Rare Disease Day 2022: Marfan Syndrome
28 February 2022
I’ve always been the tallest guy in the class. My dad was tall, my grandad was even taller so I always felt it was normal to be that tall until a doctor told me differently.

And so begins the story of Gianmarco and his father, a story about a rare disease, family inheritance and diagnostic odyssey.

Gianmarco and his father have Marfan syndrome (MFS), a syndrome that is caused by a mutation in a gene, FBN1, the one that makes fibrillin. This mutation results in abnormal connective tissue because the protein doesn’t fulfill its function and the greatest risk is to have problems like the enlargement of the aorta. About 75% of the time, the condition is inherited from a parent with the condition [1].

The odyssey for this family began with the grandfather at the beginning of 1900’s. The grandfather was diagnosed too late because at the time the syndrome was almost unknown, so the symptoms ended up in a report but no one gave him a diagnosis.

The diagnostic criteria of MFS were agreed upon internationally in 1996 [2].

Fulvio, Gianmarco’s father, didn’t know that he had inherited this syndrome even though some phenotypes, such as the length of his limbs and some heart and eye problems, could have created a suspicion for his doctors. During this period the diagnostic criteria were not yet ready.

In 2000, when Gianmarco was 6 years old, a pediatrician started investigating his phenotype because he had a friend, an orthopedist, who was working on MFS and he was told about the new criteria to diagnose this rare disease. Gianmarco at the time had just 2 peculiar characteristics of Marfan Syndrome: long limbs and a slight pectus deformity. The pediatrician started to do some tests.

No sooner had the tests begun than Fulvio was rushed into surgery because his aorta was abnormally enlarged.

I collapsed on my knees, I felt a very strong burning in my chest and I understood what it was but at that moment theoretically I had to be on a plane to go to Chile

After this episode, thanks to pediatrician advice, they were taken into the care of a geneticist to better understand what was happening. They were suggested to sequence their exome and they were discovered to have Marfan syndrome.

Gianmarco was lucky to be diagnosed while young, as Marfan syndrome can have life-threatening complications as those his father had.

With regular monitoring and modern treatments, he can now expect to live a normal life span: this is why an early and accurate genetic diagnosis is so important for rare diseases.

For the Rare Disease Day we are happy to share with you this story, we believe that is the time to bring genome interpretation to the next level, to finally end the diagnostic odyssey for millions of patients like Gianmarco and pave the way to new personalized treatments.

[1] “What Is Marfan Syndrome?”. NHLBI, NIH. October 1, 2010. Archived from the original on 6 May 2016. Retrieved 16 May 2016.1

[2] De Paepe A, Devereux RB, Dietz HC, Hennekam RC, Pyeritz RE (April 1996). “Revised diagnostic criteria for the Marfan syndrome”. American Journal of Medical Genetics. 62 (4): 417–426.