a comprehensive review of Achondroplasia, Hypochondroplasia and Spondyloepiphyseal Dysplasia and their manifestation and differences

1. Achondroplasia, Hypochondroplasia
and Spondyloepiphyseal Dysplasia
Dr. Sairamakrishnan S

2. ACHONDROPLASIA

3. • Achondroplasia is the most common form of
dwarfism
• Incidence range between 1.3 per 100,000 live
births and 1.5 per 10,000 live births

4. Genetics
• Inherited as an autosomal dominant trait with
complete penetrance
• The usual patient with achondroplasia is
heterozygous in genotype
• In homozygous cases, achondroplasia is
usually fatal in the neonatal period

5. • The gene for achondroplasia encodes for
FGFR-3 and is located on chromosome 4p
• The abnormality in the gene is a glycine-to-
arginine substitution
• Overactivity of the receptor's function
• Mutation is the same for all patients
• FGFR is expressed in all prebone cartilage, and
its function is to slow down or inhibit
enchondral ossification.

6. • Recent research has found that FGFR-3
overexpression inhibits parathyroid hormone–
related peptide, resulting in abnormal
apoptosis of chondrocytes

7. Pathophysiology
• Failure of enchondral ossification,
endomembranous ossification is normal
• With loss of columnization and loss of normal
chondrocyte proliferation
• Fibrous tissue is present in the zone of
provisional calcification
• The bones remain short
• The bones are of normal diameter

8. Clinical Features
• Short stature
• Apparent at birth
• Trunk length normal, arm span
and standing height are reduced
• Shortening is most severe in the
proximal limbs - rhizomelic
micromelia.

9. • frontal bossing
• small maxillae
• relatively prominent mandibles
• apparent enlargement of the head
• nasal bridge is depressed and
flattened

10. • hands are short and broad
• all of the digits are of
equal length - starfish
hand
• separation between the
middle and ring fingers –
trident hand

11. • upper limbs are short, and flexion
contractures of the elbows may be present
• lower limbs also are short and may be bowed
in varus
• patient may have a waddling gait
• soft tissue abundance
• normal intelligence

12. Radiology
• shortness of the tubular long bones
• metaphyses are widened and flared
• growth plates are U-shaped or V-shaped –
best seen in distal femur

14. • the pelvis characteristically appears broad and
flat, with squared iliac wings
• flattening of the acetabula
• width of the pelvic inlet is greater than its
depth – champagne glass appearance
• proximal femoral metaphyses are widened
and the femoral necks are short
• Coxa vara developes

16. • In spine, spinal canal narrows and the
interpedicular distance decreases due to
premature synostosis between the vertebral
bodies and their arches
• Scaloping of posterior vertebral bodies

18. Treatment
• Growth hormone therapy – effective in some
patients
• Limb lengthening procedures – contovercial
• Correction of genu valgum
• Correction of kyphotic deformity – orthosis or
stabilisation

19. HYPOCHONDROPLASIA

20. • rare form of dwarfism that resembles
achondroplasia but is less severe
• hypochondroplasia is transmitted as an
autosomal dominant trait, and its gene defect
encodes for FGFR-3

21. Clinical features
• cannot be detected at birth
• If mild remains undetected throught life
• body disproportion may not be apparent until
puberty
• Life span is normal

22. Hall’s criteria
Primary criteria
• a narrowed or unchanged lumbar
interpedicular distance
• squared, shortened ilia
• a short, broad femoral neck
• short tubular bones, with metaphyseal flaring
• mild to moderate brachydactyly.

23. Secondary criteria are
(1) AP shortening of lumbar pedicles
(2) dorsal concavity of the lumbar spine
(3) a long distal fibula
(4) a short distal ulna
(5) a long ulnar styloid

24. Treatment
• Growth hormone is used with greater success
than in achondroplasia
• Ideally started arround puberty

25. SPONDYLOEPIPHYSEAL DYSPLASIA

26. • Spondyloepiphyseal dysplasia (SED) is
characterized by disproportionate dwarfism
with progressive involvement of the spine and
epiphyses of the long bones.
• There are two major types of SED. The
congenita type is detectable at birth, whereas
a milder tarda type presents later in childhood

27. SPONDYLOEPIPHYSEAL DYSPLASIA
CONGENITA

28. • Spondyloepiphyseal dysplasia congenita
results in obvious short-trunk dwarfism and
variable degrees of coxa vara, with abnormal
epiphyses and vertebral flattening.
• Shortening is rhizomelic and mesomelic, with
relative sparing of the hands and feet.

29. Genetics
• Autosomal dominant transmission
• Mutations in the COL2A1 locus on
chromosome 12, which encodes the type II
procollagen α1 chain.
• This results in abnormal type II collagen

30. Clinical features
• Short stature
• eyes are wide-set
• neck is short
• chest appears barrel shaped
• genu valgum
• coxa vara
• Exaggerated lumbar lardosis
• waddling gait
• Premature OA

31. • Associated anomalies in SED congenita
– cleft palate
– myopia with retinal detachment
– Cataracts
– Deafness
– herniae

33. Radiographic findings
• Delayed appearance of epiphysis and
secondary centres
• Femoral head does not appear till 5 years of
age
• When epiphysis appear they appear flat and
irregular
• Hands and feet appear normal in length
• Coxa vara with horizontal acetabula

35. • Platyspondyly
• Kyphoscoliosis
• Odontoid hypoplasia

37. Management
• Orthopaedic treatment begins with the
cervical spine.
• Signs of cervical instability include hypotonia,
sleep apnea, respiratory insufficiency, and
myelopathy.
• Respiratory insufficiency has been seen in
infants with SED congenita secondary to
thoracic dysplasia and cervical cord
compression

38. • Kyphoscoliosis may require bracing but if
severe may require stabilisation
• Correction of coxa vara with femoral and
acetabular osteotomies
• Genu valgum correction – distal femoral
osteotomy

39. SPONDYLOEPIPHYSEAL DYSPLASIA
TARDA

40. • Spondyloepiphyseal dysplasia tarda is a milder
form of SED that is not clinically apparent at
birth
• Height is only minimally affected

41. • autosomal recessive or X-linked recessive
inheritance
• SEDL gene in the Xp22 region
• SEDL codes for the protein sedlin, which is
important in endoplasmic reticulum–Golgi
vesicular transport

42. Clinical features
• Hip pain – main presenting complaint
• diminished height
• barrel chest deformity
• early hip arthrosis

43. Radiography
• Coxa magna with flattening and extrusion can
be seen on pelvic radiographs
• Platyspondyly with narrowed disc spaces

46. Management
• Orthopaedic management is directed at
treating the precocious hip arthritis
• Valgus osteotomy of the proximal femur in
young patients
• THR in adulthood
• If odontoid hypoplasia is present stabilization
may be needed
• Orthosis for kyphoscoliotic deformity, rarely
stabilization