If you have a connective tissue condition or are seeking an evaluation for one, you know that you need to see a cardiologist to evaluate your heart, an orthopedist to evaluate your bones and joints, and an ophthalmologist to evaluate your eyes. But what is the role of the medical geneticist?
We asked Dr. Irman Forghani, medical geneticist, the most common questions we hear about the role of the medical geneticist and genetic testing.
Why is a medical geneticist important in the diagnosis and management of someone with Marfan, LDS, or VEDS?
Hereditary connective tissue disorders such as Marfan syndrome, Loeys-Dietz, and Vascular Ehlers-Danlos (VEDS), are rare conditions that involve various organs, in particular the heart, blood vessels, skin, joints, bone, eyes, and lungs. Affected individuals may not present with the well-described form of the disease, and if the physician is not familiar with these conditions or doesn’t collect required information, such as complete family history, diagnosis may be missed. Medical geneticists are experts in the diagnosis of these complex conditions.
As a geneticist with a particular interest in hereditary connective tissue disorders, I personally have seen patients with suggestive medical or family history who remained undiagnosed until the patient or a family member faced a serious complication of the condition. Medical geneticists are familiar with the various presentations of these disorders, can best evaluate the detailed medical and family history, and ensure the patients have the thorough physical exams that are essential in diagnosing. They know who can benefit from genetic testing.
A medical geneticist is not only trained to diagnose these rare conditions, but is also familiar with genetic testing and interpretation of DNA variants. In rare cases, the diagnosis may be made by clinical evaluations despite negative genetic test results. Although advancements in genetic technologies have made genetic testing accessible and more efficient, these technologies are not perfect yet; geneticists will consider further investigation tailored to each case to determine the diagnosis.
What should someone ask the medical geneticist at their first appointment?
Questions that a person should ask a geneticist at their first visit can vary, depending on why they have been referred to a geneticist. In general, geneticists start the discussion by giving an overview of what we know about the condition. These include clinical presentations and organ systems involved, the progression of clinical findings, best diagnostic approaches, possible outcomes of genetic tests, available treatments, and management recommendations.
Geneticists also provide genetic counseling regarding the chance of having these conditions if a person has an affected family member or the risk of passing these conditions to the next generation if they have a confirmed diagnosis. Patients of childbearing age with an actual diagnosis can ask about preconception diagnosis and testing and their family planning options. There are also active clinical trials for some of these conditions that a patient may be interested in getting information about.
If someone has a Marfan, Loeys-Dietz, or VEDS diagnosis, why should other people in their family see a geneticist or genetic counselor? Who needs genetic testing?
There is a 50% chance that an affected person passes the condition to her/his offspring; therefore, all the first degree relatives of an affected person should receive genetic counseling and testing. Many of these disorders are progressive in nature. The person who has the condition may not show any symptoms at the early stages of the condition, and symptoms emerge as they grow older. Early detection of these conditions is essential because, with proper management, we can prevent life-threatening complications or slow the condition’s progression.
Can family members with the same diagnosis have different medical journeys? What’s the genetic explanation for this?
Yes, in many genetic syndromes, the severity of the condition varies between affected individuals, even in family members who carry the exact same genetic defect. The cause or causes of variable presentation of a syndrome in different patients is not entirely understood and is thought to be due to other genetic, epigenetic, and environmental factors that can modify presentation of the condition.
If you have a clinical diagnosis, do you also need a genetic test?
The answer is Yes. Multiple genes and many different mutations are leading to these conditions. Having a particular DNA variant helps in better understanding the patient’s medical progression.
It also helps to identify potential pre-symptomatic individuals in the family. When we know the disease-causing DNA variations in a family, we know what to look for in the family members who may carry the gene defect, but they are still too young to present the symptoms.
In some conditions, like Loeys-Dietz syndrome, the specific genetic variation can give us information about the severity of the condition and may change the screening frequency.
In addition, these conditions have many overlapping symptoms. Until 2005, physicians did not recognize LDS and thought that it was a form of Marfan syndrome; however, we now know that although these syndromes have many overlapping phenotypes, they are two distinct syndromes with different genetic causes and management. A genetic test can differentiate these conditions when the clinical presentation is equivocal.
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Dr. Forghani is an Assistant Professor of Clinical Genetics within the Dr. John T. Macdonald Foundation Department of Human Genetics at the University of Miami Miller School of Medicine and medical geneticist at the University of Miami Hereditary Connective Tissue Disorders Clinic.