Achondroplasia

 

Welcome to PT 635 Pathophysiology of Complex Patient Problems This is a wiki created by and for the students in the School of Physical Therapy at Bellarmine University in Louisville KY. Please do not edit unless you are involved in this project, but please come back in the near future to check out new information!!

Original Editors - Nora Richardson from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Lead Editors - Your name will be added here if you are a lead editor on this page.  Read more.

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 firbroblast growth factor receptor-3 signaling, which interferes with chondrocyte proliferation and differentiation, adversely affecting the epiphysial (growth) plates."

Prevalence

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." 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." 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." Persons 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."

Associated Co-morbidities

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

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."

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.

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 growth factor receptor-3 signaling, which interferes with chondrocyte proliferation and differentiation, adversely affecting the epiphysial (growth) plates."

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."

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 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
  

Medical Management (current best evidence)

add text here

Physical Therapy Management (current best evidence)

add text here

Alternative/Holistic Management (current best evidence)

add text here

Differential Diagnosis

add text here

Case Reports/ Case Studies

add links to case studies here (case studies should be added on new pages using the case study template)

Resources

www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002544/

www.nemours.org/service/medical/orthopedics/dysplasia/achondroplasia/characteristic.html

Recent Related Research (from Pubmed)

see tutorial on Adding PubMed Feed

References

see adding references tutorial.