Achondroplasia

Definition/Description

Achondroplasia is a rare congenital disease which predominantly affects the long bones of the body. Most cases are from an autosomal dominant inherited fibroblast growth factor receptor-3 (FGFR3) gene which has been mutated. "In endochondral bone development, the mutation increases the fibroblast growth factor receptor-3 signaling, which interferes with chondrocyte proliferation and differentiation, adversely affecting the epiphysial (growth) plates."[1]

Prevalence

Achondroplasia is the most commonly reported form of dwarfism. According to a study performed in 2008 by Waller and colleagues "the prevalence of achondroplasia ranged from 0.36 to 0.60 per 10,000 livebirths."[2] June et al found that "approximately 98% of patients with achondroplasia have a mutation resulting from G-to-A substitution in the FGFR3 gene; the majority of cases result from a sporadic, de novo mutation."[1] Almost all of the cases of achondroplasia, therefore, are a result of a gene mutation during development in the womb.

Characteristics/Clinical Presentation

The FGFR3 gene mutation leads to shortened extremities which are often bowed in appearance especially in the lower extremities. The individual's trunk is normal in size, however affected persons exhibit an enlarged skull. "Affected individuals can exhibit short stature with rhizomelic (proximal) shortening of the arms and legs, a normal-size trunk with larger heads and frontal bossing, limited elbow extension, bowed legs, spinal kyphosis or lordosis, and spinal stenosis."[1] Per
X-ray showing lower extremity bowing commonly seen in individuals with achondroplasia. (nemours.org)
sons with achondroplasia also exhibit decreased growth in the vertebral bodies leading to spinal changes that can predispose the individual to conditions affecting the spinal nerves. Other common symptoms found in achondroplastic dwarfism include:
  • "abnormal" hand appearance with persistent space between the long and ring fingers
  • bowed legs
  • decreased muscle tone
  • disproportionately large head-to-body size difference
  • prominent forehead (frontal bossing)
  • shortened arms and legs (especially the upper arm and thigh)
  • short stature (significantly below the average height for a person of the same age and sex)
  • spinal stenosis
  • spine curvatures called kyphosis and lordosis."[3]

Associated Co-morbidities

  • Clubbed feet
  • Hydrocephalus[3]
  • Otitis media which may lead to conductive hearing loss
  • Adenotonsillar hypertrophy which when combined predisposes the individual to upper airway obstruction[4]

Medications

Although there have been no studies which support its use long term, growth hormone has been used in some individuals to promote growth and therefore increase the person's height. The theory behind this hormone therapy is that growth hormone "stimulates growth of linear bone, skeletal muscle, and organs."[4]

Diagnostic Tests/Lab Tests/Lab Values

There are diagnostic tests which may be performed both before and after birth of the individual suspected to suffer from achondroplasia. A prenatal ultrasound of an infant may show signs of excessive amniotic fluid in the womb in cases of achondroplasia. After the infant is born, the front-to-back head size of the newborn is increased when compared to non-affected newborns. The child may also show signs of hydrocephalus. X-rays of the infant may also be used to diagnos achondroplasia as the long bones show changes from those x-rays of non-affected infants.[5]

Etiology/Causes

Achondroplasia is most commonly the result of a genetic anomaly from the fibroblast growth factor receptor-3 (FGFR3) gene. The gene is responsible for inhibiting osteoblasts, and in individuals with achondroplasia this mutation affects the epiphysial growth plates during development. "In endochondral bone development, the mutation increase the fibroblast
FGFR3 gene mutation is the most common cause of achondroplasia. (passionfilms.com.mx)
growth factor receptor-3 signaling, which interferes with chondrocyte proliferation and differentiation, adversely affecting the epiphysial (growth) plates." [1]

Some studies have also looked at the effect of the parents' age and the increased prevalence of achondroplasia. "In Texas, fathers that were 25-29, 30-34, 35-39, and greater than or equal to 40 years of age had significantly increased rates of de novo achondroplasia among their offspring compared with younger fathers." [2]

Systemic Involvement

Due to the significant involvement of the musculoskeletal system with achondroplasia, many individuals with the condition suffer from various skeletal issues such as degenerative joint disease, osteoarthritis, excessive wear of cartilaginous surfaces, etc. Some of the more common complications that a person with achondroplasia may need treatment for are listed below. These and many other complications, including cardiopulmonary issues, can occur secondary to the dysplastic changes that occur with achondroplasia.

  • Foramen magnum stenosis which may lead to cervicomedullary compression and central apneas
  • Lumbar spinal stenosis which can lead to neurologic deficits such as claudication and incontinence
  • Thoracic deformities may cause restrictive lung disease[4]

Medical Management (current best evidence)

There are no direct medical treatments for achondroplasia. However there are many medical treatments for other disorders that may develop as a direct or indirect result of achondroplasia. Because otitis media is a commonly associated condition, medical management will likely be taken to treat it. Screening for hearing loss should also be routinely performed for the same reason. Upper respiratory illnesses are also typical among individuals with achondroplasia and thus medications and other treatments may be given for the management of these issues. The same abnormal development of the skull that predisposes the individual to upper respiratory issues may also lead to dental issues. Therefore, persons with achondroplasia may require the care of an orthodontist to correct malocclusions and crowding.[4]

Individuals should be routinely screened for other commonly associated conditions so that the appropriate treatment may be provided. Such conditions include but are not limited to spinal stenosis, degenerative joint disease, neurological changes at the spinal root level, and osteoarthritis. Many of these conditions may need to be treated with surgical interventions if left untreated with conservative methods for long periods of time or if conservative treatment does not improve the patient's symptoms.

Physical Therapy Management (current best evidence)

As with the medical management of achondroplasia, there is no physical therapy management directly for the condition. However, due to the extensive list of possible co-morbidities, physical therapy will most likely be indicated for an individual with achondroplasia at some point within their lifespan. Perhaps the most likely indication for physical therapy is for the management of symptoms developed from spinal stenosis from either the cervical or lumbar spine. Because the incidence of this complication is quite large within the population of people with achondroplasia, screening of neurological signs and symptoms should be included in all examinations for this group.

The dysplastic nature of this population's skeletal system makes them predisposed to a number of degenerative disorders for which physical therapy management can be of use. Individuals with achondroplasia may be referred to physical therapy with osteoarthritis and degenerative joint disease. As a result of these progressive conditions, individuals may have undergone a surgical procedure such as spinal fusion or joint replacement. Physical therapy may be involved before surgery as a conservative treatment to help reduce pain, strengthen the patient's musculature and maybe eliminate the need for surgery all together. Post-operatively physical therapy can be used to rehabilitate patients back to their pre-morbid status.

Another important role that physical therapy can play in the role of the lives of persons with achondroplasia is in prevention. Physcial therapy can help to prevent the "wear and tear" on individuals with achondroplasia by teaching them compensatory motions, energy-saving methods, and more efficient ways of performing their daily tasks. Physical therapy can also help these individuals and their families to make modifications around the home to make their daily tasks easier and perhaps decrease their risk of some of the degenerative changes so commonly found in this population.

Alternative/Holistic Management (Current Best Evidence)

The use of growth hormone to help promote growth in individuals with achondroplasia is perhaps the most common alternative/holistic management technique currently being used. Because there are various complications and co-morbidities which can develop from achondroplasia, there too are many holistic treatments which can be applied to someone with these conditions.

nydailynews.com
There are also many support groups which can help with the various issues that a person with achondroplasia may face. Some of these groups are online, some meet in person, and some even hold national conferences every year. The links be low are just a few examples of some support groups for achondroplasia and other forms of dwarfism.

staff.jccc.edu/pdecell/heverman/support%20groups.htm

www.shortsupport.org/Health/Dwarfism.html

www.dailystrength.org/c/Achondroplasia-Dwarfism/support-group

Differential Diagnosis

Conditions that may be confused with achondroplasia include achondrogenesis; chondroectodermal dysplasia; asphyxiating thoracic dystrophy; osteogenesis imperfecta; congenital hypophosphatasia; metatrophic dysplasia; Roberts syndrome; diastrophic dysplasia; short rib-polydactyly syndrome types I, II, and III; spondyloepiphyseal dysplasia congenita (camptomelic dysplasia); thanatophoric dysplasia; fibrochondrogenesis; chondrodysplasia punctate (rhizomelic type); Kniest dysplasia; mesomelic and acromesomelic dysplasia; hypochondroplasia; pseudoachondroplasia; and double heterozygosity in bone growth disorders.[6]

milesforbabies.org

Some other differential diagnoses which may considered when working with an individual with achondroplasia:

  • Rickets
  • Osteomalcia
  • Bruck syndrome
  • Juvenile Paget Disease[7]

Case Reports/Case Studies

www.gwumc.edu/edu/obgyn/genetics/casestudies/Achondroplasia.pdf (case study)

www.roneurosurgery.eu/atdoc/9IliescuBSevereSpinal.pdf (case report on severe spinal stenosis)

Resources

Support groups for achondroplasia and other forms of dwarfism:

Recent Related Research (from Pubmed)

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References

  1. 1.0 1.1 1.2 1.3 June Yoshii, BS, and Vincent C, Traynelis, MD. Achondroplasia and cervical laminoplasty Case report. J Neurosurg Spine 2009; 11:417-420. http://thejns.org/doi/pdf/10.3171/2009.4.SPINE09164 (accessed on Apr 2011).
  2. 2.0 2.1 Waller DK, Correa A, Vo TM, Wang Y, Hobbs C, Langlois PH, Pearson K, Romitti PA, Shaw GM, Hecht JT. The population-based prevalence of achondroplasia and thanatophoric dysplasia in selected regions of the US. Am J Med Genet A 2008; 146A (18):2385-9. http://www.ncbi.nlm.nih.gov/pubmed/18698630 (accessed on Apr 2011).
  3. 3.0 3.1 PubMed Health, Diseases and Conditions. Achondroplasia. http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002544/ (accessed on April 2011).
  4. 4.0 4.1 4.2 4.3 Medscape Reference, Drugs, Conditions and Procedures. Achondroplasia Medication. http://emedicine.medscape.com/article/1258401-medication (accessed on Apr 2011).
  5. Drug Information Online, Health Professionals. Achondroplasia. http://www.drugs.com/enc/achondroplasia.html (accessed on Apr 2011).
  6. Khan, Ali Nawaz. Achondroplasia Imaging: Overview. http://emedicine.medscape.com/article/415494-overview (accessed on Apr 2011).
  7. Fehring K, Jakoi A. Case study #39: Achondroplasia. http://www.gwumc.edu/edu/obgyn/genetics/casestudies/Achondroplasia.pdf (accessed on Apr 2011).