en Magnum
frontal region to accommodate enlarging
– Lumbar Lordo
• Skull
– Smaller Foram
– Protrusion of
brain
Dr.Virinderpal Singh Chauhan
19. Dr.Virinderpal Singh Chauhan
Orthopedic Considerations
• Most related to spine
• Craniocervical Stenosis
– Commonest cause of mortality. Sympts include:
• Hypotonia
• Sleep Apnea
– Central – compression of upper cervical spinal cord
– Obstructive – upper airway obst. due to midface hypoplasia
• Hydrocephalus
– Rare in achondroplasia, communicating type
• Thoracolumbar kyphosis
– Usually seen in almost all children at thoracolumbar jxn
– As child learns to walk, muscle tone + trunk control improves =
resolution
20. Dr.Virinderpal Singh Chauhan
Management of Achondroplasia
• Usually centered around mx of complications
• Spinal Kyphosis
– Non Op… Bracing
– Op………..Ant. Corpectomy + posterior fusion (Kyp >60 by 5yrs)
• Lumbar Stenosis
– Non Op….Wt Loss, Physical therapy, Corticosteroid injections
– Op…………Laminectomy + fusion
• Foramen Magnum Stenosis
– Urgent Decompression
• Genu Valgum
– Tibial osteotomies + Hemiepiphysiodesis
• Controversial
– Growth Hormone therapy + Surgical lengthening of Limbs
21. Dr.Virinderpal Singh Chauhan
Hypochondroplasia
• Less severe form of dwarfism
• Autosomal Dorminant, 50% chance of passing to
offspring
• Mutation – FGFR3 but difference in affected a.a
(tyrosine)
• Mild forms usually undetected at birth
• Foramen Magnum stenosis + thoracolumbar stenosis
rare
22. Dr.Virinderpal Singh Chauhan
Hypochondroplasia
• Ht discrepancy less than achondroplasia
• Less pronounced facial xtics
• Mesomelic limbs
• <10% associated with Mental Retardation (unlike
Achondroplasia)
• Rx
– Surgery rare
– Growth Hormone can have +ve impact……controversial
23. Dr.Virinderpal Singh Chauhan
Thanatotropic Dysplasia
• Most lethal form of dwarfism
• Mutation – FGFR gene
• Dx fatal, all cases are spontaneous mutations
• Severe platyspondyly is the xtic feature on both u/s
and plain xrays
• Severe brain malformations seen
• Death due to cardioresp failure
24. Kniest Dysplasia
• Rare
• Autosomal dorminant
• Defect – COL1A1
• Abnormality – Type 2 collagen
• Presentation
– Disproportionate Short trunk dwarfism
– Enlarged Joints and stiffness
– Scoliosis / Kyphosis
– Cleft lip
– Flat face
– Prominent eyes due to shallow sockets
– Bell Shaped chest
Dr.Virinderpal Singh Chauhan
25. Dr.Virinderpal Singh Chauhan
Kniest Dysplasia
• Orthopedic Manifestations
– Short stature
– Club foot
– Disprop short trunk dwarfism
– Early OA
– Joint stiffness / contractures
– Scoliosis / Kyphosis
– Hypoplastic pelvis
• Medical manifestations
– Respiratory complications
– Otitis Media with hearing loss
- Cleft Palate
- Retinal Detachment
26. Kniest Dysplasia
earance of bone cartilage
one cartilage
oint contractures
rocedures for early hip degenerative
• Imaging
– Osteopenia
– Dumbell shaped metaphyseal bone
– Coxa vara
– Genu valgum
– Swiss cheese app
• Small holes in b
• Rx
– Early therapy for j
– Reconstructive p
arthritis
Dr.Virinderpal Singh Chauhan
27. Dr.Virinderpal Singh Chauhan
Spondyloepiphyseal Dysplasia
• Mutation – COL2A1
• 2 types
– SED Congenita – Autosomal dorminant – severe
– SED Tarda – X-linked, Milder form
• Usually affects vertebrae and epiphysis
28. Orthopedic Manifestations
• Short
• Short
• Barre
• Angu
• Lum
– D
– G
• Wadd
• Club
stature
neck, widespread eyes
l Shaped chest
lar deformities esp Genu Valgum
bar lordosis
ue to hip flexion contractures
ive abdomen a protrusional app
ling gait – coxa vara
foot
ciated conditions
• Asso
– Cleft Palate
– Retinal detachment
– Nephrotic syndrome - Tarda
- Cataracts
- Deafness
Dr.Virinderpal Singh Chauhan
29. • Delaye
– Fe
•
– Wh
• Coxa
• Platys
• Kypho
• Odont
– Che
Xrays
rance of epiphysis
s not seen until pt = 5ys
/12
lattened & irregular epiphysis
plasia / os odontoideum
nto-axial instability
d appea
moral head
Normal – 4-6
en seen – f
Vara
pondyly
scoliosis
oid hypo
ck for atla
Delay in ossification of femoral heads + coxa vara
Platyspondyly (flattened vertebrae)
Severe d
D
e
r
.
g
V
e
i
n
r
i
e
n
r
d
a
e
t
i
r
v
p
e
a
a
lrSti
h
n
r
gi
h
t
i
s
C
1
h
5
ay
u
r
h
o
al
n
dwith dislocated hips
30. SED
• Rx
– Atlantoaxial instability a concern
• Early occipitocervical spondylodesis
– Coxa Vara
• Valgus corrective osteotomy if angle <100 or is
progressive
– Scoliosis
• Manage operatively if angle>40
Dr.Virinderpal Singh Chauhan
31. Multiple Epiphyseal Dysplasia (MED)
– Dwarfism xtised by delayed + irreg ossification at
multiple epiphysis
– Genetic
• Defect – COMP (Cartilage Oligomeric Matrix Protein) gene
• Mutation – COL9A1/A2/A3
– Ass. With Type 2 collagenopathy since type 9 acts as link points for
type 2
• Autosomal dorminant
• Autosomal recessive – rare (Early OA/Clubfoot/multiple layered
patella/brachydactyly)
Issue – Failure of formation of secondary ossification centre
Femoral + humeDrr
.aV
i
r
li
n
hd
e
r
ep
a
alS
di
n
g
shC
ch
oa
u
mh
a
n
monlyaffected.
32. Dr.Virinderpal Singh Chauhan
• Types
– Fairbank
– Ribbing – milder form
• Clinically
– Short limbed dwarf
– Joint pains – often don’t manifest until 5-14 yrs
– Waddling gait
– Flexion contractures of knee/elbow
– SPINE + PELVIS - NORMAL
33. Xrays
• Pelvis
– Bilateral epip
• Mimics Pe
– In MED
• Knee
– Valgus knee
– Double Lay
• Due to irre
– Tibial slant si
hy
rthe
– its
ered
g o
gn
d m
seal defects
s
simultaneous + bilateral + acetab changes seen
Patella
ssification of patella
etacarpals/metatarsals
• Hand & Foot
– Short, stunte
– Hyperextensible fingers
Irregular ossification + Double
layered patella
Dr.Virinderpal Singh Chauhan
34. Dr.Virinderpal Singh Chauhan
Mx of MED
• Ortho rx rarely necessary in children
• Osteotomies to correct angular deformities
esp around knee
• Degenerative Arthritis – symptomatic rx
– ?Early THR
35. Cleidocranial Dysplasia
• Affects bones of membranous origin
• Defect – RUNX2/ CFBA1 gene (Chr 6)
– Codes for osteoblastic specific transc. Factor req for osteoblastic
differentiation
• Features
– Short Stature
– Skull bossing (front
– Maxillary region u
• Maxillary microgn
– Clavicles partially o
• Cause shoulders t
• Shoulders can be
al/parietal/occipital)
nderdvt
athia, exophthalmos
r completely absent (10%)
o drop & neck to appear large
approximated
Absent Clavicles
Dr.Virinderpal Singh Chauhan
36. Cleidocranial Dysplasia
• Pelvis h
• Coxa
• Increa
houlder
y if neck
narrow, hips may be unstable at birt
Vara + Trendelenburg Gait
sed incidence of scoliosis
implications
x for clavicles
pulothoracic arthodesis for symptomatic s
xn
a Vara rx with valgus rotational osteotom
ft angle <100
• Ortho
– No r
– Sca
dysf
– Cox
sha
– C/s often required
Dr.Virinderpal Singh Chauhan
37. Dr.Virinderpal Singh Chauhan
Osteogenesis Imperfecta
• A.k.a Fragilitus Ossium / Brittle Bone Dx
• Pathogenesis
– Impaired mutation Type 1 collagen
– Mutation – COL1A1 & COL1A2 genes
– Impaired cross links preventing production of
polymerized collagen
– Fracture Healing not impaired with large amounts of
callus formation
38. Clinical Manifestations
• Bone fragility and fractures
fractures heal in normal fashion initially
but the bone is does not remodel
can lead to progressive bowing
• Ligamentous laxity
• Short stature
• Scoliosis
• Codfish vertebrae (compressionfx)
• Olecranon apophyseal avulsion fx
Dr.Virinderpal Singh Chauhan
40. Clinical Diagnosis
• Symptoms
– Mild Cases – multiple #s during childhood
– Severe - #s at birth. Maybe fatal
• Signs
– Sabre Shin Appearance
– Bowing of bones
– Scoliosis
Dr.Virinderpal Singh Chauhan
41. Dr.Virinderpal Singh Chauhan
Classification of OI - Sillence
• Type 1
– Mildest
– Presents at Pre-school age
– Autosomal Dorminant
– Blue Sclera
– Hearing deficit in 50%
– Avulsion #s common due to decreased tensile
strength of bone
• Type 2
– Autosomal Recessive
– Lethal in perinatal period
– Blue Sclera
42. Classification of OI - Sillence
• Type 3
– Autosomal recessive
– Normal Sclera
– #s at birth
– Progressive short statu
– MOST Severe survivab
re
le form
– Xtic triangular face due to large skull and underdeveloped facial
bones
• Type 4
– Moderately severe
– Autosomal Dorminant
– Bowing of bones + Vertebrae #s common
– Normal Hearing
– White Sclera
Type 5,6,7 added to original
classification.
No real mutation but Abnormal
bone on microscopy
5 – Hypertorphic Callus after #
Dr.Virinderpal Singh Chauhan
