General What's New

Part 3. Genetic Testing

This is the 3rd in an overview series on congenital differences (i.e., conditions present at birth) of the upper extremity. It might help to review Part 1 (Understanding the ‘Why’) and Part 2 (Specifics of Common Differences) before reading the following but each does stand on their own. My goal in this post is to review genetic testing from the perspective of any orthopedic surgeon but written for families. Genetic testing has dramatically changed in the last 5 years in that it has become more available to patients and can help our understanding of the ‘Why’. Insurance companies will often pay for testing (one type or another) but it can be difficult to understand because it differs from state to state based on insurance and state rules (some states require that insurance companies offer testing, others do not). Sometimes testing may also be a part of being a part of a study (i.e, research) in which case the testing is done without charge to the family. If you chose to participate in such a study, with us or with others, THANK YOU! This is how we make progress in our knowledge. If you do participate in a study, make sure you understand if the genetic information learned will be shared with you- it is not always shared.

Some basics. The genome is the name for all of our DNA- the 3 billion coding blocks. All of this DNA rests in our chromosomes- 46 (23 pairs). We do not know what all of the DNA does and we tend to focus on the coding portion of the DNA- the exome (see below)

Types of Genetic Testing

Chromosomal Testing

Chromosomal tests look for big abnormalities in our genetic code. We have 23 pairs of chromosomes in the normal state. Abnormalities of the chromosome are, in 2022, relatively straightforward to identify. These abnormalities can have major affects and include conditions like Down syndrome (3 copies of the 21st chromosome), Trisomy 18 (an extra 18th chromosome), and sex- linked chromosome abnormalities. While these conditions may have upper extremity affects, most of the conditions that I see and treat are not related to chromosomal abnormalities.

Image from NIH Genome Research Institute

Molecular Tests

Targeted Gene or Single Variant

These tests look for an abnormality (or variant) in a specific gene. The physician will be highly suspicious of a specific issue and ordering this test can confirm the problem gene. Sometimes if one family member has a known condition, this test can be used to test another family member. Examples of single variants include Sickle Cell Disease, Tay Sachs, Duchene Muscular Dystrophy, and Cystic Fibrosis. In addition, the tests that you can purchase online (23 and Me, etc) typically test a number of known genes for abnormalities.

Gene Panel

Gene panels look for variants in more than one gene. For our field of upper extremity conditions, this is likely the most common type of testing. Gene panels may be ordered by physicians, typically geneticists after a consultation. This test can serve to confirm a suspected genetic abnormality based on what we already know about the patient. These panels test for specific abnormalities in a number of genes, typically testing 10-75 known genes. Identifying the abnormality can be helpful but if the test comes back negative, it does not mean that there is not a gene abnormality- just not one we know/ one that was tested. These tests will not expand the knowledge of the medical community or find new genes that may cause conditions but can be really helpful for a family’s understanding.

Whole Exome Testing

Next is the whole exome test. The exome is the part of the DNA that is known to code and has been the focus of much of our assessment. The whole exome sequencing assess this protein-coding region of the genome. It includes less than 2% of the total 3 billion base- pair genome, but has about 85% of the known disease-causing genetic variants. Therefore, a complete assessment of the exome can be very helpful and is much less costly when compared to the whole genome testing.

Whole Genome Testing

Whole genome testing literally assesses our entire genetic code- 3 billion base pairs. It assess the exome but also the intron (the non- coding areas). We know that the intron areas matter and are likely the cause of certain conditions. Therefore, continuing to map the introns will be helpful to best understand all conditions and to understand complicated processes like limb development.

Results of Genetic Testing

The type of test affects the reporting of results. Chromosome tests and gene panels are typically positive or negative. Whole exome and whole genome testing can identify a variant which has been identified previously as a problem, can be negative for significant findings, or can identify a variant of unknown significance (VUS). These variants of unknown significance are important as they have the potential to expand our knowledge of the genetic code and of limb formation. But, if a VUS is identified, further work is needed to better understand its importance and role.


Genetic testing has progressed so much in the last 10 years. We learn so much each year about our genetic code, about limb formation, and about abnormalities (variants) that lead to limb malformations. I hope this simple overview provides helpful information. Ultimately, it will be the geneticists who help our families identify the best test to answer questions about limb malformations.

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