Achondroplasia

Disease Overview

Achondroplasia is the most commonly occurring abnormality of bone growth (skeletal dysplasia), occurring in approximately 1 in 20,000-30,000 live births. This genetic disorder is caused by a change (mutation) in the fibroblast growth factor receptor 3 (FGFR3) gene. Achondroplasia occurs as a result of a spontaneous genetic mutation in approximately 80 percent of patients; in the remaining 20 percent it is inherited from a parent. This genetic disorder is characterized by an unusually large head (macrocephaly), short upper arms (rhizomelic dwarfism), and short stature (adult height of approximately 4 feet). Achondroplasia does not typically cause impairment or deficiencies in mental abilities. If the bones that join the head and neck do not compress the brainstem or upper spinal cord (craniocervical junction compression), life expectancy is near normal.

• View Full Report Show Less
• Print / Download as PDF

• Next section >

• < Previous section
• Next section >

Synonyms

• ACH
• achondroplastic dwarfism
• dwarf, achondroplastic

• < Previous section
• Next section >

• < Previous section
• Next section >

Signs & Symptoms

General
This rare genetic disorder is characterized by distinctive features: short stature (usually under 4 feet 6 inches); an unusually large head (macrocephaly) with a prominent forehead (frontal bossing) and flat (depressed) nasal bridge; short arms and legs; prominent abdomen and buttocks (due to inward curve of the spine); and short hands with fingers that assume a “trident” or three-pronged position during extension.

Infancy
Infants born with achondroplasia typically have a “dome-like” (vaulted) skull, and a very broad forehead. In a small proportion there is excessive accumulation of fluid around the brain (hydrocephalus). Low muscle tone (hypotonia) in infancy is typical of achondroplasia. Acquisition of developmental motor milestones may be delayed.

• < Previous section
• Next section >

• < Previous section
• Next section >

Causes

Achondroplasia results from specific changes (mutations) of a gene known as fibroblast growth factor receptor 3 (FGFR3).

For most patients, there is no apparent family history of the condition. Increased age of the father (advanced paternal age) may be a contributing factor in cases of sporadic achondroplasia.

Less commonly, familial cases of achondroplasia follow an autosomal dominant pattern of inheritance. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disorder. The abnormal gene can be inherited from either parent or can be the result of a mutated (changed) gene in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.

• < Previous section
• Next section >

• < Previous section
• Next section >

Affected populations

Achondroplasia appears to affect males and females in equal numbers. This disorder begins in the developing fetus and is one of the most common forms of skeletal dysplasia that causes dwarfism. The estimated frequency of achondroplasia has ranged from about one in 15,000 to one in 35,000 births.

• < Previous section
• Next section >

• < Previous section
• Next section >

Disorders with Similar Symptoms

Symptoms of the following disorders may be similar to those of Achondroplasia. Comparisons may be useful for a differential diagnosis:

Hypochrondroplasia is a genetic disorder characterized by small stature and disproportionately short arms, legs, hands, and feet (i.e., short-limbed dwarfism). In those with the disorder, short stature often is not recognized until early to mid-childhood or, in some cases, as late as adulthood. Affected individuals may also develop bowing of the legs during early childhood that often improves spontaneously with age. In some cases, additional abnormalities may be present, such as an unusually large head (macrocephaly), a relatively prominent forehead, limited extension and rotation of the elbows, and/or other physical findings. In addition, in about 10 percent of cases, mild mental retardation may be present. In some instances, hypochondroplasia appears to occur randomly for unknown reasons (sporadically) with no apparent family history. In other cases, the disorder is familial with autosomal dominant inheritance. As noted above (see “Causes”), hypochondroplasia and achondroplasia may result from different mutations of the same gene (i.e., FGFR3). (For more information on this disorder, choose “Hypochondroplasia” as your search term in the Rare Disease Database.)

Additional disorders may be characterized by small stature and disproportionately short arms and legs (short-limbed dwarfism), abnormal enlargement of the head (macrocephaly), additional malformations of the skull and facial (craniofacial) region, and/or other symptoms and findings similar to those potentially associated with achondroplasia. Achondroplasia may be distinguished from other forms of short-limbed dwarfism through thorough clinical examination, x-ray studies, and/or additional diagnostic techniques. (For more information on these disorders, choose “dwarfism” or the exact disease name in question as your search term in the Rare Disease Database.)

• < Previous section
• Next section >

• < Previous section
• Next section >

Diagnosis

Clinical and radiologic features of achondroplasia are well-characterized. Those with typical findings generally do not need molecular genetic testing to confirm the diagnosis. When clinical features raise suspicion in a newborn, X-ray (radiography) findings can be used to help confirm the diagnosis. However, if there is uncertainty, identification of the genetic variant of the FGFR3 gene by molecular genetic testing can be used to establish the diagnosis. Below is a list adapted from Pauli and Legare (2018) that provides clinical signs that may be used in the diagnosis of achondroplasia.

• Disproportionate short stature
• Macrocephaly with frontal bossing
• Backward displacement of the midface and depressed nasal bridge
• Shortening of the arms with redundant skin folds on limbs
• Limitation of elbow extension
• Shortened fingers and toes (brachydactyly)
• Trident configuration of the hands
• Bow legs
• Exaggerated inward curve of the spine (lumbar lordosis)
• Joint laxity

• < Previous section
• Next section >

• < Previous section
• Next section >

Standard Therapies

Treatment
Recommendations for managing children with achondroplasia are outlined by the American Academy of Pediatrics Committee on Genetics, which are designed to supplement guidelines for children with average stature.

As outlined in Pauli and Legare (2018), the recommendations for the manifestations of achondroplasia include:

• Hydrocephalus: If signs/symptoms of increased intracranial pressure arise (accelerated head growth, bulging fontanelle, vision changes, headache), referral to a neurosurgeon is required. Computerized tomography (CT) or magnetic resonance imaging (MRI) of the brain in infancy may be done to determine the presence of hydrocephalus.
• Craniocervical junction constriction: Predictors of the need for suboccipital decompression require evaluation by a medical professional. Indication of symptomatic compression requires urgent referral to a neurosurgeon.
• Obstructive sleep apnea: Can be treated with weight reduction, surgery to remove tonsils and adenoids (adenotonsillectomy), positive airway pressure, and, rarely, surgery to create an opening in the neck (tracheostomy).
• Middle ear dysfunction: Ear tubes may be needed until the age of seven or eight to manage frequent middle ear infections and prevent potential hearing loss.
• Short stature: Studies on the use of growth hormone have shown initial acceleration of growth, but with lessening effect over time and little lasting benefit.
• Obesity: Measures to avoid obesity should begin in early childhood. Standard weight-by-height grids specific for achondroplasia should be used to monitor progress.
• Varus deformity: Symptomatic bowing of the legs (varus deformity) requires referral to an orthopedist. However, asymptomatic bowing does not usually warrant surgical correction.
• Spinal deformities: Preventive measures including prohibition of unsupported sitting in the first 12-18 months of life decrease risk of developing a fixed backwards curve in the mid-spine (kyphosis). Bracing or surgery may be necessary, depending on the degree of severity of such a deformity if preventive measures are unsuccessful.
• Spinal stenosis: If signs/symptoms of spinal stenosis arise, urgent surgical referral is appropriate.
• Immunization: All routine immunizations are necessary.
• Adaptive needs: Environmental modifications of the home and school may be necessary to accommodate for short stature.
• Socialization: Patients with achondroplasia may encounter difficulties in socialization and school adjustment. Support groups (such as Little People of America) can help assist families with these issues through peer support, personal example, and social awareness programs.

In 2021, Voxzogo (vosoritide) was approved for children five years of age and older with achondroplasia and open epiphyses (growth plates), allowing the potential for growth.

• < Previous section
• Next section >

• < Previous section
• Next section >

Clinical Trials and Studies

Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Toll-free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]

Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/

For information about clinical trials sponsored by private sources, contact:
http://www.centerwatch.com/

For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/

• < Previous section
• Next section >

• < Previous section
• Next section >

References

TEXTBOOKS
Pauli RM, Botto LD (2018) Achondroplasia. In: Management of Genetic Syndromes. 4 ed. New York, NY: John Wiley & Sons. In press.

JOURNAL ARTICLES
Miccoli M, Bertelloni S, Massart F. Height outcome of recombinant human growth hormone treatment in achondroplasia children: a meta-analysis. Horm Res Paediatr. 2016;86:27–34.

INTERNET
Pauli RM, Legare JM. Achondroplasia. 1998 Oct 12 [Updated 2018 May 10]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1152/ Accessed July 26, 2018.

Bober MB, Bellus GA, Nikkel SM, et al. Hypochondroplasia. 1999 Jul 15 [Updated 2013 Sep 26]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.Available from: https://www.ncbi.nlm.nih.gov/books/NBK1477/ Accessed July 26, 2018.

Bacino C. Achondroplasia. UpToDate. topic last updated: Nov 15, 2017. https://www.uptodate.com/contents/achondroplasia Accessed July 12, 2018.

• < Previous section
• Next section >

• < Previous section

Programs & Resources

• Assistance Programs
• Patient Organizations
• Registry

• < Previous section