It occurs due to sporadic mutations in the majority of cases but can be inherited as an autosomal dominant condition. Homozygous achondroplasia is lethal.
There is a prevalence of approximately 1 in 25,000-50,000 births with males affected more frequently than females 18.
Achondroplasia is the most common cause of short-limb dwarfism. Patients are of normal intelligence with normal motor function. However, they may have specific neurologic deficits.
The disease results from a mutation in the fibroblast growth factor gene 3 (FGFR3) located on chromosome 4p16.3 which causes abnormal cartilage formation. These are cell surface receptors comprised of an extracellular domain with three immunoglobulin like regions, a transmembrane domain and an intracellular tyrosine kinase 19.
The mutation to the FGFR3 gene in achondroplasia is a gain of function mutation with constitutive activation of an inhibitory signal 19,20. All bones that form by endochondral ossification are affected. Bones that form by membranous ossification are not affected, thus allowing the skull vault to develop normally.
- SADDAN syndrome: severe achondroplasia with developmental delay and acanthosis nigricans
Almost all the bones of the skeleton are affected, and hence all parts of the body have bony changes with secondary soft tissue changes. Antenatally it is difficult to diagnose achondroplastic features until the 3rd trimester 13.
Antenatally detectable sonographic features include:
- short femur length measurement: often well below the 5th centile
- the femur length (FL) to biparietal diameter (BPD) is taken as a useful measurement
- trident hand 11: 2,3 and 4 fingers appearing separated and similar in length
- separation of 1st, 2nd, 3rd and 4th fingers
- protruding forehead: frontal bossing
- depressed nasal bridge
Features on radiographs, CT, and MRI are similar and discussed together here.
- relatively large cranial vault with small skull base
- frontal bossing with the depressed nasal bridge (midfacial retrusion) 19
- narrowed foramen magnum
- cervico-medullary kink
- relative elevation of the brainstem resulting in a large suprasellar cistern and vertically-oriented straight sinus
- communicating hydrocephalus (due to venous obstruction at sigmoid sinus)
- large anterior fontanelle in infancy, may persist to 5 or 6 years of age 19
Also, see the achondroplastic base of skull abnormalities for further discussion.
- posterior vertebral scalloping
- progressive decrease in the interpedicular distance in the lumbar spine
- gibbus: thoracolumbar kyphosis with bullet-shaped/hypoplastic vertebra (not to be confused with Hurler syndrome)
- short pedicle canal stenosis
- laminar thickening
- widening of intervertebral discs 8
- an increased angle between the sacrum and lumbar spine
- anterior flaring of the ribs
- anteroposterior narrowing of the ribs
Pelvis and hips
- horizontal acetabular roof (decreased acetabular angle)
- small squared (tombstone or mickey mouse ear) iliac wings
- small trident pelvis
- champagne glass type pelvic inlet
- short sacroiliac notches
- metaphyseal flaring 8: can give a trumpet bone type appearance
- the femora and humeri are particularly shortened (rhizomelic shortening)
- long fibula: the fibular head is at the level of the tibial plateau (case 3)
- bowing to mesial segment of legs 19
- the limbs may also appear thickened but are in fact normal in absolute terms; thickening is perceived due to reduced length
- trident hand
- chevron sign 16,17
- the metacarpal and metatarsal bones, and in some cases the proximal phalanges, are short and of similar length
Treatment and 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 6-7.
Overall prognosis is good, with near-normal life expectancy in heterozygous individuals. When homozygous, the condition is fatal due to respiratory failure 7.
History and etymology
Achondroplasia literally means "without cartilage formation", although the pathology is impaired endochondral ossification (see Pathology above).
The differential diagnosis is that of other less common skeletal dysplasias, including 6:
- campomelic dysplasia
- thanatophoric dysplasia
- chondroectodermal dysplasia (Ellis-van Creveld syndrome)
- 1. Kao SC, Waziri MH, Smith WL et-al. MR imaging of the craniovertebral junction, cranium, and brain in children with achondroplasia. AJR Am J Roentgenol. 1989;153 (3): 565-9. AJR Am J Roentgenol (abstract) - Pubmed citation
- 2. Wang H, Rosenbaum AE, Reid CS et-al. Pediatric patients with achondroplasia: CT evaluation of the craniocervical junction. Radiology. 1987;164 (2): 515-9. Radiology (abstract) - Pubmed citation
- 3. Wynn J, King TM, Gambello MJ et-al. Mortality in achondroplasia study: a 42-year follow-up. Am. J. Med. Genet. A. 2007;143A (21): 2502-11. doi:10.1002/ajmg.a.31919 - Pubmed citation
- 4. Galarza M, López-Guerrero AL, Martínez-Lage JF. Posterior fossa arachnoid cysts and cerebellar tonsillar descent: short review. 2010;doi:10.1007/s10143-010-0262-9 - Pubmed citation
- 5. Reeder MM, Felson B. Reeder and Felson's gamuts in radiology, comprehensive lists of roentgen differential diagnosis. Springer Verlag. (2003) ISBN:0387955887. Read it at Google Books - Find it at Amazon
- 6. Moreland LW. Rheumatology and immunology therapy, A to Z essentials. Springer Verlag. (2004) ISBN:3540206256. Read it at Google Books - Find it at Amazon
- 7. Moreland LW. Rheumatology and immunology therapy, A to Z essentials. Springer Verlag. (2004) ISBN:3540206256. Read it at Google Books - Find it at Amazon
- 8. Cheema JI, Grissom LE, Harcke HT. Radiographic characteristics of lower-extremity bowing in children. Radiographics. 23 (4): 871-80. doi:10.1148/rg.234025149 - Pubmed citation
- 9. Dighe M, Fligner C, Cheng E et-al. Fetal skeletal dysplasia: an approach to diagnosis with illustrative cases. Radiographics. 28 (4): 1061-77. doi:10.1148/rg.284075122 - Pubmed citation
- 10. Bowerman RA. Anomalies of the fetal skeleton: sonographic findings. AJR Am J Roentgenol. 1995;164 (4): 973-9. AJR Am J Roentgenol (abstract) - Pubmed citation
- 11. Bromley B, Benacerraf B. Abnormalities of the hands and feet in the fetus: sonographic findings. AJR Am J Roentgenol. 1995;165 (5): 1239-43. AJR Am J Roentgenol (abstract) - Pubmed citation
- 12. Entezami M, Albig M, Knoll U et-al. Ultrasound Diagnosis of Fetal Anomalies. Thieme. (2003) ISBN:1588902129. Read it at Google Books - Find it at Amazon
- 13. Schramm T, Gloning KP, Minderer S et-al. Prenatal sonographic diagnosis of skeletal dysplasias. Ultrasound Obstet Gynecol. 2009;34 (2): 160-70. doi:10.1002/uog.6359 - Pubmed citation
- 14. Thijn CJ. Radiology of the Hand. Springer Science & Business Media. (2012) ISBN:3642509665. Read it at Google Books - Find it at Amazon
- 15. Jana M, Nair N, Gupta AK, Kabra M, Gupta N. Pelvic radiograph in skeletal dysplasias: An approach. The Indian journal of radiology & imaging. 27 (2): 187-199. doi:10.4103/ijri.IJRI_367_16 - Pubmed
- 16. Grainger & Allison's Diagnostic Radiology Essentials 2nd Edition; Lee A Grant, Nyree Griffin, 2019 ISBN-13: 978-0702073113
- 17. Panda A, Gamanagatti S, Jana M, Gupta AK. Skeletal dysplasias: A radiographic approach and review of common non-lethal skeletal dysplasias. (2014) World journal of radiology. 6 (10): 808-25. doi:10.4329/wjr.v6.i10.808 - Pubmed
- 18. Ireland PJ, Pacey V, Zankl A, Edwards P, Johnston LM, Savarirayan R. Optimal management of complications associated with achondroplasia. (2014) The application of clinical genetics. 7: 117-25. doi:10.2147/TACG.S51485 - Pubmed
- 19. Achondroplasia: a comprehensive clinical review. (2019) Orphanet Journal of Rare Diseases. 14 (1): 1. doi:10.1186/s13023-018-0972-6 - Pubmed
- 20. Webster MK, Donoghue DJ. Constitutive activation of fibroblast growth factor receptor 3 by the transmembrane domain point mutation found in achondroplasia. (1996) The EMBO journal. 15 (3): 520-7. Pubmed