What is Achondroplasia?
Achondroplasia is a genetic (inherited) condition that results in abnormally short stature. All persons with achondroplasia are little people. The average height of an adult with achondroplasia is 131 cm (52 inches, or 4 foot 4) in males and 124 cm (49 inches, or 4 foot 1) in females.
Achondroplasia is the most common cause of short stature with disproportionately short limbs.
Achondroplasia is a disorder of bone growth. Although achondroplasia literally means "without cartilage formation," the problem 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 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 entirely normal in patients with achondroplasia. Enlargement of the brain (megalencephaly) is common and normal with achondroplasia.
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 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 entirely normal in patients with achondroplasia. Enlargement of the brain (megalencephaly) is common and normal with achondroplasia.
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, the diagnosis can sometimes be strongly suspected before birth.
The molecular diagnosis of achondroplasia before birth is feasible. The limited number of DNA changes responsible for achondroplasia and the ease with which they can be detected provide the basis for a simple method for prenatal diagnosis. In families in which both parents have achondroplasia, prenatal diagnosis may be particularly useful, the aim being to distinguish fatal homozygous achondroplasia 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) or amniocentesis.
The molecular diagnosis of achondroplasia before birth is feasible. The limited number of DNA changes responsible for achondroplasia and the ease with which they can be detected provide the basis for a simple method for prenatal diagnosis. In families in which both parents have achondroplasia, prenatal diagnosis may be particularly useful, the aim being to distinguish fatal homozygous achondroplasia 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) or amniocentesis.
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 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) should be surgically enlarged in cases of severe narrowing (stenosis) and compression 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 required 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.
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 birth.
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.
Achondroplasia is inherited as an autosomal dominant trait whereby only a single copy of the abnormal gene is required to cause achondroplasia. The gene for achondroplasia is fully penetrant, meaning that everyone who possesses it has achondroplasia. No one with the gene escapes achondroplasia. However, there is some variation in expression of the gene, meaning that children with achondroplasia are not carbon copies of each other, although they may look alike to the untutored eye.
In only about an eighth of cases is the gene inherited from a parent who has achondroplasia. Conversely, about seven-eighths of cases are due to a new mutation (a new change in the gene). This means that most cases of achondroplasia occur sporadically (out of the blue) and are the result of a new mutation in a sperm or ovum of one of the normal- appearing parents. The chance of a new mutation rises with the age of the father. As early as 1912 it was noted that sporadic (new) cases were more often last-born than first-born children. This fits with the fact that the chance of an achondroplastic birth has been shown to increase with paternal age (age of the father).
What if someone with achondroplasia has children?
Although most children with achondroplasia do not have an achondroplastic parent but have a new mutant gene for achondroplasia, they can still transmit the gene to their children. No matter whether a person with achondroplasia carries a new or an "old" gene, the risk for passing that gene down to a child is 50%. It is 50% with each pregnancy, irrespective of the outcome of prior pregnancies. It is like flipping a coin each time.
What if two people with achondroplasia have children?
People with achondroplasia sometimes have children together. If so, each parent has a 50:50 chance of passing on the gene. Thus, with each conception, there is a 25% chance for an average-size child, a 50% chance for a child (like them) with achondroplasia and a 25% chance for a conception with two achondroplasia genes. The combined presence of two genes for achondroplasia (called homozygous achondroplasia) causes a grievous skeletal disorder that leads to early death from breathing failure due to constriction by a tiny chest cage and neurologic problems from hydrocephalus.
Homozygous achondroplasia, although fatal, has led to insights into other medical conditions. For example, similarities were noticed between homozygous achondroplasia and a condition called thanatophoric dwarfism. It was proposed that the two disorders might be due to different mutations in the same gene and this has proven to be the case. Another skeletal disorder called hypochondroplasia has also turned out to be due to yet another mutation (change) in the same gene. Achondroplasia, thanatophoric dwarfism, and hypochondroplasia are thus due to mutational changes at the same gene locus.
What gene causes achondroplasia?
The locus of the gene for achondroplasia (which is also the locus of the genes for thanatophoric dwarfism and hypochondroplasia) has been mapped. Linkage studies were done of families with achondroplasia tracing the transmission of DNA markers whose chromosomal locations were known. These studies revealed that the gene for achondroplasia was on the short (p) arm of chromosome 4 in chromosome band 4p16.3.
Once the gene for achondroplasia was isolated to the region 4p16.3, genes in the region that might logically be the gene for achondroplasia were examined. It was discovered that mutations causing achondroplasia were synonymous with changes in the gene for fibroblast growth factor receptor-3 (FGFR3). The exact FGFR3 mutation in most persons with achondroplasia is the same. It is a substitution, to be precise, at nucleotide number 1138 in the DNA. This substitution on the DNA level results in a minute change on the protein level. There is the substitution of one amino acid for another, specifically an arginine for a glycine at position number 380 of the protein in the transmembrane domain of FGFR3. This change in the structure of this protein is sufficient to impair the function of the receptor. Genetic research on achondroplasia has yielded this information since 1994. How this minute genetic change produces the features of achondroplasia is a matter for current research.
Achondroplasia is a genetic disorder of bone 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 entirely normal in people with achondroplasia. Complications of achondroplasia can affect the brain and the spinal cord. The parents of children with achondroplasia are usually normal. Achondroplasia is inherited as a dominant trait. Achondroplasia can be diagnosed before birth.
Information By Medicinenet.com
