Genetic Testing FAQ


What should I know about a muscle biopsy?

It is good medicine to see the patient before even scheduling a biopsy, not just the day before the actual biopsy. Biopsies are invasive, costly, and can be very challenging to some so care should be taken if a biopsy is even warranted. Often physicians without an intimate knowledge of neuromuscular disease will assume that a patient requires a muscle biopsy for further evaluation of his/her problems. They are not aware of all the new testing that can provide better results from a simple blood draw or buccal swab. On a number of occasions, Dr. Kendall has been asked to see someone with suspected mitochondrial disease to arrange for a muscle biopsy only to discover on evaluation that the patient actually had another muscle disease, such as Pompe disease, a treatable disorder easily diagnosed with a blood sample. As such, undergoing an evaluation with someone with expertise in this arena is critical.

If for some reason a biopsy is still needed, VMP will assist in making the arrangements for your biopsy through our outpatient partners and local hospitals (see our patient testimonial regarding her experience). Our partners and hospitals will work directly with you and your insurance while we will diligently work on your behalf to ensure the proper testing is done without the surprise of add -on testing. Once the evaluation is complete, we will review all of the results and provide you with a written interpretation of the testing and the implications for your child/you and your family... and we will always be available for any follow up if necessary.

Regardless of whom you pick as your physician, a few things to know about a muscle biopsy to confirm suspected mitochondrial disease.

In the event it is truly felt that a muscle biopsy is required please keep in mind that not all labs are the same. Some labs will do, in our opinion, many unnecessary muscle tests as part of a biopsy evaluation resulting in prohibitive costs to you and your insurance company.

  • While your insurance may pre approve the testing, be aware that some labs may add on testing after approval that your insurance will deny making you financially responsible for these additional add on tests. All of this may be done without your knowledge. Please know the labs we work with do not have this practice and we work hard to have the appropriate testing done, and that is all. We have no financial incentive to increase the cost of testing. 
  • Always remember that even though an insurance carrier may cover the costs with little or no out of pocket expense to you now, there are lifetime caps on insurance coverage and unnecessary testing and charges to a healthcare insurance provider may prevent necessary testing or coverage down the road. Once again we work hard to have the appropriate testing done and that is all.

There is also ongoing controversy over fresh vs. frozen muscle biopsies. Some labs will claim that only a fresh biopsy is reliable although they will do the same testing on frozen tissue if requested to do so. The cost for a fresh biopsy is typically far greater than a frozen sample and will often require travel from home and other out of pocket expenses. Although freezing of muscle tissue can affect the integrity of complex I in the mitochondrial energy pathway system, this can be avoided by proper collection and handling of the sample. Review of data from fresh vs. frozen biopsies has indicated that with proper collection and sample processing, the results are the same making neither approach better than the other.

As more and more gene tests responsible for mitochondrial disease become commercially available, many metabolic and mitochondrial physicians are now moving away from invasive biopsies looking towards these simple blood studies reducing costs and discomfort to patients. We are actively involved in bringing these new solutions to bare on behalf of our patients.

What is next gen sequencing?

The high demand for low-cost sequencing has driven the development of high-throughput sequencing (or next-generation sequencing) technologies that parallelize the sequencing process, producing thousands or millions of sequences at once. High-throughput sequencing technologies are intended to lower the cost of DNA sequencing beyond what is possible with standard dye-terminator methods. In ultra-high-throughput sequencing as many as 500,000 sequencing-by-synthesis operations may be run in parallel.

What is exome sequencing?

Exome sequencing (also known as targeted exome capture) is an efficient strategy to selectively sequence the coding regions of the genome as a cheaper but still effective alternative to whole genome sequencing. Exons are short, functionally important sequences of DNA which represent the regions in genes that are translated into protein and the untranslated region (UTR) flanking them. UTRs are usually not included in exome studies. In the human genome there are about 180,000 exons: these constitute about 1% of the human genome, which translates to about 30 megabases (Mb) in length. It is estimated that the protein coding regions of the human genome constitute about 85% of the disease-causing mutations.

The robust approach to sequencing the complete coding region (exome) has the potential to be clinically relevant in genetic diagnosis due to current understanding of functional consequences in sequence variation. The goal of this approach is to identify the functional variation that is responsible for both mendelian and common diseases without the high costs associated with whole-genome sequencing while maintaining high coverage in sequence depth.

Whole exome sequencing is a brute-force approach that involves using modern day sequencing technology and DNA sequence assembly tools to piece together all coding portions of the genome. The sequence is then compared to a reference genome and any differences are noted. After filtering out all known benign polymorphisms, synonymous changes, and intronic changes (that do not affect splice sites), only potentially pathogenic variants will be left. This technique can be combined with other techniques to further exclude potentially pathogenic variants should more than one be identified.

What are the uses of a genetic test?

As we specialize in Pediatrics and Adults, clinically applicable genetic tests may be used for:

  • Diagnostic testing
  • Clinical testing 
  • Predictive testing 
  • Carrier testing

Research tests generally do not give clinically applicable results.

What is a Genetic test?

A genetic test is the analysis of human DNA, RNA, chromosomes, proteins, or certain metabolites in order to detect alterations related to a heritable disorder. This can be accomplished by directly examining the DNA or RNA that makes up a gene (direct testing), looking at markers co-inherited with a disease-causing gene (linkage testing), assaying certain metabolites (biochemical testing), or examining the chromosomes (cytogenetic testing).

Although genetic testing shares some features in common with other kinds of laboratory testing, in many ways it is unique and requires special considerations.

  • Genetic testing may be used for medical management and for personal decision-making.
  • Genetic test results usually apply not only to the patient but also to other family members.
  • Genetic testing may be performed in the context of a genetics consultation and should include informed consent, test interpretation, and follow-up medical and psychosocial services as indicated.
  • Because most genetic disorders are rare, genetic testing is often done only by specialized laboratories.
  • Intense research efforts in molecular genetics result in the rapid development and availability of new genetic tests; therefore, healthcare providers need to continuously update their knowledge.
  • In order for genetic testing to yield meaningful results:
    • multiple test methodologies may be required
    • other family members may need to be tested
    • a genetics consultation may be appropriate
    • these services will entail additional costs

What is a Clinical test?

Clinical tests are those in which specimens are examined and results reported to the provider or patient for the purpose of diagnosis, prevention or treatment in the care of individual patients.

  • United States laboratories performing clinical tests must be CLIA approved.
  • There is a charge for clinical tests; cost varies by complexity.
  • Test results are reported in writing.

The time between specimen submission and reporting of results varies between laboratories and may be based in part on the complexity of the testing.

What is Diagnostic testing?

Diagnostic testing is used to confirm or rule out a known or suspected genetic disorder in a symptomatic individual.

  • DNA testing may yield diagnostic information at a lower cost and with less risk than other procedures.
  • Diagnostic testing is appropriate in symptomatic individuals of any age.
  • Confirming a diagnosis may alter medical management for the individual.
  • Diagnostic testing of an individual may have reproductive or psychosocial implications for other family members as well.
  • Establishing a diagnosis may require more than one type of genetic test.

DNA testing may not always be the best way to establish a clinical diagnosis.

What is Predictive testing?

Predictive testing is offered to asymptomatic individuals with a family history of a genetic disorder. Predictive testing is of two types: presymptomatic (eventual development of symptoms is certain when the gene mutation is present, e.g., Huntington disease) and predispositional (eventual development of symptoms is likely but not certain when the gene mutation is present).

  • Predictive testing is MEDICALLY INDICATED if early diagnosis allows interventions which reduce morbidity or mortality.
  • Even in the absence of medical indications, predictive testing can influence life planning decisions.
  • Because predictive testing can have psychological ramifications, careful patient assessment, counseling, and follow-up are important.
  • Many laboratories will not proceed with predictive testing without proof of informed consent and genetic counseling.
  • Identification of the specific gene mutation in an affected relative or establishment of linkage within the family should precede predictive testing.

Predictive testing of asymptomatic children at risk for adult-onset disorders is strongly discouraged when no medical intervention is available.

What is Carrier testing?

Carrier testing is performed to identify individuals who have a gene mutation for a disorder inherited in an autosomal recessive or X-linked recessive manner. Carriers usually do not themselves have symptoms related to the gene mutation. Carrier testing is offered to individuals who have family members with a genetic condition, family members of an identified carrier, and individuals in ethnic or racial groups known to have a higher carrier rate for a particular condition.

  • Identifying carriers allows reproductive choices.
  • Genetic counseling and education should accompany carrier testing because of the potential for personal and social concerns.
  • Molecular genetic testing of an affected family member may be required to determine the disease-causing mutation(s) present in the family.
  • In some situations, DNA testing may not be the primary way of determining carrier status.

Carrier testing can improve risk assessment for members of racial and ethnic groups more likely to be carriers for certain genetic conditions.


What is a Research test?

Research tests are those in which specimens are examined for the purpose of understanding a condition better, or developing a clinical test.

  • Laboratories performing research testing are not subject to CLIA regulation.
  • The cost of research testing is generally covered by the researcher.
  • Test results are generally not given to patients or their providers.
  • Rarely, a research laboratory will, at the patient's request, share potentially useful findings with a clinical laboratory so the patient's test results can be confirmed and a formal report issued.
  • Requests for participation in research may be denied, at the laboratory's discretion, if the laboratory has sufficient samples or the family does not fit the research project goals.

Some tests listed as "Research" may fall into the "Investigational" category.

What is an Investigational test?

Investigational tests are deemed to be of value but not yet scientifically valid or generally accepted by the medical community as accurate and useful.

  • Test results may or may not be shared, and it may be a long time before results are available.
  • If test results are shared with the provider or patient, the laboratory must be CLIA approved.
  • There may or may not be a cost for testing.
The category "Investigational," which is used by some laboratories, is too loosely defined to be very helpful.


What is Newborn Screening?

Newborn screening identifies individuals who have an increased chance of having a specific genetic disorder so that treatment can be started as soon as possible.

  • Newborn screening programs are usually legally mandated and vary from state to state.
  • Newborn screening is performed routinely at birth, unless specifically refused by the parents in writing.
  • Screening tests are not designed to be diagnostic, but to identify individuals who may be candidates for further diagnostic tests.
  • Many parents do not realize that newborn screening has been done (or which tests were included), even if they signed a consent form when their child was born.

Education is necessary with positive screening results in order to avoid misunderstandings, anxiety and discrimination.