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.
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.
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.
- Shortened arms and legs, with the upper arms and thighs more affected than the forearms and lower legs.
- Large head size with a prominent forehead and a flattened nasal bridge.
- Crowded or misaligned teeth.
The following are the most common symptoms of achondroplasia; however, each child may experience the condition differently:
- Shortened arms and legs, with the upper arms and thighs more affected than the forearms and lower legs
- Large head size with a prominent forehead and a flattened nasal bridge
- Crowded or misaligned teeth
- Curved lower spine, a condition also called lordosis (or sway-back) which may lead to kyphosis or the development of a small hump near the shoulders that usually goes away after the child begins walking
- Small vertebral canals that may lead to spinal cord compression in adolescence
- Bowed lower legs
- Flat feet that are short and broad
- Extra space between the middle and ring fingers (also called a trident hand)
- Poor muscle tone and loose joints
- Frequent middle ear infections that may lead to hearing loss
- Delayed developmental milestones — for instance, walking may occur between 18 to 24 months of age instead of around 12 months
The symptoms of achondroplasia may resemble other problems or medical conditions. Always consult a physician for a diagnosis.
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
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.
FAQs
References
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