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 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 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.
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 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. The legs are bowed (genu varum).
- 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 timetable followed by achondroplastic children.
- Intelligence is generally normal in patients with achondroplasia. Enlargement of the brain (megalencephaly) is common and normal with achondroplasia.
In normal circumstances, FGFR3 (Fibroblast growth factor receptor 3) has a negative regulatory effect on bone growth. In achondroplasia, the mutated form of the receptor is constitutively active and this leads to severely shortened bones.
People with achondroplasia have one normal copy of the fibroblast growth factor receptor 3 gene and one mutant copy. Two copies of the mutant gene are invariably fatal before or shortly after birth. Only one copy of the gene has to be present for the disorder to occur. Therefore, a person with achondroplasia has a 50% chance of passing on the gene to his or her offspring, meaning that there will be a 50% chance that each child will have achondroplasia.
Since it is fatal to have two copies (homozygous), if two people with achondroplasia have a child, there is a 25% chance of the child dying shortly after birth, a 50% chance the child will have achondroplasia, and a 25% chance the child will have an average phenotype. People with achondroplasia can be born to parents that do not have the condition. This is the result of a new mutation.
New gene mutations leading to achondroplasia are associated with increasing paternal age (over 35 years old). Studies have demonstrated that new gene mutations for achondroplasia are exclusively inherited from the father and occur during spermatogenesis; it is theorized that oogenesis has some regulatory mechanism that hinders the mutation from originally occurring in females (although females are still readily able to inherit and pass on the mutant allele).
More than 99% of achondroplasia is caused by two different mutations in the fibroblast growth factor receptor 3 (FGFR3). In about 98% of cases, a G to A point mutation at nucleotide 1138 of the FGFR3 gene causes a glycine to arginine substitution (Bellus et al. 1995, Shiang et al. 1994, Rousseau et al. 1996). About 1% of cases are caused by a G to C point mutation at nucleotide 1138.
There are two other syndromes with a genetic basis similar to achondroplasia: hypochondroplasia and thanatophoric dysplasia.
At present, there is no known treatment for achondroplasia, even though the cause of the mutation in the growth factor receptor has been found. Therapies and diagnostic methodologies are likely to be looked into and developed.
Although used by those without achondroplasia to aid in growth, human growth hormone does not help people with achondroplasia. However, if desired, the controversial surgery of limb-lengthening will lengthen the legs and arms of someone with achondroplasia.
Usually, the best results appear within the first and second year of therapy. After the second year of GH therapy, beneficial bone growth decreases. Therefore, GH therapy is not a satisfactory long term treatment.
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.
- The foramen magnum (the large opening under the skull) may need to be surgically enlarged in cases of severe narrowing (stenosis) andcompression of the spinal cord.
- 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.
- 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. 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. The child with achondroplasia must not be allowed to become overweight. Adults with achondroplasia should also monitor and control their weight because excess weight aggravates back and joint problems.
- 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.