Pseudoachondroplasia Health Article

Demographics

The exact prevalence of pseudoachondroplasia is unknown, but it is estimated to occur in about one in 30,000 individuals. Pseudoachondroplasia affects males and females in equal numbers. Most individuals with pseudoachondroplasia are born to parents with average stature. This is due to a new mutation that occurs on the COMP gene of the child with pseudoachondroplasia.

Signs and symptoms

Individuals with pseudoachondroplasia have disproportionate short stature, normal-sized heads, limb differences, and rhizomelic shortening of their limbs; rhizomelic means "root limb." Rhizomelic shortening of the limbs means that those segments of a limb closest to the body (the root of the limb) are more severely affected. In individuals with pseudoachondroplasia, the upper arms are shorter than the forearms, and the upper leg (thigh) is shorter than the lower leg.

In addition to shortened limbs, individuals with pseudoachondroplasia have other characteristic limb differences. They have a limited ability to rotate and extend their elbows. They also have joint laxity, particularly of the hands, ankles, and knees. Because of this joint laxity, they can be bowed legged or knock kneed and may have in-turned toes. Their hands and feet are short and broad, as are their fingers and toes. Their fingers and other joints are hyperextensible, or very flexible.

In addition to limb differences, individuals with pseudoachondroplasia have other characteristic skeletal differences. Because of malformed vertebra and lax ligaments, individuals with pseudoachondroplasia can have spinal problems, including kyphosis (hunchback), lordosis (swayback), and scoliosis.

Individuals with pseudoachondroplasia have normal facial features and a normal-sized head. This is one of the major features that differentiate pseudoachondroplasia from achondroplasia. Individuals with pseudoachondroplasia have shortening of their long bones. The average adult height of individuals with pseudoachondroplasia ranges from 32–52 in (80–130 cm).

Diagnosis

Pseudoachondroplasia is diagnosed by a combination of physical exam, x rays, and molecular testing. The characteristic findings of short stature and rhizomelic shortening of the limbs become apparent around two years of age and become more pronounced over time. In addition to being diagnosed by physical examination, individuals with pseudoachondroplasia have some specific bone changes that can be seen on an x ray. A DNA blood test to look for mutations in the COMP gene may also help clarify the diagnosis.

Unlike other skeletal dysplasias, pseudoachondroplasia cannot be diagnosed by a prenatal ultrasound or sonogram because the characteristic changes in the bones and the growth delays do not appear until the child is two years of age.

The diagnosis of pseudoachondroplasia can be made prenatally by DNA testing if the mutation for that family has been characterized. A sample of tissue from a fetus is obtained by either chorionic villi sampling (CVS) or by amniocentesis. Chorionic villi sampling is generally done between 10 and 12 weeks of pregnancy, and amniocentesis is done between 14 and 18 weeks of pregnancy. Chorionic villi sampling involves removing a small amount of tissue from the developing placenta. The tissue in the placenta contains the same DNA as the fetus. Amniocentesis involves removing a small amount of fluid from around the fetus. This fluid contains some fetal skin cells from which DNA can be isolated. The fetal DNA is then tested to determine if it contains the mutation that is responsible for pseudoachondroplasia in that family.

Prenatal DNA testing for pseudoachondroplasia is not routinely performed in low-risk pregnancies. This type of testing is generally limited to high-risk pregnancies, such as those in which both parents have pseudoachondroplasia or one in which one parent has pseudoachondroplasia and the other parent has another autosomal dominant form of skeletal dysplasia. It is particularly helpful in determining if a fetus has received two dominant skeletal mutations. Infants who have inherited two autosomal dominant skeletal dysplasias may have very severe complications that may result in death.

DNA testing can also be performed on blood samples from children or adults. This is usually done as part of a genetic work-up to establish the exact form of skeletal dysplasia. Many skeletal dysplasias can be hard to differentiate from one another, and DNA testing can often clarify the diagnosis.