Table 1.

Clinical vignettes

Vignette 1: Marfan syndrome (FBN1)

Imagine that an eMERGE study doctor meets with you and explains that you have a variant in the FBN1 gene. This variant is related to risk of a disease called Marfan syndrome. People with Marfan syndrome tend to be tall and have long thin fingers and toes. They also may have scoliosis (a curved spine), an indentation or protrusion of their breast bone, or eye problems such as being nearsighted. The biggest health concern for people with Marfan syndrome is that the aorta, the large blood vessel that carries oxygen through the body, becomes too wide. If the aorta becomes too wide, it can rupture and lead to sudden death. The study doctor explains that there is a lot we can do to help. With appropriate care and surveillance, people with Marfan syndrome can expect to live long productive lives. We would look at your heart regularly using an echocardiogram (ultrasound for the heart). We may suggest medications to keep the aorta from widening. If the aorta becomes too wide, it may require surgery. We may recommend avoiding activities such as contact sports or weight lifting. Children who have Marfan syndrome can start seeing a specialist for monitoring of their heart. Most people with Marfan syndrome inherit the genetic change from a parent. Other close relatives may have this same genetic change. The doctor explains that your family members may wish to be tested to discover if they too have inherited the same risk factor.

Vignette 2: malignant hyperthermia (RYR1)

Imagine that the eMERGE study doctor meets with you and explains instead that you have a variant in the RYR1 gene. People with this variant are at risk for a condition called malignant hyperthermia, an abnormal reaction to certain medications used for general anesthesia during surgery. When they receive these medications, people with malignant hyperthermia have very high temperature, a fast heart rate, and breathing rate, and breakdown of skeletal muscles. They may die during surgery if not treated immediately. However, when we know that a person has this variant, we can let other doctors know to use different medications during surgery. People with RYR1 alterations may also be at increased risk of heat stroke, and may need to avoid excess activity in high heat. If you have this variant, Kaiser Permanente would put an alert in your medical record so that if you ever needed surgery the team would know right away to avoid certain medications. The study doctor explains that it is likely that you inherited this variant from one of your parents. If you have brothers, sisters, or children, they might also wish to be tested to see if they have inherited the same risk factor.