Conditions you may see in practice: Marfan syndrome

Throughout this course, we will be looking at examples of genetic conditions you may come across in pregnancy or neonatal care. One such autosomal dominant condition is Marfan syndrome, which is caused by pathogenic variants in the FBN1 gene.

This is a condition that affects a person’s connective tissue, particularly in the heart, eye and joints.

Connective tissue usually provides strength and flexibility to bones, muscles, ligaments, blood vessels and heart valves. In Marfan syndrome, a person’s connective tissue is not able to complete this function as it normally would.

The symptoms from Marfan syndrome that each person experiences are different and can vary between people in the same family, even with the same gene variant (this is known as variable expressivity).

If a person with Marfan syndrome plans a family, their chance of passing the condition on can be determined using a Punnett square. (If you need a refresher on Punnett squares, this animation from earlier in the course provides a helpful overview).

m – the FBN1 gene without any alterations (variants)
M- the FBN1 gene with a pathogenic variant

As you can see, there are four different combinations of genes that could be passed on, and 2 out of 4 of these options would result in the pregnancy inheriting the condition.

This means the chance of the couple having a child with Marfan syndrome is 1 in 2 or 50%. This chance applies to each pregnancy the couple may have.

Marfan syndrome and pregnancy

A woman with Marfan syndrome should have early access to both obstetric and genetic referral pathways. Although it is important to note that not all couples will want genetic counselling or intervention in the pregnancy and should be asked if they wish to be referred to the clinical genetics team.

When a genetic counsellor receives a referral for a couple where they carry an FBN1 gene pathogenic variant, they will obtain a copy of the genetic test report to ensure that the variant is definitely the cause of the condition. This is because we need to be certain about the effect of the variant, as pregnant people may use this information to decide whether to continue a pregnancy or not.

The genetic counsellor will also obtain a family history. This can also give insight into how much the condition has affected the family and becomes important in helping support the couple in their decision-making in the pregnancy.

The genetic counsellor will then discuss with the patient their thoughts and feelings in detail about having a baby with the condition and, if relevant, their genetic testing options. If a pregnancy is found to have a genetic condition, the genetic counsellor will then help support them in their choice of either gaining access to a termination, or continuing a pregnancy.

It is also important for all women who have an inherited cardiovascular condition to have an assessment in relation to their pregnancy to ensure their cardiac health is monitored correctly.

It is advised that women diagnosed with Marfan syndrome need regular screening of the aorta and review with Cardiology as the aorta can increase in size (dilate) during pregnancy.

Activity

Take a few minutes to have a look at other autosomal dominant disorders that you may come across in the pregnancy. Do you have an interesting fact you can share with the group of how one of these conditions may affect a pregnancy or birth?

The MedlinePlus and NHS are two useful websites that can assist you with this activity.

Want to learn more?

If you want to learn more about Marfan syndrome management in pregnancy, the following two articles provide a great overview:

• Regitz-Zagrosek V. et al 2018, ‘ESC Guidelines for the management of cardiovascular diseases during pregnancy: The Task Force for the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC)’.

• Goland S. and Elkayam U. 2017, ‘Pregnancy and Marfan syndrome’.