Achondroplasia FACTS Achondroplasia is a genetic disorder of bone growth.

growth. Achondroplasia is the most common cause of short stature with disproportionately short limbs. The appearance of the person with achondroplasia is characteristic. Intelligence is normal in people with achondroplasia. Complications of achondroplasia can affect the brain and the spinal cord. Achondroplasia is inherited as a dominant trait but 80% of cases are due to new mutations (neither parent has achondroplasia). Achondroplasia can be diagnosed before birth.

What is achondroplasia? Achondroplasia is a genetic (inherited) condition that results in abnormally short stature and is the most common cause of short stature with disproportionately short limbs. The average height of an adult with achondroplasia is 131 cm (52 inches, or 4 foot 4 inches) in males and 124 cm (49 inches, or 4 foot 1 inch) in females. Although bones. Achondroplasia is one of the oldest known birth defects. The frequency of achondroplasia is estimated to range from about 1 in 10,000 births in Latin America to about 12 in 77,000 in Denmark. An average figure worldwide is approximately 1 in 25,000 births. What are the characteristics of achondroplasia? Achondroplasia is a distinctive condition that usually can be noted at birth. The baby with achondroplasia has a relatively long, narrow torso (trunk) with short extremities (arms and legs) and a disproportionate shortening of the proximal (near the torso) segments of the limbs (the upper arms and thighs). There is a typically large head with prominence of the forehead (frontal bossing), underdevelopment (hypoplasia) of the midface with cheekbones that lack prominence, and a low nasal bridge with narrow nasal passages. The baby's fingers appear short and the ringer and middle fingers may diverge, giving the hand a trident (three-pronged) appearance. Most joints can extend more than normal. For example, the knees can hyperextend beyond the normal stopping point. Not all joints are lax in this way. To the contrary, extension and rotation of the elbow are abnormally limited. Hip extension also tends to be limited. At birth there is often prominence of the mid-to-lower back with a small gibbus (a hump). With walking, the hump goes away and a pronounced sway (lordosis) of the lumbar region (the lower back) becomes apparent. The lumbar lordosis is persistent into adulthood. The legs are bowed (genu varum). achondroplasia literally means "without cartilage formation," the defect in achondroplasia is not in forming cartilage but in converting it to bone, particularly in the long

The baby exhibits some decrease in muscle tone (hypotonia). Because of the large head, especially compared to rest of the body, and the decreased muscle tone, the child with achondroplasia will run behind "schedule" in reaching the usual motor developmental milestones. The schedule to which an achondroplastic child's development should be compared is not that for all children in the general population, but rather the growth charts and timetable followed by children with achondroplasia.

Intelligence is generally normal in patients with achondroplasia. Enlargement of the brain (megalencephaly) is common and normal with achondroplasia.

How is achondroplasia diagnosed? The diagnosis of achondroplasia can be based on the typical physical features, the hallmarks of achondroplasia, evident at birth. Characteristic features are also seen by radiology (X-ray), ultrasound, and other imaging techniques. With ultrasound imaging, the diagnosis can sometimes be strongly suspected before birth. The molecular diagnosis of achondroplasia before birth is possible if there is suspicion of the diagnosis or an increased risk (such as when a parent is affected by achondroplasia). In families in which both parents have achondroplasia, prenatal diagnosis may be particularly useful, the aim being to distinguish fatal homozygous achondroplasia (with two copies of the defective gene) from heterozygous achondroplasia (with one copy of the achondroplasia gene) from normal. Diagnosis before birth is accomplished by examining cells obtained by chorionic villus sampling (CVS) oramniocentesis. What can be done for patients with achondroplasia? Children and adults with achondroplasia can lead normal lives provided they receive attentive, informed care by their physicians and parents. Considerations in monitoring children with achondroplasia include careful measurements of growth (length/height and weight) and head circumference using curves specially standardized for those with achondroplasia. Knowledgeable pediatric care and periodic orthopedic and neurologic examinations are critical. When special problems complicate achondroplasia, prompt and expert intervention is important. For example: The foramen magnum (the large opening under the skull) may need to be surgically enlarged in cases of severe narrowing (stenosis) and compression of the spinal cord. When this opening is too narrow, the blood vessels and nerves are compressed, which can lead to centralapnea (loss of breathing control). This is responsible for the risk ofsudden death in infants with achondroplasia. The risk of sudden death for infants with achondroplasia is 2-5%. The back of patients with achondroplasia can develop a marked sway (lordosis) to the lower back while abnormalities in the mid-back may cause a small hump (kyphosis) in infancy and compression of the spinal cord in adolescence. The spinal cord compression can require surgery to decompress it. Spinal stenosis is the most common medical complication of achondroplasia seen in adulthood. Orthopedic procedures may be performed for lengthening of the limb bones and correction of bowed legs (usually after full growth has been achieved).

Surgery (lumbar laminectomy) is also indicated when spinal stenosis (narrowing) causes symptoms, which tends to be evident in young adults. Disproportion between the brain and the base of the skull can sometimes result

in hydrocephalus ("water on the brain") which needs to be promptly detected and treated by placement of a shunt to drain the excess fluid. The large head with achondroplasia increases the chance of bleeding within the baby's head during vaginal delivery. This should be taken into account in planning the birth and postnatal care, and Cesarean delivery may be recommended for a fetus with achondroplasia. The brainstem (which contains a center for controlling respiration) may be compressed in achondroplasia and contribute to abnormal breathing. Pregnant women with achondroplasia should have their babies delivered by cesarean section, due to their characteristically small pelvis, and high risk of birth related trauma. Middle ear infections are frequent and can lead to mild to moderate hearing loss. Therefore, ear infections should be readily suspected and promptly and fully treated with antibiotics or ear tubes. Dental crowding is also common. Teeth should be straightened and, if necessary, removed to alleviate this problem. Control of obesity is essential, and obesity can be a significant problem in people with achondroplasia. The excessive weight gain usually occurs during childhood. When obesity is present, the back and joint problems that are characteristic of this condition worsen in severity. The child with achondroplasia must not be allowed to become overweight. Adults with achondroplasia should also monitor and control their weight. Treatment with human growth hormone, which is still considered experimental, has been preliminarily reported to increase the growth rate after treatment, but studies have not yet demonstrated that adult height is increased by this treatment.