Achondroplasia

Achondroplasia is a rare genetic bone disorder that results in dwarfism, or skeletal dysplasia, a condition that affects the bones and cartilage. It is caused by a result of a change (mutation) in the fibroblast growth factor receptor 3 (FGFR3) gene that causes it not to function properly. The condition occurs in one in every 15,000 to one in 40,000 live births1, and there are about 250,000 people in the world living with the condition. 80% of those with achondroplasia are born to parents with no familial history. Achondroplasia may appear to affect only height and long bones, but in reality, it affects many areas of the skeletal system, which affects the regular functioning of many parts of the body.

Affected individuals with achondroplasia have rhizomelic shortening of the limbs, macrocephaly, and characteristic facial features with frontal bossing and midface retrusion. In infancy, hypotonia is typical, and acquisition of developmental motor milestones is often both aberrant in pattern and delayed. Intelligence and life span are usually near normal, although craniocervical junction compression increases the risk of death in infancy. Additional complications include obstructive sleep apnea, middle ear dysfunction, kyphosis, and spinal stenosis.2

The clinical features of achondroplasia include:
  • disproportionate short stature
  • rhizomelic shortening of the limbs
  • macrocephaly with frontal bossing
  • midface hypoplasia
  • a smaller-than-average chest
  • thoracolumbar kyphosis
  • lumbar lordosis
  • hypermobile joints
  • tibial bowing
  • brachydactyly

In their first five years of life, children with achondroplasia are at 50 times higher risk of sudden infant death syndrome (SIDS) than the general population, with cervicomedullary compression as the leading cause.3

In addition to cervicomedullary compression, other complications of achondroplasia include:
  • hydrocephalus
  • ear infections
  • apnea
  • risk of heart disease
  • spinal stenosis
  • hypotonia
  • bowed legs

On October 20, 2023, the U.S. Food and Drug Administration approved BioMarin’s VOXZOGO® (vosoritide) for children under 5 years of age with achondroplasia. Before the 2023 approval, on November 19, 2021, the FDA approved VOXZOGO® for injection, indicated to increase linear growth in pediatric patients with achondroplasia five years of age and older with open epiphyses (growth plates). BioMarin‘s VOXZOGO® is the first pharmaceutical treatment for achondroplasia.

Before the FDA approval of VOXZOGO®, distraction osteogenesis (limb lengthening) had been the only treatment to restore functional height (>143cm).4 In addition to VOXZOGO®, other investigational therapies are currently being researched and trialed for treating achondroplasia. Other companies are conducting research and developing/have developed pipelines for treating achondroplasia – QED therapeutics, Ascendis Pharma, TYRA Biosciences, and Sanofi.

  1. About Achondroplasia. https://www.genome.gov/Genetic-Disorders/Achondroplasia
  2. Legare JM. Achondroplasia. 1998 Oct 12 [Updated 2023 May 11]. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2023. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1152/
  3. Lifetime impact of achondroplasia: Current evidence and perspectives on the natural history. Bone, 146, 115872.
  4. Philip K. McClure, MD, FAAOS[@orthodoctorphil]. (2023, March 6). “Will the medical interventions be enough to restore functional height (>143cm) and humeral length to allow smooth activities of daily living? [Photograph]” Instagram. https://www.instagram.com/p/CpdeFTkvPhY/