Achondroplasia

Definition

Achondroplasia is a genetic disorder that causes dwarfism (short stature). It is a disorder in which bone and cartilage do not grow normally. It is the most common cause of dwarfism.

This condition leads to patients reaching a full-grown height of less than four feet. The greatest shortening occurs in the humerus (the bone between the shoulder and the elbow) and the femur (the bone between the hip and the knee). There may also be underdevelopment of the face.

Achondroplasia is the most common form of inherited disproportionate short stature. It occurs in one in 26,000 to one in 40,000 live births.

Causes

Achondroplasia is a genetic disorder. It is caused by mutations in the FGFR3 gene. This gene prevents the growth of cartilage at the growth plate. FGFR3 encodes a protein called Fibroblast Growth Factor Receptor 3. This protein is the site of action of a major growth factor responsible for lengthening bones. When this growth factor cannot act properly due to the absence of its receptor, the growth of bones, at the growth plate's cartilage, is slowed. This leads to shorter bones, abnormally shaped bones, and shorter stature.

The gene for achondroplasia can be passed from one generation to the next. If a parent has the disorder, there is a 50% chance of passing the gene for achondroplasia to children. In most cases of achondroplasia (80%-90%), it more commonly is the result of a spontaneous mutation (a sudden genetic defect) that occurs in the developing embryo.

Risk Factors

A risk factor is something that increases your chances of getting a disease or condition. Those at risk of inheriting achondroplasia are:

• Children of a parent with achondroplasia
• Children of normal-sized parents who carry a mutated FGFR3 gene
• Advanced paternal age causing spontaneous mutations

Symptoms

Symptoms of achondroplasia include:

• Short stature, a long trunk, and shortened limbs, which are noticeable at birth
• An adult height of between 42-56 inches
• The head is large and the forehead is prominent
• Portions of the face can be underdeveloped
• At birth, the legs appear straight, but as a child begins to walk, he or she develops a knock-knee or bowed-leg deformity
• The hands and the feet appear large, but the fingers and toes are short and stubby
• Straightening of the arm at the elbow may be limited, but usually does not keep a patient from doing any specific activities
• Children may develop an excessive curve of the lower back and a waddling walking pattern
• Dental problems

Other common symptoms include:

• Weight control problems
• Bowed legs
• Middle ear infections, especially in children
  • If not treated properly, can result in hearing loss
• Dental problems (from overcrowding of teeth)
• Hydrocephalus (water on the brain)
• Neurologic and respiratory problems
• Fatigue, pain, and numbness in the:
  • Lower back
  • Spine
• Spinal compression may occur in the upper back or where the spinal cord exits from the skull in the back of the neck
  • Compression at the back of the neck may cause sleep apnea or even death if not recognized and treated early
  • MRI or CT scans can help detect these complications

The prognosis depends on the severity of the disease. Patients who have two copies of the deficient gene (ie, one from each parent, also known as homozygous) generally die a few weeks to months after birth. Those with one copy (ie, from only one parent, also known as heterozygous) have a normal life span and intelligence. However, children often take longer to develop normal motor skills. There is also an increased risk of death in the first year of life due to respiratory problems. They are usually independent in their daily life activities.

Diagnosis

Diagnosis includes:

• Clinical evaluation
• Radiographs
• Molecular genetic testing to detect a mutation in the FGFR3 gene. Such testing is 99% sensitive and is available in clinical laboratories.
• X-rays

Spinal Stenosis

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Treatment

Unfortunately, there is currently no treatment that can cure this condition. Scientists are exploring ways to create alternate growth factors which can bypass the missing receptor and lead to normal bone growth. They may offer the possibility of enhanced stature to future families who have children with achondroplasia.

Prevention

There are no steps to prevent a genetic disorder. Genetic counseling can discuss the chances your child will have achondroplasia. You may consider this counseling if you are planning on having a child and have a family history of genetic conditions.