Genetics of Achondroplasia Treatment & Management

Updated: Jan 10, 2022
  • Author: Germaine L Defendi, MD, MS, FAAP; Chief Editor: Maria Descartes, MD  more...
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Medical Care

Closely monitor body growth in patients with achondroplasia using achondroplasia-specific growth charts. Weight, height, and head circumference should be measured and plotted monthly for the first year of life. Measure and record the upper-to-lower segment ratio.

Monitor developmental milestones in gross and fine motor skills, language, and social/adaptive development.

Perform thorough neurologic examinations.

Diagnose and treat middle ear infections, as recurrence can lead to conductive hearing loss.

Orthodontic evaluation should be performed to assess for dental malocclusion and crowding.

Weight management should be instituted to prevent obesity and its associated comorbidities.

Recombinant human growth hormone (r-hGH or HGH) therapy should be administered to foster linear growth. Treatment with r-hGH therapy effectively increases the bone growth rate, especially for the first year of use. Initiating therapy at age 1-6 years is recommended to achieve maximum growth benefit. Long-term studies to determine final height and randomized, controlled studies to justify prolonged treatment with r-hGH in patients with short stature are presently not available. [27]

Anti-inflammatory agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs), are useful to decrease pain and inflammation in patients with degenerative joint disease.

C-type natriuretic peptides

Vosoritide, a biologic analogue of C-type natriuretic peptide (CNP), prevents the inhibition of chondrocyte mineralization resulting from FGFR3 mutation. Targeted at boosting linear growth, the agent is indicated for pediatric patients aged 5 years or older who have achondroplasia with open epiphyses.

In binding to natriuretic-peptide receptor B (NPR-B), CNP induces cyclic guanosine monophosphate (cGMP) synthesis. This inhibits the mitogen-activated protein kinase (MAPK) pathway, resulting in increased extracellular matrix (ECM), which, in conjunction with chondrocytes, serves as a template for bone via endochondral ossification. Achondroplasia results when the FGFR3 protein, due to a mutation in the encoding gene, becomes permanently active. By activating two intracellular signaling cascades, FGFR3 signaling reduces the proliferation and differentiation of bone growth plate chondrocytes, through the signal transducer and activator of transcription 1 (STAT1) pathway, and diminishes ECM production, through the MAPK pathway.

Approval was supported by outcomes of a global randomized, double-blind, placebo-controlled phase 3 study in which 121 children with achondroplasia, aged 5-14 years, were enrolled. By 1 year, annualized growth velocity (AGV) had changed from baseline by -0.17 cm/year for the placebo-treated patients and by 1.40 cm/year for the patients who received vosoritide, giving the latter group a statistically significant improvement of 1.57 cm/year. After the study, an open-label extension for 58 patients initially randomized to vosoritide found that improvement in AGV was maintained at 2 years. [28, 29]



Immediately refer patients to a neurologist and/or neurosurgeon for reflex asymmetry, profound hypotonia, early hand preference, or significant head circumference growth.

Depending on clinical concerns, referrals to pediatric specialists, such as an otolaryngologist, orthopedist, and pulmonologist, may be needed. 

A pediatric endocrinologist, with knowledge of r-hGH treatment protocol, can give guidance to parents about r-hGH as a therapeutic option to increase linear height. 

Dietary guidance by a nutritionist to maintain healthy weight goals may be helpful.

Refer to geneticists and genetic counselors for prenatal consultations, options for genetic testing, and resources for support organizations.

Offer psychological support and educational tools to patients and their caregivers to assist in coping with disproportionate short stature.



Hunter et al recommend that children with achondroplasia remain within 1 standard deviation of the mean weight/height (W/H) curve for people with achondroplasia. 

Sex- and age-specific body mass index (BMI) curves are available and should be used for patients with achondroplasia (birth to age 16 y) for health surveillance and nutritional guidance. Dietary guidance by a nutritionist to help maintain healthy weight goals is helpful.

Patients with elevated BMIs have increased risk of comorbidities as associated with their skeletal dysplasia and impact of excess weight (eg, cardiovascular disease, sleep apnea, diabetes, and skeletal burden). [30]


Surgical Options

Leg-lengthening procedures using distraction osteogenesis have been performed successfully. These procedures are lengthy, traumatic, and very demanding for both the patient and his or her family. Complications include bone infection, injury to nerves/blood vessels, injury to muscles/tendons, poor bone healing, and unequal lengthening.

An average leg-length gain of about 18 cm and an average increase in arm length of about 10 cm has been reported. Combining both r-hGH therapy and lengthening surgery may provide optimal benefit for patients in achieving near-normal stature and proportions. Successful height increase is reported to be 12-14 inches. Good outcomes are reported with the use of the Orthofix Garches lengthening device, along with tenotomy of the Achilles tendon and syndesmosis. This procedure has fewer complications and demonstrates healing indices similar to those of other operative protocols. Another procedure associated with few complications in children and adolescents (< 14 y) is tibia lengthening, rather than femur lengthening.

Children with signs of craniomedullary compression may require surgical treatment to release this compression to improve neurologic, cognitive, and respiratory functions. [31] Medical indications for suboccipital decompression include lower limb hyperreflexia or clonus on neurologic examination, central hypopnea demonstrated by polysomnography, and foramen magnum measurements lower than the mean values.

Lumbar laminectomy can be performed for spinal stenosis, which is a condition that tends to occur in early adulthood.

Spinal fusion can be performed for persistent kyphosis not improved with bracing and sitting modification.