What is achondroplasia, definition , etiology ,types of dwarfism , genetic background,clinical presentations ,history and clinical examination , differential diagnosis ,diagnostic tests ,radiological findings ,CT scan and MRI , Medical care and role of growth hormone ,Surgical care and consultation,

1. Achondroplasia
Prof. Dr. Saad S Al Ani
Prof. of Pediatrics
Senior Pediatric Consultant
Saad’s Kids Clinic
Baghdad ,Iraq
anahbaghdad@gmail.com

2. Introduction
Smoker WR, Khanna G. Imaging the craniocervical junction. Childs Nerv Syst. 2008 Oct.24
(10):1123-45.
3/27/2020
Achondroplasia
Prof. Dr. Saad S Al Ani
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Skeletal Dysplasias:
Are a heterogeneous group of disorders
characterized by intrinsic abnormalities in the
growth or remodelling of the cartilage and bone

3. Introduction
Paul RM, Legare JM. Achondroplasia .Adam MP, Ardinger HH, Pagon RA ,et al, eds.
GeneReviews [internet].Seattle : University of Washington;2018
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Achondroplasia
Prof. Dr. Saad S Al Ani
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Skeletal Dysplasias (Cont.):
They affect the skull,
spine ,and extremities
in varying degrees
They frequently cause
a disproportionately
short stature
(dwarfism)

4. Introduction
Paul RM, Legare JM. Achondroplasia .Adam MP, Ardinger HH, Pagon RA ,et al, eds.
GeneReviews [internet].Seattle : University of Washington;2018
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Achondroplasia
Prof. Dr. Saad S Al Ani
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Skeletal Dysplasias (Cont.):
The standing height
falls below the third
percentile for age
Achondroplasia is the
most common type of
short-limb
disproportionate
dwarfism

5. Anatomy
The bony
skeleton
The axial
skeleton
The appendicular
skeleton
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Prof. Dr. Saad S Al Ani
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Typical features of person with achondroplastic
dwarfism, including normal trunk with rhizomelic
shortening and genu varum.
https://emedicine.medscape.com/article/1258401-clinical

7. Anatomy (Cont.)
The axial
skeleton
The
skull
The
vertebrae
The
ribs
The
sternum
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Prof. Dr. Saad S Al Ani
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8. Anatomy
The appendicular
skeleton
The bones of the extremities
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Prof. Dr. Saad S Al Ani
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9. Pathophysiology
Dwarfing
Short limb types Short trunk types
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10. Pathophysiology (Cont.)
Short limb
types
Achondroplasia Hypochondroplasia
Metaphyseal
chondroplasia
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Achondroplasia
Prof. Dr. Saad S Al Ani
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11. Pathophysiology (Cont.)
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Prof. Dr. Saad S Al Ani
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In short limb types of
dwarfing the sitting height is
within normal range

12. Pathophysiology (Cont.)
Classification of greatest segmental involvement
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Achondroplasia
Prof. Dr. Saad S Al Ani
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Segmentalinvolvement Rhizomelic (proximal)
Mesomelic (middle)
Acromelic (distal)

13. Pathophysiology (Cont.)
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Achondroplasia
Prof. Dr. Saad S Al Ani
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In achondroplasia, the extremity
involvement is rhizomelic ,the
arms and thighs are more
severely involved than the
forearms ,legs ,hands , and feet
Laederich MB ,Horton WA. Achondroplasia :pathogenesis and implications for future
treatment. Curr Opin Pediatr.2010 Aug.22(4):516-23

14. Pathophysiology (Cont.)
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Achondroplasia
Prof. Dr. Saad S Al Ani
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In achondroplasia ;the primary
defect is abnormal endochondral
ossification
N.B.
Periosteal and intramembranous ossification is
normal

15. Pathophysiology (Cont.)
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Achondroplasia
Prof. Dr. Saad S Al Ani
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Inachondroplasia:
Tubular bones are short and broad
.
The iliac crest apophyses are normal
The growth of the triradiant cartilage
is abnormal

16. Etiology
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Achondroplasia
Prof. Dr. Saad S Al Ani
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At least 80% of cases result from a random
new mutation
In sporadic cases . a paternal age older than
36 years is common
Most parents are of average size and have NO
family history of a dwarfing condition

17. Etiology
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Achondroplasia
Prof. Dr. Saad S Al Ani
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Baitner AC ,Maurer SG , Gruen MB , Di Cesare PE . The genetic basis of the
osteochondrodysplasias. J Pediatr Orthop. 2000 Sep-Oct. 20(5):594-605.
A single gene mapped to the short arm
of chromosome 4 (band 4p16.3)
Achondroplasia is transmitted as an
autosomal dominant trait

18. Etiology (Cont.)
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Achondroplasia
Prof. Dr. Saad S Al Ani
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MutationinFGFR3(Fibroblast
growthfactorreceptor3)is
responsiblefor:
Achondroplasia
Hypochondroplasia
Thanatophoric
dysplasia

19. Etiology (Cont.)
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Achondroplasia
Prof. Dr. Saad S Al Ani
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MutationinFGFR3: Is due to transition of guanine to
adenine (G to A) at nucleotide
1138 of complimentary DNA
Causes enhancement in its fuction of
limiting endochondral ossification

20. Etiology (Cont.)
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Prof. Dr. Saad S Al Ani
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The primary function of FGFR3 is to
limit osteogenesis

21. Epidemiology
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Achondroplasia
Prof. Dr. Saad S Al Ani
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Achondroplasia Worldwide is the most common skeletal
dysplasia affecting 1 in every 40,000 children
About 80% of all dwarfs have
achondroplasia
Males and females and all races have
equal frequency

22. Prognosis
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Achondroplasia
Prof. Dr. Saad S Al Ani
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CausesofDeath
In children < 4yr.
Brainstem
compression
In individual aged 5-24yr.
Central nervous system
and
Respiratory
abnormalities

23. Prognosis (Cont.)
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Achondroplasia
Prof. Dr. Saad S Al Ani
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Morbidityassociated
withachondroplasia
Recurrent otitis
media
Neurologic complications
Obstructive and restrictive respiratory
complications

24. Prognosis (Cont.)
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Achondroplasia
Prof. Dr. Saad S Al Ani
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Morbidityassociated
withachondroplasia
(cont.)
Hydrocephalus
Spinal deformities
Obesity

25. Prognosis (Cont.)
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Achondroplasia
Prof. Dr. Saad S Al Ani
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Morbidityassociated
withachondroplasia
(Cont,)
Spinal canal stenosis
Genu varum
Cardiovascular complications

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Achondroplasia
Prof. Dr. Saad S Al Ani
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Clinical presentation
History&
Physicalexamination
Gross motor
development delay
Speech and language
problems
Cognitive skills are
preserved
Intelligence level is
within normal
Standing height is
below 3rd centile
Sitting height is within
normal limits

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Achondroplasia
Prof. Dr. Saad S Al Ani
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Clinical presentation (Cont.)
History&
Physicalexamination
Otitis media
(about 75%)
Conductive hearing loss
Dental crowding
&malocclusion
Small chest &pectus
excavatum
Joint laxity
Back pain ,leg pain
,paresthesias & incontinence

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Achondroplasia
Prof. Dr. Saad S Al Ani
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Clinical presentation (Cont.)
History&
Physicalexamination
Disproportionate short-limb dwarfism
(at birth)
Thoracolumbar kyphosis &lordosis
(before walking)
Trident hand
Spinal deformities
Spinal canal stenosis
Macrocephaly

29. Differential Diagnosis
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Prof. Dr. Saad S Al Ani
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Thanatophoric dwarfism
Chondroectodermal dysplasia (Ellis-van Creveld syndrome)
Asphyxiated thoracic dysplasia
Chondrodysplasia punctata (Conradi disease)
Pseudoachondroplastic dysplasia

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Achondroplasia
Prof. Dr. Saad S Al Ani
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Laboratory studies
DNA testing : FGFR3 Mutation
Ultrasonography: antenatally
Imaging studies
Somatosensory evoked potential (SSEP)
Pulmonary function tests
Sleep study

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Achondroplasia
Prof. Dr. Saad S Al Ani
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Imaging studies
ImagingStudies
Radiographs of
skull ,spine &
extremities
The characteristic
features
Computed
tomography (CT)
Foramen magnum size,
Spinal canal narrowness
, cross-sectional
anatomy evaluation
Magnetic
resonance
imaging (MRI)
Strongly
recommended in
infancy
Ultrasonography Late in pregnancy

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Achondroplasia
Prof. Dr. Saad S Al Ani
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Characteristic skull seen in patients with
achondroplasia, with frontal bossing, small
foramen magnum, midface hypoplasia, and
relative enlargement of skull as compared
with face.
https://emedicine.medscape.com/article/1258401-workup#c4

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Achondroplasia
Prof. Dr. Saad S Al Ani
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Progressive narrowing of coronal interpedicular
distance in lumbar spine in patients with
achondroplasia. Note characteristic shape of
pelvis with horizontal sacral position.
https://emedicine.medscape.com/article/1258401-workup#c4

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Achondroplasia
Prof. Dr. Saad S Al Ani
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Thoracolumbar kyphosis with narrow lumbar spinal
canal and concave posterior bodies in 13-month-
old child with achondroplasia.
https://emedicine.medscape.com/article/1258401-workup#c4

35. 3/27/2020
Achondroplasia
Prof. Dr. Saad S Al Ani
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Typical features of lower limbs in person
with achondroplasia, including horizontal
acetabular roofs, small sacrosciatic notches,
genu varum and ankle varum with relative
overgrowth of fibula, and inverted V-shaped
distal femoral physis.
https://emedicine.medscape.com/article/1258401-workup#c4

36. 3/27/2020
Achondroplasia
Prof. Dr. Saad S Al Ani
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MRI showing cervicomedullary
compression at foramen magnum
in patient with achondroplasia.
emedicine.medscape.com/article/1258401-workup#c4

37. Treatment & Management
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Prof. Dr. Saad S Al Ani
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Medical care
• Usage of somatotropin (recombinant human
growth hormone {GH}) is recommended to be
initiated at 1-6 years of age

38. Treatment & Management (Cont.)
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Prof. Dr. Saad S Al Ani
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Surgical care
• The most encountered orthopedic problems are
related to the spine

39. Treatment & Management(Cont.)
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Prof. Dr. Saad S Al Ani
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Orthopedic
problems
Craniocervical
stenosis
Thoracolumbar
kyphosis
Spinal stenosis
Angular deformities of
the lower extremities

40. Consultation
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Achondroplasia
Prof. Dr. Saad S Al Ani
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Orthodontist
Speech therapist
Otolaryngologist
Geneticist
Pulmonologist
Pediatrician

41. References
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Achondroplasia
Prof. Dr. Saad S Al Ani
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• Pauli RM, Legare JM. Achondroplasia. Adam MP, Ardinger HH, Pagon RA, et al, eds. GeneReviews [Internet].
Seattle: University of Washington; 2018.
• Ireland PJ, McGill J, Zankl A, et al. Functional performance in young Australian children with
achondroplasia. Dev Med Child Neurol. 2011 Oct. 53(10):944-50.
• Ireland PJ, Johnson S, Donaghey S, Johnston L, Ware RS, Zankl A, et al. Medical management of children
with achondroplasia: evaluation of an Australasian cohort aged 0-5 years. J Paediatr Child Health. 2012
May. 48 (5):443-9.
• Zaffanello M, Lo Tartaro P, Piacentini G, Cantalupo G, Gasperi E, Antoniazzi F. Sleep disordered breathing in
a cohort of children with achondroplasia: correlation between clinical and instrumental findings. Minerva
Pediatr. 2017 Dec. 69 (6):481-488.
• Xu L, Li Y, Sheng F, Xia C, Qiu Y, Zhu Z. The Efficacy of Brace Treatment for Thoracolumbar Kyphosis in
Patients with Achondroplasia. Spine (Phila Pa 1976). 2018 Feb 6
• Smoker WR, Khanna G. Imaging the craniocervical junction. Childs Nerv Syst. 2008 Oct. 24(10):1123-45
• Laederich MB, Horton WA. Achondroplasia: pathogenesis and implications for future treatment. Curr Opin
Pediatr. 2010 Aug. 22(4):516-23

42. Thank you
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Achondroplasia
Prof. Dr. Saad S Al Ani
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