Campomelic dysplasia is a congenital (at birth) disorder that affects the development of various body parts including the skeleton and the reproductive system. It is a life-threatening disorder during the newborn period. This disorder is given the name ‘campomelic dysplasia’ after the word ‘campomelic’ which is Greek meaning ‘bent limb.’ Individuals who are affected by this disorder are born with developmental issues such as bowing bones of the legs or occasionally bowing bones of the arms. Characteristic skin dimples may form over the bowed bone, particularly on the individual’s lower legs. Individuals who have this disorder tend to have dislocated hips, unusually short legs, and underdeveloped shoulder blades. They also have 11 pairs of ribs rather than the usual 12.
Sometimes, individuals may have features of the disorder, however, their limbs may not be bowed. When that is the case, then it is said to be acampomelic campomelic dysplasia. Many people who have the disorder have unclear female or male external genitalia, also referred to as ambiguous genitalia. About 75 percent of the individuals affected by the disorder and who have normal male chromosome patterns of 46,XY tend to have ambiguous genitalia or usual female genitalia. The reproductive organs might not relate with the individual’s external genitalia meaning they may be male referring to testes, they may be female referring to ovaries, or they may be a combination of ovaries and testes. That’s why it is, for example, advisable by doctors to reassign the male sex individuals having female genitalia as females.
Only a few individuals having campomelic dysplasia thrive past infancy. With time, as the individuals age, there may be some abnormalities that will develop such as an atypical curvature of their spine, a condition known as scoliosis. Other spine related abnormalities may also begin to show up and they tend to compress the spinal cord of the individual. People who have the disorder will have other problems like hearing loss and short stature. The prevalence of this disorder is not well known, but it is estimated to range from 1 in every 40,000 to 200,000 births.
Causes of Campomelic Dysplasia
Campomelia dysplasia is caused by mutations occurring in the SOX9 gene. This gene is responsible for providing instructions for the body to make a protein that is used in the formation of different organs and tissues at time of embryonic development. It is the SOX9 protein that helps with regulation of activities of other genes particularly the ones that are indicated in the development of skeleton and the reproductive organs.
When there is mutation of the SOX9 gene, it means that there is limitation in the production of the SOX9 protein. Sometimes, the protein may be produced but it has impaired function. It is estimated that about 5% of campomelic dysplasia cases occur due to chromosome abnormalities occurring near the SOX9 gene. With these cases, they tend to be milder compared to the cases arising from mutations occurring within the SOX9 gene itself.
With the chromosomal abnormalities, they disrupt the DNA regions that help to regulate the function and activity of the SOX9 gene. The various genetic changes affect the SOX9 protein making it to be unable to properly control those genes said to be responsible in initiating the normal development of embryonic skeleton and reproductive system among other parts of a person’s body. It is the abnormal development of the various structures that causes the signs and symptoms associated with campomelic dysplasia.
An important thing to mention here is that the mutations either occur near or in the SOX9 gene. When the mutations occur near the gene, the symptoms of campomelic dysplasia are milder than when the mutations occur in the gene itself.
How Campomelic Dysplasia Is Acquired
Campomelic dysplasia is actually inherited through an autosomal dominant pattern. This means that a copy of the mutated or altered gene within each cell is sufficient enough to cause this disorder. When a person is said to have an autosomal dominant gene related to a disorder, it means that with each pregnancy, there is at least a 50 percent or 1 in 2 chances for the embryo to acquire the genetic disorder. There is also a 50 percent chance of the embryo not acquiring the disorder. Most cases of this disorder result from new SOX9 gene mutations or alterations and happen in individuals who may not have any history of the disorder in their family.
It is rare for people having campomelic dysplasia to inherit a chromosome anomaly like translocation, deletion, or inversion in or near the SOX9 gene from say a parent who did or did not show symptoms and signs of the disorder. Because a majority of the person having campomelic dysplasia get it from a de novo (new) mutation, you will find that parents of these individuals don’t usually have signs and symptoms signifying the genetic disorder.
That said, it is important to note that some few adults have actually been diagnosed with the disorder after having a birth of a child who is affected or after diagnosing the fetus with the disorder during pregnancy.
Signs and Symptoms of Campomelic Dysplasia
An individual with campomelic dysplasia will have symptoms such as:
- Dislocated hips
- Large heard when compared to the size of the body
- Short and bowed or curved long bones of the individual’s legs, sometimes, the arms may also be bowed. There may occur skin dimples that arise due to the curving or bowed bents particular on the lower limbs. These symptoms are congenital – meaning they are present at birth.
- Underdeveloped shoulder blades
- Anomaly rotated feet or club feet
- 11 pairs of ribs and not the usual 12 pairs
- Facial features like prominent eyes, small chin, and flat face
- External genitalia that aren’t well pronounced, they don’t clearly look like female or male genitalia. There may also be normal female genitalia having usual male chromosome pattern of 46, XY in say 75 percent of the cases. The internal reproductive organs could be noncorresponding with the individual’s external genitalia. The persons who have this disorder have ovaries, testes, or a combination.
- A person may have Pierre-Robin sequence involving an opening that occurs in the mouth’s roof (a cleft palate). The individual may also have a tongue located further back than normal, a condition known as glossoptosis. Also, the person may have a small lower jaw, a condition known as micrognathia.
- It is also likely that a person will have weakened cartilage involving the upper respiratory tract that partly blocks the airway. This may cause severe breathing difficulties, something that leads to poor survival of babies or infants having campomelic dysplasia.
Respiratory distress occurring due to underdeveloped ribcage is cited as the most serious symptom of this disorder. With underdeveloped ribcage, it creates insufficient space for the lungs to grow properly thus bringing about breathing difficulties.
Diagnosis of Campomelic Dysplasia
There are two ways through which campomelic dysplasia can be diagnosed:
- First, a doctor looks at the symptoms and features a person expresses
- Secondly, the doctor orders for genetic testing.
A detailed physical examination can be done by the doctor. The doctor takes X-rays to examine the bone. Also the doctor will look for features such as presence of 11 pairs of ribs instead of having12, and a baby having a large head.
There are quite few genetic tests that can help with diagnosis of the disorder. Tests known as gene sequencing as well as gene duplication or deletion analysis are commonly used. Gene sequencing looks for mutations while gene duplication or deletion analysis checks for bigger pieces of genetic information such as missing or extra parts in the gene.
Prenatally, it is possible that diagnosis can be made. Sometimes, the bowed or curved limbs of babies in the womb may be detected using an ultrasound. If there is a member of the family who has the disorder or when the doctor sees the curved limbs through ultrasound, then genetic tests may be ordered to check the baby’s DNA.
Because samples for testing have to be taken from the baby in the womb, specialized procedures for collecting the samples are applied. Amniocentesis and chorionic villus sampling (CVS) are invasive procedures that are used to collect the samples. But these procedures may present some small risk of miscarriage.
In CVS, a small piece of the fetus placenta is removed and send to the lab for genetic testing. This procedure may be conducted around the 10th to 12th week of gestation. With amniocentesis, it collects the amniotic fluid and the sample is taken to a lab facility for genetic testing. This test can be conducted beginning from the 15th week of gestation.
Treatment of Campomelic Dysplasia
Treatment is aimed at helping the patient deal with the symptoms. Depending on what symptoms the patient have, appropriate treatment approaches can be adopted. Because this is a genetic disorder, there isn’t a way to reverse it but to deal with the symptoms. In treating the respiratory problems, physical or mechanical breathing assistance may be applied, for example, positive-end expiratory pressure (PEEP).
In the case of serious bone deformities then surgery and orthopedic medical care may be used to alleviate the problems. Through orthopedic care, the bowed tibia can actually straighten. It would be recommended that doctors reassign the male sex individual having female genitalia as a female.
Another approach that may help is genetic counseling, it could benefit the patient and his or her family. Other treatment options are symptomatic and supportive. For example, in 2004, the FDA approved the Vertical Expandable Prosthetic Titanium Rib (VEPTR) for the treatment of pediatric patients having thoracic insufficiency syndrome (TIS). Patients with campomelic dysplasia may benefit from VEPTR because it helps with treatment of congenital conditions that present with deformities of body parts like the spine, chest, and ribs. VEPTR is pretty and expandable device that is implanted in the body to help straighten the spine or separate the ribs to allow the lungs to grow. Its length can be adjusted as an individual grows. VEPTR was developed in San Antonio at the University of Texas Health Science Center.
