Achondroplasia is the most common cause of dwarfism, occurring in 1/15,000-17,000 births. It is caused by a mutation in the FGFR3 gene that results in abnormal bone growth. Affected individuals have disproportionate short stature with a large head and short limbs. Complications can include foramen magnum stenosis, spinal stenosis, and bowed legs. Management involves surgery to address neurological or orthopedic issues and physical therapy.

1. ACHONDROPLASIA
BY
VRP

2. Achondroplasia
 Disease most
associated with
human
dwarfism
 Occurs in 1 / 15,000 –
17,000 people
 Caused by a
missense mutation

3. 2 CLINICAL VARIANTS OF
ACHONDROPLASIA
 1)hypochondroplasia/pseudoachondroplasia
 --mild ,less severe,skull not affected
 2)thanatophoric dwarfism—mutation on fgfr3 l/t cysteiene
resudues
 Severe nd lethal form

4. History
 Obvious phenotype – documented throughout history
- Ancient Egyptian artwork
- Diego Velazquez – series
of dwarf paintings in the 1600s

5. The Cause – Missense
Mutation
 Achondroplasia (ACH) is caused by a missense
mutation in FGFR3 (fibroblast growth factor
receptor 3) on chromosome 4p in humans
 In 97% of patients, an adenine replaces the normal
guanine at this position (observed in cDNA)
 3% have a cytosine instead

6. Consequence
 Both mutations result in the production of the
amino acid arginine instead of glycine
 This production of arginine enhances gene function
and increase of FGFR3 signals released
 Mitosis is promoted, but cell differentiation is
depressed due to enhancement of gene function
 Inhibits proliferation and terminal differentiation,
resulting in reduced bone growth in zone of
proliferation.

7.  Achondroplasia is the most common form of dysplasia
resulting in disproportionate dwarfism, with a reported
prevalence of 1.3 per 1000 live births.
 It is caused by defects in the FGFR3 (glycine-to-arginine
substitution) gene located on chromosome 4p.
 Although it is inherited as a fully penetrant autosomal dominant
trait, 90% of the cases are sporadic as a result of point mutation
in the gene.
 FGFR3 acts on growth plate chondrocytes to regulate linear
growth.

8.  Achondroplasia is characterized by a defect in endochondral
ossification;
 intramembranous and periosteal ossification are not
affected.
 Consequently, the lengths of long bones are reduced while
the diameter is normal.

13.  CLINICAL FEATURES
 Achondroplasia is characterized by rhizomelic
disproportionate short stature that is recognizable even in the
antenatal period by ultrasonography.
 The child has a ;
 1)disproportionately large head,
 2)short limbs
 3) trunk of normal length.

14.  4)The arm span is diminished and the fingertips reach only
to the greater trochanters.
 5)The hands are short and broad with all of the digits of equal
length and an increased web space between the middle and
ring fingers – the trident hand.
 6) Flexion contractures of the elbows, radial head dislocation,
genu varum with mild femoral bowing and internal tibial torsion
may occur.

15.  7) Kyphosis of the thoracolumbar spine is often seen in infants;
this is
 superseded by a rigid exaggerated lumbar lordosis in the
walking
 child.
 The facial features include a prominent forehead, flattened
nasal bridge and prominent mandibles

16. Antenatal ultrasound
 Antenatally detectable sonographic features include:
1)short femur length measurement: often well below the 5th centile
the femur length (FL) to biparietal diameter (BPD) is taken as a
useful measurement
 2)trident hand 1,2,3 and 4 fingers appearing separated and similar
in length AND separation of 1st, 2nd, 3rd and 4th fingers
 3)protruding forehead: frontal bossing
 4)depressed nasal bridge

17. Plain radiograph/CT/MRI Features on radiographs, CT, and MRI are similar and discussed
together here.
 Cranial
 Relatively large cranial vault with small skull
base.
Prominent forehead with the depressed nasal
bridge.
Narrowed foramen magnum.
Cervico-medullary kink.
Relative elevation of the brainstem resulting in a
large suprasellar Cistern and vertically-oriented
straight sinus.

18. Spinal
1)Posterior vertebral scalloping
2)Progressive decrease in the interpedicular distance in the lumbar spine
3)Gibbus: thoracolumbar kyphosis with bullet-shaped/hypoplastic Vertebra (not to be
confused with Hurler syndrome)
4)Short pedicle canal stenosis
5)Laminar thickening
6)Widening of intervertebral discs
7)An increased angle between the sacrum and lumbar spine-incresed lumboscral angle of
boxall

19. Chest

Anterior flaring of the ribs
Anteroposterior narrowing of the ribs

20. Pelvis and hips

1)Horizontal acetabular roof (decreased acetabular angle)
2)Small squared (tombstone or mickey mouse ear) iliac
wings
3)Small trident pelvis
4)Champagne glass type pelvic inlet
5)Short sacroiliac notches

21. Limbs
1)metaphyseal flaring : can give a trumpet bone type appearance
2)the femur and humerus are particularly shortened
(rhizomelic shortening)
3)long fibula: the fibular head is at the level of the tibial plateau
4)the limbs may also appear thickened but are in fact normal in
absolute terms; thickening is perceived due to reduced length
5)trident hand
6)chevron sign
the metacarpal and metatarsal bones, and in some cases the
proximal phalanges, are short and of similar length

22. RADIOGRAPHIC FEATURES
 Radiographs of the limbs reveal normal diaphyseal diameter but reduced
length.
 There is flaring of the metaphysis and the epiphysis is usually normal.
 The pelvis is short and wide with small sciatic notches.
 Hip radiographs show an apparent coxa vara with short femoral necks and
trochanteric overgrowth.
 In the anteroposterior view of the lumbar spine there is progressive
narrowing of the transverse interpedicular distance from L1 to L5.

23. MANAGEMENT
 Orthopaedic and neurosurgical management in achondroplasia mainly
focuses on the spinal problems.
 Stenosis of the foramen magnum leading to brainstem and cervical
cord compression can occur in infancy, which may necessitate
posterior surgical decompression.
 Hydrocephalus due to a Chiari malformation at the craniovertebral
junction may require urgent shunting..

24.  Progressive thoracolumbar kyphosis and kyphosis may require
surgery. Lumbar canal stenosis with neurogenic claudication
may become symptomatic in the adolescent.
 Symptoms include leg and back pain brought on by walking
and relieved by bending forward, which tends to reduce lumbar
lordosis and produces more space in the spinal canal.
 MRI is useful to visualize the extent of stenosis and planning
treatment in the form of laminectomy and posterior
decompression

25. Treatment
 New method of adding height, called distraction
osteogenesis, is being researched
- Lengthen tibia bone with very few risks
- Increase of 4.0 +/- 1.98 centimeters
 Growth hormone therapy is still under study
 Gene Therapy possibility
 Altered clothing, car-pedal extensions, respect from
average-sized individuals, and even a support group
all help the low self-esteem and depression that is
common

26.  Lumbar canal stenosis=decompression with laminectomy

27. prognosis

There is often a danger of cervical cord compression due to
narrowing of the foramen magnum.
Treatment varies and is usually orthopedic, particularly to
correct kyphoscolioses, as well as neurosurgical, to
decompress the foramen magnum or shunt hydrocephalus

28. Differential diagnosis
 The differential diagnosis is that of other less common skeletal
dysplasias, including :
 1)Achondrogenesis
2)Campomelic dysplasia
3)Thanatophoric dysplasia
4)Chondroectodermal dysplasia (Ellis-van Creveld syndrome