The term skeletal dysplasia refers to a group of disorders that affect the bone and cartilage of the skeletal system during pregnancy. While rare, skeletal dysplasias are one of many conditions that we pay attention to during fetal ultrasounds. There are over 450 recognized types of skeletal dysplasias, and most likely many more that have not been identified. As a group, skeletal dysplasias account for up to 4.5 per 10,000 births and 20 per 10,000 stillbirths.
Understanding Skeletal Dysplasia
Beginning in the early stages of fetal development during pregnancy, the fetal bones and cartilage do not form properly and can have structural abnormalities. Some of the types of skeletal dysplasias are considered lethal and severe enough that abnormalities can be seen early on in pregnancy, even in the first trimester. Abnormalities that could be signs of skeletal dysplasia include anomalies of bone shape, size and density of bones, and specifically of the fetal limbs, chest, or skull. Every woman has a risk of having a pregnancy diagnosed with this disorder.
If a skeletal dysplasia is suspected early on in pregnancy, there are many options moving forward. It is important to discuss each of these options with your physician or genetic counselor. Although a very difficult and emotional decision, the pregnancy can be terminated. If choosing to move forward with the pregnancy, the pregnancy can continue to be monitored by ultrasound, to look for progression of the disorder.
If there is a desire to try and determine the cause of the skeletal dysplasia, diagnostic testing during pregnancy is an option. Chorionic Villus Sampling (CVS) can be performed between 10-12 weeks of pregnancy and involves taking a sample of the placenta. Depending on the location of the placenta in the uterus, a flexible catheter is inserted through the vagina and into the cervix, or a needle is inserted through the abdomen to take the sample of placenta. Since the placenta and fetus originate from the same source, almost always the genetics of both are the same.
Due to a CVS being an invasive procedure, there is a risk of miscarriage associated, which is approximately 1/200. An amniocentesis can be performed after 15 weeks of pregnancy and involves inserting a needle through the abdomen to withdraw a small portion of amniotic fluid, which contains some of the fetal skin cells. This procedure also is associated with a risk of miscarriage, approximately 1/300 – 1/500.
Diagnosing Skeletal Dysplasia
The purpose of performing a diagnostic procedure during pregnancy is to possibly identify the cause or origin of the skeletal dysplasia. There are many causes of skeletal dysplasia, including chromosomal abnormalities, single gene mutations, as well as environmental factors like exposure to medication or chemicals and autoimmune response. If a couple chooses to pursue a diagnostic test, the sample is collected and can be sent to a lab for analysis. Proteins and chemicals can be analyzed, in addition to genetic testing. The genetic information from the pregnancy can be obtained and analyzed to see if there is a genetic cause for the disorder. The first test that can be performed is a microarray, which analyzes the genetic instructions bundled into chromosomes. This test searches for chromosome abnormalities, including whole chromosomes that are missing or duplicated, or small pieces of chromosomes that are missing or duplicated.
The second genetic test that can be performed is a skeletal dysplasia panel, which analyzes individual genes, or much smaller portions of genetic instructions within chromosomes, that could contain an error that causes the gene to not function properly. Many different labs offer genetic testing for skeletal dysplasia panels. Some labs offer panels that have approximately 20 genes associated with this disorder others offer 100+ genes associated with its conditions. It is important to discuss with your genetic counselor the best genetic testing options and best test for your situation and pregnancy.
Skeletal Dysplasia Genetics: What are the Causes?
Sometimes, a cause can be identified that explains why the pregnancy was diagnosed with skeletal dysplasia. Often, especially in lethal cases, if a genetic cause is identified, it’s typically considered to be sporadic and not inherited. However, there are many circumstances where a cause is never identified that explains why the pregnancy was diagnosed with skeletal dysplasia. In these circumstances there are research databases specifically for skeletal dysplasia conditions to continue to research a cause as to why it happened.
If you are interested in learning more about skeletal dysplasias, have a family history of skeletal dysplasia, or currently have a pregnancy diagnosed with skeletal dysplasia and would like to discuss your options, please contact AT-GC to meet with a genetic counselor.