How FirstStepDx PLUS® Helps

If you don’t understand the genetics, you don’t understand the disease.

Only a genetic diagnosis can pinpoint which one of hundreds of known conditions may be responsible for your patient’s symptoms, which treatment is best, what the chances are of recurrence or whether there is an accompanying co-morbidity.

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Rena Vanzo MS, LCGC Licensed & Certified Genetic Counselor,
Vice President, Clinical Services, Lineagen, Inc.

Read More: Why get a genetic test when the child has already been diagnosed?

Many healthcare providers have difficulty explaining to their patients why a genetic diagnosis is important in addition to a descriptive diagnosis like developmental delay or autism spectrum disorder.

We are looking for more than just a descriptor for what's happening with the child. We want to know why that descriptor is present and why that child has developmental delay or autism.

A diagnosis is just a description, not a cause

It's almost as if a patient is asking, what's wrong with my car? Your car is broken down. That's not a detailed enough answer. A mechanic is not going to know how to fix a broken down car. They need to do a diagnosis on that car. Is the tank out of gas? Are the tires not working? Do we need a new engine?

There can be a variety of reasons why something is not working properly and until we know that specific reason, we don't know how to fix that car or in this case treat that patient. That's one analogy that has helped families understand the importance of having a specific, genetic ideology to their child's developmental delay or autism spectrum disorder.

A real-life example

There may be two children similar in age who both have low muscle tone, speech and language difficulties and developmental delay. If we performed CMA for both of those children, it would not be uncommon to find that one of those children has DiGeorge syndrome, which is also known 22q11.2 deletion syndrome.

It would also not be uncommon for a child with those descriptors to have a deletion that causes Angelman syndrome. These are both conditions that are diagnosed by the CMA but have vastly different prognosis and medical comorbidities for the child.

Very different prognoses

In the case of 22q deletion syndrome, that child should be screened for certain heart defects. Their palate may have abnormalities that are causing the speech and language issues and that individual as well as his or her parents could beat risk for certain psychiatric illnesses if they have the deletion1.

Angelman syndrome carries a high risk for seizures

In contrast, the individual with Angelman syndrome has a very high risk for seizures. And that child could benefit from an evaluation with a neurologist to get a baseline understanding of what's happening with the brain. And Angelman syndrome is most often de novo in a patient. De novo means that the deletion is new in the patient and is not carried by one of the parents.

So two children can present in very similar ways. Both can have a general diagnosis of delay or autism. But both can have very different conditions. And those children need to be treated differently. The families can also find out the facts about their child's genetic syndrome and find unique support with that genetic community.

It helps to know specifically what the problem is

There are support groups for both of these conditions and it benefits parents and other family members to have an understanding of what is happening with their child. Parents might be harboring some blame and genetic testing can really begin to help families cope with some of these issues.

1. McDonald-McGinn DM, Emanuel BS, Zackai EH. 22q11.2 Deletion Syndrome. 1999 Sep 23 [Updated 2013 Feb 28]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from:http://www.ncbi.nlm.nih.gov/books/NBK1523/

2. Dagli AI, Mueller J, Williams CA. Angelman Syndrome. 1998 Sep 15 [Updated 2015 May 14]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.Available from: http://www.ncbi.nlm.nih.gov/books/NBK1144/

Rena Vanzo MS, LCGC Licensed & Certified Genetic Counselor,
Vice President, Clinical Services, Lineagen, Inc.

Read More: Effective therapies require a genetic diagnosis

In the past when a child was diagnosed with developmental delay or autism spectrum disorder, little was available to those families by way of therapy, treatments or support services.

That's not true these days. There are many opportunities available to these families especially with the advent of personalized medicine. Many drug companies and scientific researchers have clinical trials that are available where drugs are now being developed that actually address the biochemical deficiency in certain genetic conditions.

These drug treatments may have a significant impact on that child's ability to interact with his or her environment, on his or her behavior and there's much hope for families.

Critical to understand the underlying condition before prescribing a treatment

But these opportunities may not be available if we don't know the underlying condition for a child.

It is important for doctors to take the initiative to provide a genetic diagnostic test so that these doors can be opened for families and these children have access to the personalized medical treatments that are available today.

Rena Vanzo MS, LCGC Licensed & Certified Genetic Counselor,
Vice President, Clinical Services, Lineagen, Inc.

Read More: Early intervention gives therapies the best chance to succeed

CMA testing should be done at the earliest signs of developmental concern. Waiting can be harmful for these families because they can lose months of therapy and physicians can lose months of important treatment time for that child.

CMA genetic testing is appropriate for infants who have some sort of birth defect or clear developmental abnormalities all the way through individuals in their 50's, 60's or beyond. All of those individuals could benefit from a medical genetic CMA test.

But the window of opportunity when someone is young is so much greater. It's very important for these families to know early what path their child is on and have access to different therapies in different programs.

A genetic diagnosis provides access to therapy programs

Many states provide a zero-to-three years of age early intervention program, sometimes at no cost for the patient if, he or she qualifies. One thing many people don't know is that these states often have a list of genetic diagnoses that will automatically allow that child to qualify for those services. That can be really important for that child.

Genetic diagnosis can help pinpoint the best therapy

In addition, knowing early on about the presence of a genetic condition can give a doctor advance notice about therapies that are going to be more appropriate. For example, there is a genetic condition known as inversion duplication 15 syndrome. This is caused by aduplication on chromosome 15 that's diagnosable by CMA1.

Individuals with this condition have a very high risk of seizures and their seizures are actually treatable by certain medication, but those same seizures are exacerbated by a different type of anti-epileptic2.

It would be critical for a doctor to know in advance if their patient does start to seize that they don't want to use this family of anti-epileptic. They want to use this other family of anti-epileptic. That's critical knowledge that can save this family and this patient from a lot of unnecessary and difficult changes in the pharmacologic treatment for them.

1. Wang NJ, Liu D, Parokonny AS, Schanen NC. High-resolution molecular characterization of q13 rearrangements by array comparative genomic hybridization (array CGH) with detection of gene dosage. Am J Hum Genet. 2004 Aug;75(2):267-81.

2. Conant KD, Finucane B, Cleary N, Martin A, Muss C, Delany M, Murphy EK, Rabe O, Luchsinger K, Spence SJ, Schanen C, Devinsky O, Cook EH, LaSalle J,Reiter LT, Thibert RL. A survey of seizures and current treatments in 15q duplication syndrome. Epilepsia. 2014 Mar;55(3):396-402.

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CMA testing should be done at the earliest signs of developmental concern. Waiting can be stressful for these families and harmful for their child, because they can lose months of therapy and physicians can lose months of important treatment time for that child.
Rena Vanzo
MS, LCGC Licensed & Certified Genetic Counselor,
Vice President, Clinical Services, Lineagen, Inc.