Achondroplasia
Achondroplasia is a form of short-limbed dwarfism. The word achondroplasia literally means “without cartilage formation.” Cartilage is a tough but flexible tissue that makes up much of the skeleton during early development. However, in achondroplasia, the problem is not in forming cartilage but in converting it to bone (ossification), particularly in the long bones of the arms and legs.
Characteristics
All individuals with achondroplasia have short stature. The average height of an adult male with achondroplasia is 131 centimeters (4 feet, 4 inches), and the average height for adult females is 124 centimeters (4 feet, 1 inch). Characteristic features of achondroplasia include an average-size trunk, short arms and legs with particularly short upper arms and thighs, limited range of motion at the elbows, and an enlarged head (macrocephaly) with a prominent forehead. Fingers are typically short and the ring finger and middle finger may diverge, giving the hand a three-pronged (trident) appearance. People with achondroplasia are generally of normal intelligence.
Causes
Achondroplasia is inherited as a dominant trait, which means one copy of the altered gene in each cell is sufficient to cause the disorder. About 80% of people with achondroplasia have average-size parents, these cases result from new mutations in the FGFR3 gene. Mutations in the FGFR3 gene cause achondroplasia. The FGFR3 gene provides instructions for making a protein that is involved in the development and maintenance of bone and brain tissue. Two specific mutations in the FGFR3 gene are responsible for almost all cases of achondroplasia. Researchers believe that these mutations cause the FGFR3 protein to be overly active, which interferes with skeletal development and leads to the disturbances in bone growth.
In the remaining cases, people with achondroplasia have inherited an altered FGFR3 gene from one or two affected parents. Individuals who inherit two altered copies (double dominance) of this gene typically have a severe form of achondroplasia that can result in extreme cases sometimes incompatible with life.
Diagnosis
Achondroplasia can be diagnosed in utero with an ultrasound or amniocentesis. After birth, characteristic features are confirmed by x-ray. If there is uncertainty, the identification of the genetic variant of the FGFR3 gene by molecular genetic testing can be used to establish the diagnosis.
Management
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.
Foramen Magnum Stenosis
Predictors of the need for suboccipital decompression require evaluation by a medical professional. Indication of symptomatic compression requires urgent referral to a neurosurgeon.
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).
Ear Infections
Due to deformity of the middle and inner ear… Ear tubes may be needed until the age of seven or eight to manage frequent middle ear infections and prevent potential hearing loss.
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 requires referral to an orthopedist. However, asymptomatic bowing does not usually warrant surgical correction.
Spinal Deformity
Early in life, infants and toddlers can develop curvature of the middle spine (kyphosis) and of the lower spine (lordosis). Preventive measures include unsupported sitting in the first 12-18 months of life. Bracing or surgery may be necessary, depending on the degree of severity and/or if preventive measures are unsuccessful.
Spinal Stenosis
Spinal stenosis, a narrowing of the spinal canal putting pressure on the spinal cord causing inherent pain, weakness and eventual bladder and bowel dysfunction, is the most common complaint and reason for disability in both children and adults. It is preventable and treatable.
Limb Lengthening
Limb lengthening is a personal decision to be made by the individual with support from their family. Anyone interested in lengthening should ensure they elect to have it done at a specialized center with extensive experience. Long bone lengthening and/or deformity correction of the upper and lower extremities can be done safely and reliably with impressive results. (link the two centers who are experts)
Drug Therapy
In 2021, VOXZOGO, BioMarin’s new drug therapy, was approved for children five years of age and older with achondroplasia whose growth plates are still open. As research continues and more drug applications are in the pipeline for achondroplasia, we are in touch with the companies and up to date on the latest advancements. Our hope for these new therapies is that they will help lessen the overall complications in addition to increasing an individual’s height. (link clinical trial information)
Support and Resources
Community- Join our community of individuals, families, and medical professionals who understand and support those living with Achondroplasia.
Educational Materials- Access a wealth of educational resources, including articles, videos, and guides to help you navigate life with Achondroplasia.
MAGIC Foundation Events- Stay updated on upcoming events, conferences, and support groups near you.
