Genetics and Art: a series with Dr. Bassem Bejjani

Dr. Bejjani is a medical geneticist who has practiced in academic and private settings for more than 30 years and published around 100 peer-reviewed papers in the genetics and genomics field.  He is the Chief Medical Officer of Metis Genetics.  He is past Chair of the Washington State Arts Commission and Vice President of Caravan, an interfaith art organization.  He currently serves on the boards of WESTAF (Western States Art Federation) and The Henry Art Gallery at the University of Washington.  Dr. Bejjani will discuss the interplay between the worlds of genetics and art in this blog series. 

El Greco’s esthetic and Marfan syndrome

We will continue our series on genetics and art, and how genetics has appeared in art over time with a discussion of the artist “El Greco” and the appearance of features in his subjects that may be attributed to Marfan syndrome.

Doménikos Theotokópoulos, more commonly known as “El Greco” (The Greek) was born in Crete in 1541. He was a painter, sculptor, and architect of the Spanish Renaissance.  He trained and worked in Venice and Rome, then moved to Spain where, after a brief stay in Madrid, he relocated to Toledo in 1577 where he remained until his death in 1614.

El Greco’s work is unique.  While he does not belong to any specific school or art movement, his work shows the influence of the Renaissance masters and Byzantine iconic tradition.  He discarded the classic criteria of measure and proportions, and adopted a unique esthetic that eventually influenced many painters of the 20th century (Cézanne, Braque, Picasso, and many others).  Central to his esthetic is the unnatural elongation of the human body. This has been attributed alternatively to his defective vision, such as progressive astigmatism, or to his familiarity with individuals with Marfan syndrome.¹  Since many people appearing in El Greco’s paintings were inspired by people he met in real life², it has been suggested that the physical features of Marfan syndrome may have influenced his style.¹

Examples include the “Portrait of St. Sebastian” (1610-1614) (see Figure 1), and “The Adoration of the Shepherds” (1612-1614) where some of the classic features of Marfan syndrome can be identified in some, if not most subjects: tall and slender build, disproportionately long arms, legs and fingers, long and narrow head, posterior displacement of the eyes (enophthalmos), small lower jaw (micrognathia), and flat cheek bones (malar hypoplasia).

The incidence of Marfan syndrome is approximately 1 in 5,000 worldwide.  It is a genetic condition that is inherited in an autosomal dominant manner, which means that one copy of the altered gene in each cell is sufficient to cause the disorder.  About 25% of Marfan syndrome cases result from a new mutation (a de novo mutation) in the Fibrillin gene (FBN1). Therefore, in these cases, the individuals would have no history of the disorder in their family.³ Although 75% of individuals diagnosed with Marfan syndrome do have an affected parent, it is also possible for the family history to appear to be negative because of failure to recognize the disorder in the family, or the early death of a parent before a clinical diagnosis could be established.

Marfan syndrome is a condition that affects the connective tissue. Connective tissue is found throughout the body, therefore Marfan syndrome can affect many systems, often causing abnormalities in the heart, blood vessels, eyes, bones, and joints. The two main features of Marfan syndrome are vision problems caused by a dislocated lens, and defects in the aorta, the large blood vessel that distributes blood from the heart to the rest of the body.³

Individuals with Marfan syndrome are usually tall and slender, have elongated fingers and toes (arachnodactyly), loose joints, and have an arm span that is longer than their body height. Other common features include a long and narrow face, crowded teeth, and an abnormal curvature of the spine.³  These are the features that are evident in individuals in some of El Greco’s paintings.  It is thought that several famous figures may have had Marfan syndrome, including Abraham Lincoln and Peter Mayhew (the actor who played Chewbacca in Star Wars.⁴

It is important to correctly diagnose and monitor Marfan syndrome for proper medical management.  The most serious complication being potential issues with the aorta.  The aorta can weaken and stretch in Marfan, leading to an aneurysm. Stretching of the aorta may cause the aortic valve to leak, which can lead to a sudden tearing of the layers in the aorta wall (an aortic dissection). Aortic aneurysm and dissection are life-threatening.³

The features of Marfan syndrome can be recognized at any time between infancy and adulthood. Depending on the onset and the severity of the symptoms, Marfan syndrome can be fatal early in life. However, with proper treatment, many affected individuals have normal lifespans.³  This is why it is so important for individuals with potential features of Marfan syndrome to receive genetic counseling and testing.

Genetic testing for Marfan syndrome consists of sequencing of FBN1 to look for pathogenic sequence variants, and deletion/duplication analysis. The children of an individual with Marfan syndrome are at 50% risk of inheriting the FBN1 pathogenic variant. The penetrance of FBN1 pathogenic variants is reported to be 100%.  Therefore, children who inherit an FBN1 pathogenic variant from an affected parent will have Marfan syndrome, although the severity cannot be predicted.  Once an FBN1 pathogenic variant has been identified in an affected family member, prenatal testing for pregnancies at increased risk, and preimplantation genetic diagnosis are possible.⁵

El Greco did not have a medical and molecular genetic understanding of Marfan syndrome as we do today.  However, it is possible that he was attempting to document the features of the condition as far back as the 1500s.  This is yet another example of how genetics has appeared in art over human history.

References:

1.Kwoczyński J (2006) The figures in El Greco’s paintings have signs of Marfan’s syndrome. Kardiol Pol 64:1214–1220, discussion 1221-

2. Martínez-Lage, J.F., Piqueras, C. & Pérez-Espejo, M. The human body through the El Greco’s eyes. Childs Nerv Syst 30, 1471–1474 (2014).

3.  https://ghr.nlm.nih.gov/condition/marfan-syndrome

4. https://www.abc.net.au/news/2018-03-01/marfan-syndrome-genetic-disorder-chewbacca/9485060

5.  https://www.ncbi.nlm.nih.gov/books/NBK1335/